SARS-CoV-2 remains a threat to global health, especially in the light of new, more contagious variants capable of escaping vaccine-induced neutralizing antibodies (Cele et al., 2021; Tada et al., 2021; Tegally et al., 2021; Wibmer et al., 2021). Although vaccination may not prevent transmission, it is generally effective at preventing severe disease, primarily via eliciting neutralizing antibodies targeting the SARS-CoV-2 spike protein (Frater et al., 2021; Shinde et al., 2021; Tada et al., 2021). Risk factors for severe disease, especially in unvaccinated people, include old age (>65), underlying lung and heart disease; diabetes; and immune disorders such as those caused by HIV infection (Williamson et al., 2020). HIV has also been associated with increased morbidity and mortality (Bhaskaran et al., 2021; Western Cape Department of Health in collaboration with the National Institute for Communicable Diseases, South Africa, 2021), especially in patients with uncontrolled HIV viremia (Chanda et al., 2021) and in those with CD4 counts below 200 cells/µl, emphasizing the need for effective antiretroviral therapy (ART) (Karim et al., 2021). In addition, an inadequate immune response to COVID-19 is associated with prolonged SARS-CoV-2 infection and high intra-host mutation rates in both uncontrolled HIV and patients on immune-suppressing medication (Cele et al., 2022; McCormick et al., 2021). This highlights the importance of understanding the immune response to COVID-19 in patients with HIV, especially in the South African context, which has a high HIV prevalence (Kharsany et al., 2018) and SARS-CoV-2 attack rate (Tegally et al., 2021).

HIV affects the adaptive immune response by infecting CD4 T cells and reducing their numbers in circulation (Dalgleish et al., 1984; Westendorp et al., 1995). CD4 T follicular helper (Tfh) cells are a critical component of the germinal centre (GC) reaction as they assist the affinity maturation of their cognate B cell’s antigen receptor (BCR). The knock-on effects of HIV infection can therefore include hypergammaglobulinemia (Lane et al., 1983), depleted resting memory, and increased naïve B cell frequencies (Moir and Fauci, 2014). Interestingly, as with other inflammatory diseases (Freudenhammer et al., 2020), HIV is also associated with an increased prevalence of ‘tissue-like’ memory B cells in circulation (Ehrhardt et al., 2005; Knox et al., 2017; Moir and Fauci, 2014). These CD27-ve CD21-ve B cells resemble the EF constituent now often referred to as double negative (DN) B cells (Jenks et al., 2019; Jenks et al., 2020; Woodruff et al., 2020). These HIV-induced changes in the B cell compartment are likely to be responsible for the reduced vaccine efficacy and durability observed in people living with HIV (PLWH), including to novel SARS-CoV-2 vaccines (Hassold et al., 2022; Kernéis et al., 2014), and may contribute to prolonged viremia and increased viral mutation (Cele et al., 2022; Karim et al., 2021).

We, therefore, investigated the effect of HIV on the B cell response to SARS-CoV-2 infection, using a comprehensive B cell phenotyping approach and B cell baits to identify SARS-CoV-2-specific B cells. Blood samples were collected at weekly intervals from PLWH and HIV-ve study participants following positive COVID-19 diagnosis during the first wave of infections in a cohort of patients from Durban, South Africa (Karim et al., 2021). In this cohort of individuals with predominantly mild-moderate disease, the B cell response to SARS-CoV-2 infection is strikingly different in PLWH and characterized by reduced GC activity and a contrasting increase in EF activity.

We investigated the longitudinal dynamics of the B cell response to SARS-CoV-2 infection in PLWH compared to HIV-ve patients using a previously described COVID-19 cohort enrolled in Durban, South Africa, during the first wave of the pandemic in July 2020 (Karim et al., 2021). A total of 70 SARS-CoV-2 positive, confirmed by qPCR and serology, and 10 negative control participants were included in this study. Of the SARS-CoV-2-positive participants, 28 (40%) were PLWH, and 5 (18%) had detectable HIV in their plasma. SARS-CoV-2 infected participants were monitored weekly for five follow-up time points. Control participants were recruited at a single time point and were confirmed as SARS-CoV-2 negative by qPCR and serology and included two PLWH individuals. As some of the participants remained asymptomatic throughout the study, a timescale relating to days after positive diagnostic swab rather than symptom onset was used (days post-diagnostic swab), which has been shown to correlate well with symptom onset in the symptomatic patients from this cohort (Karim et al., 2021).

B cells were initially identified as CD19+ lymphocytes (Figure 1A), and the expression pattern of CD27 and CD38 was used to identify the canonical naïve, memory, and antibody-secreting cell (ASC) subsets (Glass et al., 2020). The ASC population was further differentiated into CD138+ plasma cells (PC) and CD138- plasmablasts (PB) (Glass et al., 2020). Considering all time points, HIV viremic participants had lower absolute B cell numbers, although this difference did not reach statistical significance. However, HIV-ve SARS-CoV-2 infected participants had significantly fewer naïve B cells and more memory B cells than SARS-CoV-2 infected PLWH and SARS-CoV-2 uninfected controls (Figure 1B; Moir and Fauci, 2014). The ASC response was significantly elevated at SARS-CoV-2 viremic time points in both patient groups, consistent with a robust ASC response to active infection (Figure 1C) but was not significantly different in PLWH. In addition, although the frequency of ASC at the earliest time point tended to be higher in the HIV-ve group, this was not statistically significant. Using the patient neutrophil-lymphocyte ratio (NLR) as a proxy of inflammation (Ciccullo et al., 2020; Fu et al., 2020; Karim et al., 2021), the frequency of ASC was found to be significantly higher at time points when the NLR ratio was above 3 (Figure 1D), suggesting an association between disease severity and ASC frequency. Finally, the PC:PB ratio was not significantly different between PLWH and HIV-ve patients at any time point, although there was a trend for a lower ratio in PLWH (Figure 1E). Taken together these data suggest that despite differences in canonical B cell phenotypes known to precede ASC maturation, PLWH mounted a similar ASC response against SARS-CoV-2 infection to HIV-ve participants.

Figure 1 with 1 supplement see all

Download asset Open asset

To further investigate the B cell response to SARS-CoV-2 in PLWH, we designed three B cell phenotyping flow cytometry panels, using markers specific for B cell maturation, activation, homing, and regulatory function (Figure 2A, C and D). Fresh PBMC from all participants were stained using all three panels separately and analysed using an unbiased approach combining FlowSOM and tSNE pipelines (van der Maaten, 2008; Van Gassen et al., 2015). This identified 11–12 distinct B cell clusters between the three phenotyping panels, with probable B cell phenotypes assigned based on the expression pattern of surface markers associated with each B cell cluster (Figure 2A, C and D). To uncover associations between HIV infection status or disease severity, an equal number of B cells for each disease severity category (ordinal scale 1–3 [OS1 to 3], Karim et al., 2021) were included, distributed equally between PLWH and HIV-ve controls. All comparisons in this figure were done with baseline samples. This allowed the relative abundance of each B cell cluster to be compared between the following clinical parameters: an ordinal disease scale (1–3), NLR as a measure of inflammation (Ciccullo et al., 2020; Fu et al., 2020; Karim et al., 2021), SARS-CoV-2 viral load, and HIV status.

Figure 2 with 3 supplements see all

Download asset Open asset

Using B cell panel 1 (Supplementary file 1, Figure 2A), distinct patterns of homing marker expression were observed. Two CD27+CD38++ ASC populations are identified, highlighted in red and purple (Figure 2A). The former also expressed high levels of CXCR3, the primary receptor for CXCL9, -10, -11, which facilitates homing to inflamed tissues (Onodera et al., 2012; Serre et al., 2012; Sutton et al., 2021), high levels of the extravasation marker CD62L+, and, uniquely, the activation/tissue residency marker CD69+. Therefore, this population is referred to as tissue homing and potentially indicates B cells which preferentially migrate to the diseased lung (Onodera et al., 2012; Serre et al., 2012; Sutton et al., 2021; Weisel et al., 2020). In line with this, tissue homing ASC are highly elevated in participants with the most severe disease (OS3), with elevated NLR, and with detectable SARS-CoV-2 viremia, as, to a lesser extent, are ASCs lacking this tissue homing phenotype (Figure 2A and B). In addition, a population of IgM^hi naïve B cells (highlighted in blue) was associated with severe disease, which co-expressed markers associated with GC homing (CXCR5 and CXCR4; Cyster and Allen, 2019). Strikingly, all three populations are elevated in HIV-ve participants but not in PLWH, as indicated in the final two columns of the heatmap. In PLWH, by contrast, disease severity was associated with an elevated population of B cells expressing a CD27-IgD- phenotype, corresponding to DN B cells (highlighted in grey), which lacked elevated expression of any of the homing markers measured. Several B cell subsets are elevated in asymptomatic subjects, including transitional B cells, as reported elsewhere (Woodruff et al., 2020) and a class switched memory (CSM) phenotype that expressed CXCR3, suggestive of differentiation into plasma blasts/cells (Muehlinghaus et al., 2005). As expected, in the control patients, the naïve B cell phenotype was predominantly IgD+ IgM- (brown), whereas the SARS-CoV-2 infected participants IgD+ naïve cells also expressed low levels of IgM+ (yellow; Figure 2B). Both naïve populations are high for CXCR5 and CXCR4, consistent with their requirement to gain entry to GC for affinity maturation (dark and light zones, respectively [Cyster and Allen, 2019]). Interestingly CCR6 was also upregulated in the SARS-CoV-2+ naïve B cells, suggestive of systemic B cell activation and transition of activated naïve B cells to pre-GC B cells (Reimer et al., 2017; Schwickert et al., 2011; Wiede et al., 2013). Together these data confirm that, as reported elsewhere (Woodruff et al., 2020), COVID-19 severity is associated with skewing of B cell phenotype and, for the first time, that this skewing is altered by concurrent HIV infection.

The association between disease severity and B cell phenotype was less apparent in data generated using the other two flow cytometry panels and, therefore not reported in the heatmaps (Figure 2C and D; Figure 2—figure supplements 2 and 3). However, distinct differences between PLHW and HIV-ve participants were also apparent. Panel 2, composed of maturation markers (Figure 2C), again suggests that ASC were less prevalent in PLWH than in HIV-ve participants, particularly CD138+ PC. In addition, CSM cells expressing CD69, consistent with activation, were elevated in HIV-ve participants but not PLWH. In contrast, two DN populations can be distinguished, differing by CD40 expression (purple and turquoise), both of which feed into an EF B cell maturation pathway (Jenks et al., 2019; Jenks et al., 2020; Woodruff et al., 2020), and both were elevated in PLWH. Likewise, an activated naïve (CD21^lo) population (orange) was also elevated in PLWH relative to HIV-ve participants. Two other naïve phenotypes were apparent, differing by their expression of CD40, of which the CD40-ve population appeared to be unique to the HIV-ve COVID-19+ participants (red population). Finally, two small transitional B cell populations were detectable, one of which, with a distinctive high IgD, CD21, and CD40 phenotype, was elevated in PLWH.

For panel 3, comprised of regulatory markers, the same reduced ASC response in PLWH was suggested (highlighted in blue), as the key B cell markers CD19, IgD, IgM, CD27, and CD38 are shared between all three panels. In this case, ASC are shown to express high levels of CD86, associated with B cell activation (Cyster and Allen, 2019). The same association between PLWH and DN B cells was also apparent (highlighted in orange), and which also display CD86 expression (Figure 2D). In addition, a small population of B cells expressing high levels of CD5 (CD5++) was elevated in PLWH. These cells co-express CD1d, consistent with regulatory B cells producing the critical regulatory cytokine IL-10 (Oleinika et al., 2018; Palmer et al., 2015; Yanaba et al., 2008). Another important regulatory molecule in B cells is PD-L1, which can limit T-cell help via engaging with PD-1 on the surface of Tfh cells in the GC (Khan et al., 2015). The expression of this marker was primarily associated with B cell subsets present in non-COVID-19 controls (Figure 2D, pink and grey), suggesting it is downregulated during SARS-CoV-2 infection. However, PD-L1 expression did not appear to be affected by HIV coinfection. Taken together, these unbiased analyses consistently show that the B cell response to SARS-CoV-2 is skewed in PLWH, associated with a reduction in ASC subsets, class switching, and markers of GC homing and with an increase of B cell phenotypes associated with EF maturation.

To drill down further, we next analysed the skewed B cell subsets of interest in longitudinal samples by Boolean gating. Unlike in the tSNE analysis, where downsampling was used to prevent bias analysis, all study subjects were included in these analyses. Consistent with the potential difference in GC activity and class switching observed above, we found that CD27+ IgD- switched memory (SM) B cells were significantly more frequent in HIV-ve COVID-19 patients than in PLWH (Figure 3A). Furthermore, the fraction of SM B cells expressing CD62L and CXCR5, allowing them to home the GC, was reduced in PLWH, particularly in individuals with viremic HIV (Figure 3B). Longitudinal analysis shows this population increases over time in both groups, consistent with a dynamic change associated with SARS-CoV-2 infection but is consistently lower in PLWH (Figure 3B). A similar trend was observed for CSM B cells, which were expanded in HIV-ve participants compared to controls but were significantly lower in viremic PLWH (Figure 3C). Interestingly, IgM-only memory B cells (Bautista et al., 2020) were significantly upregulated in all COVID-19 patient groups relative to the control group, but again this was reduced in the PLWH group. Although the precise function of this B cell subset is debated, it is believed they can achieve rapid PC differentiation, GC re-initiation, and IgM and IgG memory pool replenishment (Weill and Reynaud, 2020). Together these data suggest that concurrent HIV infection may cause a reduction in GC homing, class switching, and memory establishment after SARS-CoV-2 infection, which was generally exacerbated in individuals with viremic HIV.

Figure 3 with 1 supplement see all

Download asset Open asset

Next, given that the alternative to B cell maturation in the GC involves an EF route, DN B cells were examined in detail. The DN phenotype, also referred to as atypical B cells, forms part of an EF B cell response, which circumvents/pre-empts the GC reaction resulting in a rapid but short-lived PB response that facilitates rapid antibody production (Jenks et al., 2019; Jenks et al., 2020; Song et al., 2022; Woodruff et al., 2020). Both activated DN B cells, commonly referred to as the DN2 cells, and activated naïve phenotypes, contribute to the EF response (Jenks et al., 2019) and are identified as CD21^lo CXCR5^lo CD95+ subsets (Figure 4A; Figure 4—figure supplement 1). Multiple studies have described the expansion of DN2 B cells in association with severe COVID disease (Chen et al., 2020; Kaneko et al., 2020; Woodruff et al., 2020), but not in relation to HIV. Here, DN2 and activated naïve B cells were identified by expression of CD95, a known marker of activation on B cells (Freudenhammer et al., 2020; Glass et al., 2020; Jenks et al., 2020; Le Gallo et al., 2017). The DN2 phenotype studied here lacked both CD21 and CXCR5 expression (R²=0.89, p<0.0001; Figure 4—figure supplement 1A), with a positive correlation for CD95 and CD11c expression (R²=0.66, p<0.0001; Figure 4—figure supplement 1B). Both EF-associated B cell phenotypes were significantly more frequent in the SARS-CoV-2 infected PLWH relative to the HIV-ve group, irrespective of HIV viremia in the case of DN2 (Figure 4B; Figure 4—figure supplement 2A (i)). In addition, both subsets change in frequency over the course of infection, expanding from time point 2 (days 7–13) and remaining significantly expanded compared to HIV-ve participants until after time point 4 (days 21–27), after which they contract to the same level (Figure 4C; Figure 4—figure supplement 2B). The dynamic nature of this EF response strongly suggests that it emerges during SARS-CoV-2 infection and does not represent a pre-existing difference associated with HIV. Interestingly though, a direct association with SARS-CoV-2 viral load was evident only in the PLWH with suppressed HIV, whereas for HIV viremic individuals, the DN2 phenotype associated better with disease severity and inflammation (Figure 4—figure supplement 1C), which has been associated with chronic HIV infection (Austin et al., 2019). This is further supported by the fact that the frequency of DN2 and, to a lesser extent, activated naïve B cells, correlates with the RBD antibody titre in PLWH, particularly those with detectable HIV (Figure 4D; Figure 4—figure supplement 2C). In addition, the frequency of these populations was associated with increased clinical disease severity and NLR in PLWH but not in HIV-ve participants (Figure 4C; Figure 4—figure supplement 2B). Indeed, the lack of an EF response in HIV-ve participants is highlighted by the absence of DN populations even in subjects in OS3 and with elevated NLRs. These data are highly consistent with the data shown in Figure 3 and suggest that the B cell response to SARS-CoV-2 infection in PLWH is associated with reduced GC maturation and increased EF activity.

Figure 4 with 2 supplements see all

Download asset Open asset

Having observed elevated PD-L1 in non-COVID controls, we examined the expression of this marker longitudinally in conjunction with CD5 to examine regulatory B cell frequency (Figure 5A; Figure 5—figure supplement 1; Catalán et al., 2021; Khan et al., 2015; Sun et al., 2019). This revealed a clear shift in PD-L1 expression on naïve B cells longitudinally, which was very low at baseline and increased to the range observed in controls by the final time point (Figure 5B). Similar frequencies and longitudinal trends were observed in both PLWH and HIV-ve participants, suggesting this is a consistent feature of the acute B cell response to SARS-CoV-2 infection. However, PD-L1 CD5+ B cells are significantly more frequent in HIV viremic individuals (Figure 5A). PD-L1 expression plays an integral part in the GC response and maintains the relatively unstable Tfh lineage (Khan et al., 2015). Interestingly, the frequency of total Tfh tended to be higher in PLWH, reaching significance at time points 2 and 5 (Figure 5C). Although the frequency of SARS-CoV-2-specific Tfh was not measured, these data again point to potential impairment of the GC response in PLWH, which is dependent on the crosstalk between B cells and Tfh governed, in part, by the interaction between PD-L1 expressed on B cells and PD-1 on Tfh (Khan et al., 2015; Sun et al., 2019).

Figure 5 with 1 supplement see all

Download asset Open asset

Finally, as the data presented above was based on bulk B cell phenotyping, we examined a subset of informative markers on SARS-CoV-2-specific B cells using recombinant SARS-CoV-2 spike and RBD proteins conjugated to fluorescent streptavidin as baits (Goel et al., 2021;; Figure 6A; Supplementary file 2). B cells staining with both spike and RBD baits were quantified at baseline and 3 months, revealing robust SARS-CoV-2-specific memory B cell populations in all individuals, which did not significantly wane by 3 months and were not different in frequency between PLHW and HIV-ve participants (Figure 6B). Interestingly, in this subset of participants, the degree of CSM was not significantly different between groups and tended to increase over time in both. However, spike-specific memory B cells from PLWH tended to express higher levels of CXCR3 (Figure 6C), particularly at month 3, a marker associated with homing to inflamed tissue (Onodera et al., 2012; Serre et al., 2012; Sutton et al., 2021). Finally, a significantly higher proportion of spike-specific B cells from PLWH displayed a DN2 phenotype, confirming the increased EF activity towards SARS-CoV-2 in these individuals suggested by the bulk phenotyping.

Figure 6

Download asset Open asset

Using longitudinal samples from the first wave of infection in South Africa, we found that HIV coinfection significantly impacted the B cell response to SARS-CoV-2. Overall, these data show that the B cell response in PLWH is skewed towards an EF route and away from GC maturation. This is demonstrated by several observations, including elevated DN2 and activated naïve B cells in PLWH, consistent with EF maturation; mirrored by reduced class switching of memory B cells and reduced expression of markers CXCR5 and CD62L allowing B cells to home to the GC. This general reduction in GC homing capacity of B cells has been associated with PLWH previously (Cagigi et al., 2008). In addition, as an effective GC reaction requires tight regulation of the Tfh response, observed differences in PD-L1 expression on B cells and Tfh frequency in PLWH are likely to hamper B cell maturation via this pathway. Importantly, the skewing towards EF B cell maturation in PLWH correlated with anti-RBD antibody titre in these individuals and was confirmed on SARS-CoV-2 spike-specific B cells.

Multiple studies have characterized the B cell response to COVID-19 in HIV-ve individuals and observed a positive correlation between disease severity and an elevated ASC response (Kaneko et al., 2020; Karim et al., 2021; Woodruff et al., 2020). Furthermore, an EF B cell response has been associated with severe COVID-19 and predicts poor clinical outcomes, and severe COVID-19 cases have been characterized by poor GC formation in secondary lymphoid organs (Chen et al., 2020; Kaneko et al., 2020; Woodruff et al., 2020). However, the impact of HIV coinfection on the B cell response and these associations is unknown. Here, we find that the ASC response is associated with disease severity in both HIV-ve participants and PLWH, although the effect appears more robust in HIV-ve participants. More detailed phenotyping of the ASC supports this, as CD138+ PC and ASC with a tissue homing and activated phenotype (CXCR3+ CD69+ in panel 1 and CD86+ in panel 2) were more strongly associated with SARS-CoV-2 infection in HIV-ve participants. In contrast, the association between disease severity and EF activity was uniquely observed in PLWH. The absence of EF activity in HIV-ve participants is not at odds with published literature, as no individuals with severe COVID-19 were included in this study (Kaneko et al., 2020; Woodruff et al., 2020). Therefore, the association between HIV and EF B cells is not driven by disease severity.

Although not previously observed for COVID-19, the skewing of B cells towards an EF response in PLWH makes biological sense. Jenks et al. achieved successful ex vivo stimulation of DN2 B cells in response to pro-inflammatory cytokines IFNγ, TNFa, and IL-21; and TLR 7 and 9 stimulation, with CD40L having little effect, thus proposing a potentially extrafollicular maturation capacity of these cells, independent of T cell help (Jenks et al., 2019; Jenks et al., 2020). More recently Song et al. provided elegant in vivo evidence for peri-follicular interaction of DN2 B cells with Tfh, but not Th1 cells prior to GC formation and demonstrate that CD40L stimulation was integral to trigger their initial activation. Their model therefore suggests a peri-follicular, extra-GC maturation pathway requiring only an initial Tfh interaction (Song et al., 2022). HIV induces a pro-inflammatory state (Connolly et al., 2005; Roff et al., 2014), making B cells more prone to EF maturation; and HIV viremia is known to induce a DN2 response (Amu et al., 2013; Ferreira et al., 2013). This link may explain the association between DN2 frequency and inflammation in PLWH, as measured by the NLR ratio. On the other hand, since HIV depletes CD4 T cells, it also impairs GC activity, including BCR somatic hypermutation, class switching, and, ultimately, the ASC response (Okoye and Picker, 2013; Pallikkuth et al., 2012; Perreau et al., 2013), consistent with the trends observed. Likewise, HIV alters the B cell compartment by affecting the frequencies of naïve and memory B cells (Moir and Fauci, 2014), again agreeing with the differences in the frequency of naïve and memory B cells observed in this study.

The downstream consequence of skewed B cell maturation in PLWH is unclear from this study. However, the EF response relies primarily on the existing germline and memory BCR repertoire, whereas the GC response allows for honing of the BCR repertoire through somatic hypermutation and stringent affinity selection of BCR clones to generate high-affinity long-term ASC and memory responses (Jenks et al., 2020; Kaneko et al., 2020). Therefore, the loss of GC B cell maturation could result in a less effective B cell response to infection in PLWH and potentially a greater susceptibility to infection by variants. Sette and Crotty, 2021, demonstrated that the antibody response to COVID-19 parent strain derives from the germline BCR repertoire without the need for extensive hypermutation. This might explain why HIV status did not seem to affect the antibody response during the first wave of infections (Snyman et al., 2021). In contrast, the antibody response to the second wave of infections was affected by HIV status, with PLWH mounting less effective IgG responses to the Beta variant (Hwa et al., 2022). Therefore, the skewed EF B cell response could explain the less effective response against new variants. Indeed, multiple studies have revealed B cell maturation and expanded somatic hypermutation months after primary infection in COVID-19 patients without HIV (Gaebler et al., 2021; Wang et al., 2021) and have highlighted the importance of antibody affinity maturation (Chen et al., 2020; Muecksch et al., 2021) and class switching (Zohar et al., 2020) to reduce disease severity and gain improved efficacy against new variants. This might also explain the lack of effective clearance of SARS-CoV-2 in HIV viremic individuals and might be a mechanism for intra-host evolution in patients with uncontrolled HIV (Cele et al., 2022). Further work is needed to understand how the skewed B cell response to natural infection impacts long-term memory and the ability to adapt to new viral variants. It will also be essential to understand the impact of vaccination on the B cell memory compartment.

All data generated or analyzed during this study are included in the manuscript and Source data 1.

1. 1. Amu S
   2. Ruffin N
   3. Rethi B
   4. Chiodi F

   (2013) Impairment of B-cell functions during HIV-1 infection

   AIDS 27:2323–2334.

   https://doi.org/10.1097/QAD.0b013e328361a427

   • PubMed
   • Google Scholar
2. 1. Austin JW
   2. Buckner CM
   3. Kardava L
   4. Wang W
   5. Zhang X
   6. Melson VA
   7. Swanson RG
   8. Martins AJ
   9. Zhou JQ
   10. Hoehn KB
   11. Fisk JN
   12. Dimopoulos Y
   13. Chassiakos A
   14. O’Dell S
   15. Smelkinson MG
   16. Seamon CA
   17. Kwan RW
   18. Sneller MC
   19. Pittaluga S
   20. Doria-Rose NA
   21. McDermott A
   22. Li Y
   23. Chun T-W
   24. Kleinstein SH
   25. Tsang JS
   26. Petrovas C
   27. Moir S

   (2019) Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation

   Science Translational Medicine 11:eaax0904.

   https://doi.org/10.1126/scitranslmed.aax0904

   • PubMed
   • Google Scholar
3. 1. Bautista D
   2. Vásquez C
   3. Ayala-Ramírez P
   4. Téllez-Sosa J
   5. Godoy-Lozano E
   6. Martínez-Barnetche J
   7. Franco M
   8. Angel J

   (2020) Differential expression of igm and igd discriminates two subpopulations of human circulating igm+igd+CD27+ B cells that differ phenotypically, functionally, and genetically

   Frontiers in Immunology 11:736.

   https://doi.org/10.3389/fimmu.2020.00736

   • Google Scholar
4. 1. Bhaskaran K
   2. Rentsch CT
   3. MacKenna B
   4. Schultze A
   5. Mehrkar A
   6. Bates CJ
   7. Eggo RM
   8. Morton CE
   9. Bacon SCJ
   10. Inglesby P
   11. Douglas IJ
   12. Walker AJ
   13. McDonald HI
   14. Cockburn J
   15. Williamson EJ
   16. Evans D
   17. Forbes HJ
   18. Curtis HJ
   19. Hulme WJ
   20. Parry J
   21. Hester F
   22. Harper S
   23. Evans SJW
   24. Smeeth L
   25. Goldacre B

   (2021) HIV infection and COVID-19 death: a population-based cohort analysis of UK primary care data and linked national death registrations within the opensafely platform

   The Lancet. HIV 8:e24–e32.

   https://doi.org/10.1016/S2352-3018(20)30305-2

   • PubMed
   • Google Scholar
5. 1. Cagigi A
   2. Mowafi F
   3. Phuong Dang LV
   4. Tenner-Racz K
   5. Atlas A
   6. Grutzmeier S
   7. Racz P
   8. Chiodi F
   9. Nilsson A

   (2008) Altered expression of the receptor-ligand pair CXCR5/CXCL13 in B cells during chronic HIV-1 infection

   Blood 112:4401–4410.

   https://doi.org/10.1182/blood-2008-02-140426

   • PubMed
   • Google Scholar
6. 1. Catalán D
   2. Mansilla MA
   3. Ferrier A
   4. Soto L
   5. Oleinika K
   6. Aguillón JC
   7. Aravena O

   (2021) Immunosuppressive mechanisms of regulatory B cells

   Frontiers in Immunology 12:611795.

   https://doi.org/10.3389/fimmu.2021.611795

   • PubMed
   • Google Scholar
7. 1. Cele S
   2. Gazy I
   3. Jackson L
   4. Hwa S-H
   5. Tegally H
   6. Lustig G
   7. Giandhari J
   8. Pillay S
   9. Wilkinson E
   10. Naidoo Y
   11. Karim F
   12. Ganga Y
   13. Khan K
   14. Bernstein M
   15. Balazs AB
   16. Gosnell BI
   17. Hanekom W
   18. Moosa M-YS
   19. Network for Genomic Surveillance in South Africa
   20. COMMIT-KZN Team
   21. Lessells RJ
   22. de Oliveira T
   23. Sigal A

   (2021) Escape of SARS-cov-2 501Y.V2 from neutralization by convalescent plasma

   Nature 593:142–146.

   https://doi.org/10.1038/s41586-021-03471-w

   • PubMed
   • Google Scholar
8. 1. Cele S
   2. Karim F
   3. Lustig G
   4. San JE
   5. Hermanus T
   6. Tegally H
   7. Snyman J
   8. Moyo-Gwete T
   9. Wilkinson E
   10. Bernstein M
   11. Khan K
   12. Hwa S-H
   13. Tilles SW
   14. Singh L
   15. Giandhari J
   16. Mthabela N
   17. Mazibuko M
   18. Ganga Y
   19. Gosnell BI
   20. Karim SSA
   21. Hanekom W
   22. Van Voorhis WC
   23. Ndung’u T
   24. COMMIT-KZN Team
   25. Lessells RJ
   26. Moore PL
   27. Moosa M-YS
   28. de Oliveira T
   29. Sigal A

   (2022) SARS-cov-2 prolonged infection during advanced HIV disease evolves extensive immune escape

   Cell Host & Microbe 30:154–162.

   https://doi.org/10.1016/j.chom.2022.01.005

   • PubMed
   • Google Scholar
9. 1. Chanda D
   2. Minchella PA
   3. Kampamba D
   4. Itoh M
   5. Hines JZ
   6. Fwoloshi S
   7. Boyd MA
   8. Hamusonde K
   9. Chirwa L
   10. Nikoi K
   11. Chirwa R
   12. Siwingwa M
   13. Sivile S
   14. Zyambo KD
   15. Mweemba A
   16. Mbewe N
   17. Mutengo KH
   18. Malama K
   19. Agolory S
   20. Mulenga LB

   (2021) COVID-19 severity and COVID-19-associated deaths among hospitalized patients with HIV infection-Zambia, march-december 2020

   MMWR. Morbidity and Mortality Weekly Report 70:807–810.

   https://doi.org/10.15585/mmwr.mm7022a2

   • PubMed
   • Google Scholar
10. 1. Chen Y
    2. Zuiani A
    3. Fischinger S
    4. Mullur J
    5. Atyeo C
    6. Travers M
    7. Lelis FJN
    8. Pullen KM
    9. Martin H
    10. Tong P
    11. Gautam A
    12. Habibi S
    13. Bensko J
    14. Gakpo D
    15. Feldman J
    16. Hauser BM
    17. Caradonna TM
    18. Cai Y
    19. Burke JS
    20. Lin J
    21. Lederer JA
    22. Lam EC
    23. Lavine CL
    24. Seaman MS
    25. Chen B
    26. Schmidt AG
    27. Balazs AB
    28. Lauffenburger DA
    29. Alter G
    30. Wesemann DR

    (2020) Quick COVID-19 healers sustain anti-SARS-cov-2 antibody production

    Cell 183:1496–1507.

    https://doi.org/10.1016/j.cell.2020.10.051

    • PubMed
    • Google Scholar
11. 1. Ciccullo A
    2. Borghetti A
    3. Zileri Dal Verme L
    4. Tosoni A
    5. Lombardi F
    6. Garcovich M
    7. Biscetti F
    8. Montalto M
    9. Cauda R
    10. Di Giambenedetto S
    11. GEMELLI AGAINST COVID Group

    (2020) Neutrophil-to-lymphocyte ratio and clinical outcome in COVID-19: a report from the italian front line

    International Journal of Antimicrobial Agents 56:106017.

    https://doi.org/10.1016/j.ijantimicag.2020.106017

    • PubMed
    • Google Scholar
12. 1. Connolly NC
    2. Riddler SA
    3. Rinaldo CR

    (2005)

    Proinflammatory cytokines in HIV disease-a review and rationale for new therapeutic approaches

    AIDS Reviews 7:168–180.

    • PubMed
    • Google Scholar
13. 1. Cyster JG
    2. Allen CDC

    (2019) B cell responses: cell interaction dynamics and decisions

    Cell 177:524–540.

    https://doi.org/10.1016/j.cell.2019.03.016

    • PubMed
    • Google Scholar
14. 1. Dalgleish AG
    2. Beverley PC
    3. Clapham PR
    4. Crawford DH
    5. Greaves MF
    6. Weiss RA

    (1984) The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus

    Nature 312:763–767.

    https://doi.org/10.1038/312763a0

    • PubMed
    • Google Scholar
15. 1. Ehrhardt GRA
    2. Hsu JT
    3. Gartland L
    4. Leu C-M
    5. Zhang S
    6. Davis RS
    7. Cooper MD

    (2005) Expression of the immunoregulatory molecule fcrh4 defines a distinctive tissue-based population of memory B cells

    The Journal of Experimental Medicine 202:783–791.

    https://doi.org/10.1084/jem.20050879

    • PubMed
    • Google Scholar
16. 1. Ferreira CB
    2. Merino-Mansilla A
    3. Llano A
    4. Pérez I
    5. Crespo I
    6. Llinas L
    7. Garcia F
    8. Gatell JM
    9. Yuste E
    10. Sanchez-Merino V

    (2013) Evolution of broadly cross-reactive HIV-1-neutralizing activity: therapy-associated decline, positive association with detectable viremia, and partial restoration of B-cell subpopulations

    Journal of Virology 87:12227–12236.

    https://doi.org/10.1128/JVI.02155-13

    • PubMed
    • Google Scholar
17. 1. Frater J
    2. Ewer KJ
    3. Ogbe A
    4. Pace M
    5. Adele S
    6. Adland E
    7. Alagaratnam J
    8. Aley PK
    9. Ali M
    10. Ansari MA
    11. Bara A
    12. Bittaye M
    13. Broadhead S
    14. Brown A
    15. Brown H
    16. Cappuccini F
    17. Cooney E
    18. Dejnirattisai W
    19. Dold C
    20. Fairhead C
    21. Fok H
    22. Folegatti PM
    23. Fowler J
    24. Gibbs C
    25. Goodman AL
    26. Jenkin D
    27. Jones M
    28. Makinson R
    29. Marchevsky NG
    30. Mujadidi YF
    31. Nguyen H
    32. Parolini L
    33. Petersen C
    34. Plested E
    35. Pollock KM
    36. Ramasamy MN
    37. Rhead S
    38. Robinson H
    39. Robinson N
    40. Rongkard P
    41. Ryan F
    42. Serrano S
    43. Tipoe T
    44. Voysey M
    45. Waters A
    46. Zacharopoulou P
    47. Barnes E
    48. Dunachie S
    49. Goulder P
    50. Klenerman P
    51. Screaton GR
    52. Winston A
    53. Hill AVS
    54. Gilbert SC
    55. Pollard AJ
    56. Fidler S
    57. Fox J
    58. Lambe T
    59. Oxford COVID Vaccine Trial Group

    (2021) Safety and immunogenicity of the chadox1 ncov-19 (AZD1222) vaccine against SARS-cov-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial

    The Lancet. HIV 8:e474–e485.

    https://doi.org/10.1016/S2352-3018(21)00103-X

    • PubMed
    • Google Scholar
18. 1. Freudenhammer M
    2. Voll RE
    3. Binder SC
    4. Keller B
    5. Warnatz K

    (2020) Naive- and memory-like cd21^low B cell subsets share core phenotypic and signaling characteristics in systemic autoimmune disorders

    Journal of Immunology 205:2016–2025.

    https://doi.org/10.4049/jimmunol.2000343

    • PubMed
    • Google Scholar
19. 1. Fu J
    2. Kong J
    3. Wang W
    4. Wu M
    5. Yao L
    6. Wang Z
    7. Jin J
    8. Wu D
    9. Yu X

    (2020) The clinical implication of dynamic neutrophil to lymphocyte ratio and D-dimer in COVID-19: a retrospective study in suzhou China

    Thrombosis Research 192:3–8.

    https://doi.org/10.1016/j.thromres.2020.05.006

    • PubMed
    • Google Scholar
20. 1. Gaebler C
    2. Wang Z
    3. Lorenzi JCC
    4. Muecksch F
    5. Finkin S
    6. Tokuyama M
    7. Cho A
    8. Jankovic M
    9. Schaefer-Babajew D
    10. Oliveira TY
    11. Cipolla M
    12. Viant C
    13. Barnes CO
    14. Bram Y
    15. Breton G
    16. Hägglöf T
    17. Mendoza P
    18. Hurley A
    19. Turroja M
    20. Gordon K
    21. Millard KG
    22. Ramos V
    23. Schmidt F
    24. Weisblum Y
    25. Jha D
    26. Tankelevich M
    27. Martinez-Delgado G
    28. Yee J
    29. Patel R
    30. Dizon J
    31. Unson-O’Brien C
    32. Shimeliovich I
    33. Robbiani DF
    34. Zhao Z
    35. Gazumyan A
    36. Schwartz RE
    37. Hatziioannou T
    38. Bjorkman PJ
    39. Mehandru S
    40. Bieniasz PD
    41. Caskey M
    42. Nussenzweig MC

    (2021) Evolution of antibody immunity to SARS-cov-2

    Nature 591:639–644.

    https://doi.org/10.1038/s41586-021-03207-w

    • PubMed
    • Google Scholar
21. 1. Glass DR
    2. Tsai AG
    3. Oliveria JP
    4. Hartmann FJ
    5. Kimmey SC
    6. Calderon AA
    7. Borges L
    8. Glass MC
    9. Wagar LE
    10. Davis MM
    11. Bendall SC

    (2020) An integrated multi-omic single-cell atlas of human B cell identity

    Immunity 53:217–232.

    https://doi.org/10.1016/j.immuni.2020.06.013

    • PubMed
    • Google Scholar
22. 1. Goel RR
    2. Apostolidis SA
    3. Painter MM
    4. Mathew D
    5. Pattekar A
    6. Kuthuru O
    7. Gouma S
    8. Hicks P
    9. Meng W
    10. Rosenfeld AM
    11. Dysinger S
    12. Lundgreen KA
    13. Kuri-Cervantes L
    14. Adamski S
    15. Hicks A
    16. Korte S
    17. Oldridge DA
    18. Baxter AE
    19. Giles JR
    20. Weirick ME
    21. McAllister CM
    22. Dougherty J
    23. Long S
    24. D’Andrea K
    25. Hamilton JT
    26. Betts MR
    27. Luning Prak ET
    28. Bates P
    29. Hensley SE
    30. Greenplate AR
    31. Wherry EJ

    (2021) Distinct antibody and memory B cell responses in SARS-cov-2 naïve and recovered individuals following mrna vaccination

    Science Immunology 6:58.

    https://doi.org/10.1126/sciimmunol.abi6950

    • PubMed
    • Google Scholar
23. 1. Hassold N
    2. Brichler S
    3. Ouedraogo E
    4. Leclerc D
    5. Carroue S
    6. Gater Y
    7. Alloui C
    8. Carbonnelle E
    9. Bouchaud O
    10. Mechai F
    11. Cordel H
    12. Delagreverie H

    (2022) Impaired antibody response to COVID-19 vaccination in advanced HIV infection

    AIDS 36:F1–F5.

    https://doi.org/10.1097/QAD.0000000000003166

    • PubMed
    • Google Scholar
24. 1. Hwa S-H
    2. Snyman J
    3. Bernstein M
    4. Ganga Y
    5. Cele S
    6. Muema D
    7. Tan CW
    8. Khan K
    9. Karim F
    10. Hanekom W
    11. Bernstein L
    12. Kaufmann SHE
    13. Wang L-F
    14. Ndung’u T
    15. Sigal A

    (2022) Association Between Human Immunodeficiency Virus Viremia and Compromised Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2 Beta Variant

    The Journal of Infectious Diseases jiac343.

    https://doi.org/10.1093/infdis/jiac343

    • PubMed
    • Google Scholar
25. 1. Jenks SA
    2. Cashman KS
    3. Woodruff MC
    4. Lee FE-H
    5. Sanz I

    (2019) Extrafollicular responses in humans and SLE

    Immunological Reviews 288:136–148.

    https://doi.org/10.1111/imr.12741

    • PubMed
    • Google Scholar
26. 1. Jenks SA
    2. Cashman KS
    3. Zumaquero E
    4. Marigorta UM
    5. Patel AV
    6. Wang X
    7. Tomar D
    8. Woodruff MC
    9. Simon Z
    10. Bugrovsky R
    11. Blalock EL
    12. Scharer CD
    13. Tipton CM
    14. Wei C
    15. Lim SS
    16. Petri M
    17. Niewold TB
    18. Anolik JH
    19. Gibson G
    20. Eun-Hyung Lee F
    21. Boss JM
    22. Lund FE
    23. Sanz I

    (2020) Distinct effector B cells induced by unregulated toll-like receptor 7 contribute to pathogenic responses in systemic lupus erythematosus

    Immunity 52:203.

    https://doi.org/10.1016/j.immuni.2019.12.005

    • PubMed
    • Google Scholar
27. 1. Kaneko N
    2. Kuo H-H
    3. Boucau J
    4. Farmer JR
    5. Allard-Chamard H
    6. Mahajan VS
    7. Piechocka-Trocha A
    8. Lefteri K
    9. Osborn M
    10. Bals J
    11. Bartsch YC
    12. Bonheur N
    13. Caradonna TM
    14. Chevalier J
    15. Chowdhury F
    16. Diefenbach TJ
    17. Einkauf K
    18. Fallon J
    19. Feldman J
    20. Finn KK
    21. Garcia-Broncano P
    22. Hartana CA
    23. Hauser BM
    24. Jiang C
    25. Kaplonek P
    26. Karpell M
    27. Koscher EC
    28. Lian X
    29. Liu H
    30. Liu J
    31. Ly NL
    32. Michell AR
    33. Rassadkina Y
    34. Seiger K
    35. Sessa L
    36. Shin S
    37. Singh N
    38. Sun W
    39. Sun X
    40. Ticheli HJ
    41. Waring MT
    42. Zhu AL
    43. Alter G
    44. Li JZ
    45. Lingwood D
    46. Schmidt AG
    47. Lichterfeld M
    48. Walker BD
    49. Yu XG
    50. Padera RF
    51. Pillai S
    52. Massachusetts Consortium on Pathogen Readiness Specimen Working Group

    (2020) Loss of bcl-6-expressing T follicular helper cells and germinal centers in COVID-19

    Cell 183:143–157.

    https://doi.org/10.1016/j.cell.2020.08.025

    • PubMed
    • Google Scholar
28. 1. Karim F
    2. Gazy I
    3. Cele S
    4. Zungu Y
    5. Krause R
    6. Bernstein M
    7. Khan K
    8. Ganga Y
    9. Rodel H
    10. Mthabela N
    11. Mazibuko M
    12. Muema D
    13. Ramjit D
    14. Ndung’u T
    15. Hanekom W
    16. Gosnell B
    17. Lessells RJ
    18. Wong EB
    19. de Oliveira T
    20. Moosa M-YS
    21. Lustig G
    22. Leslie A
    23. Kløverpris H
    24. Sigal A
    25. COMMIT-KZN Team

    (2021) HIV status alters disease severity and immune cell responses in beta variant SARS-cov-2 infection wave

    eLife 10:e67397.

    https://doi.org/10.7554/eLife.67397

    • PubMed
    • Google Scholar
29. 1. Kernéis S
    2. Launay O
    3. Turbelin C
    4. Batteux F
    5. Hanslik T
    6. Boëlle P-Y

    (2014) Long-term immune responses to vaccination in HIV-infected patients: a systematic review and meta-analysis

    Clinical Infectious Diseases 58:1130–1139.

    https://doi.org/10.1093/cid/cit937

    • PubMed
    • Google Scholar
30. 1. Khan AR
    2. Hams E
    3. Floudas A
    4. Sparwasser T
    5. Weaver CT
    6. Fallon PG

    (2015) PD-l1hi B cells are critical regulators of humoral immunity

    Nature Communications 6:5997.

    https://doi.org/10.1038/ncomms6997

    • PubMed
    • Google Scholar
31. 1. Kharsany ABM
    2. Cawood C
    3. Khanyile D
    4. Lewis L
    5. Grobler A
    6. Puren A
    7. Govender K
    8. George G
    9. Beckett S
    10. Samsunder N
    11. Madurai S
    12. Toledo C
    13. Chipeta Z
    14. Glenshaw M
    15. Hersey S
    16. Abdool Karim Q

    (2018) Community-based HIV prevalence in kwazulu-natal, south africa: results of a cross-sectional household survey

    The Lancet. HIV 5:e427–e437.

    https://doi.org/10.1016/S2352-3018(18)30104-8

    • PubMed
    • Google Scholar
32. 1. Knox JJ
    2. Buggert M
    3. Kardava L
    4. Seaton KE
    5. Eller MA
    6. Canaday DH
    7. Robb ML
    8. Ostrowski MA
    9. Deeks SG
    10. Slifka MK
    11. Tomaras GD
    12. Moir S
    13. Moody MA
    14. Betts MR

    (2017) T-bet+ B cells are induced by human viral infections and dominate the HIV gp140 response

    JCI Insight 2:92943.

    https://doi.org/10.1172/jci.insight.92943

    • PubMed
    • Google Scholar
33. 1. Lane HC
    2. Masur H
    3. Edgar LC
    4. Whalen G
    5. Rook AH
    6. Fauci AS

    (1983) Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome

    The New England Journal of Medicine 309:453–458.

    https://doi.org/10.1056/NEJM198308253090803

    • PubMed
    • Google Scholar
34. 1. Le Gallo M
    2. Poissonnier A
    3. Blanco P
    4. Legembre P

    (2017) CD95/fas, non-apoptotic signaling pathways, and kinases

    Frontiers in Immunology 8:1216.

    https://doi.org/10.3389/fimmu.2017.01216

    • PubMed
    • Google Scholar
35. 1. McCormick KD
    2. Jacobs JL
    3. Mellors JW

    (2021) The emerging plasticity of SARS-cov-2

    Science 371:1306–1308.

    https://doi.org/10.1126/science.abg4493

    • PubMed
    • Google Scholar
36. 1. Moir S
    2. Fauci AS

    (2014) B-cell exhaustion in HIV infection: the role of immune activation

    Current Opinion in HIV and AIDS 9:472–477.

    https://doi.org/10.1097/COH.0000000000000092

    • PubMed
    • Google Scholar
37. 1. Muecksch F
    2. Weisblum Y
    3. Barnes CO
    4. Schmidt F
    5. Schaefer-Babajew D
    6. Wang Z
    7. C Lorenzi JC
    8. Flyak AI
    9. DeLaitsch AT
    10. Huey-Tubman KE
    11. Hou S
    12. Schiffer CA
    13. Gaebler C
    14. Da Silva J
    15. Poston D
    16. Finkin S
    17. Cho A
    18. Cipolla M
    19. Oliveira TY
    20. Millard KG
    21. Ramos V
    22. Gazumyan A
    23. Rutkowska M
    24. Caskey M
    25. Nussenzweig MC
    26. Bjorkman PJ
    27. Hatziioannou T
    28. Bieniasz PD

    (2021) Affinity maturation of SARS-cov-2 neutralizing antibodies confers potency, breadth, and resilience to viral escape mutations

    Immunity 54:1853–1868.

    https://doi.org/10.1016/j.immuni.2021.07.008

    • PubMed
    • Google Scholar
38. 1. Muehlinghaus G
    2. Cigliano L
    3. Huehn S
    4. Peddinghaus A
    5. Leyendeckers H
    6. Hauser AE
    7. Hiepe F
    8. Radbruch A
    9. Arce S
    10. Manz RA

    (2005) Regulation of CXCR3 and CXCR4 expression during terminal differentiation of memory B cells into plasma cells

    Blood 105:3965–3971.

    https://doi.org/10.1182/blood-2004-08-2992

    • PubMed
    • Google Scholar
39. 1. Okoye AA
    2. Picker LJ

    (2013) Cd4 (+) T-cell depletion in HIV infection: mechanisms of immunological failure

    Immunological Reviews 254:54–64.

    https://doi.org/10.1111/imr.12066

    • PubMed
    • Google Scholar
40. 1. Oleinika K
    2. Rosser EC
    3. Matei DE
    4. Nistala K
    5. Bosma A
    6. Drozdov I
    7. Mauri C

    (2018) CD1d-dependent immune suppression mediated by regulatory B cells through modulations of inkt cells

    Nature Communications 9:684.

    https://doi.org/10.1038/s41467-018-02911-y

    • PubMed
    • Google Scholar
41. 1. Onodera T
    2. Takahashi Y
    3. Yokoi Y
    4. Ato M
    5. Kodama Y
    6. Hachimura S
    7. Kurosaki T
    8. Kobayashi K

    (2012) Memory B cells in the lung participate in protective humoral immune responses to pulmonary influenza virus reinfection

    PNAS 109:2485–2490.

    https://doi.org/10.1073/pnas.1115369109

    • PubMed
    • Google Scholar
42. 1. Pallikkuth S
    2. Parmigiani A
    3. Silva SY
    4. George VK
    5. Fischl M
    6. Pahwa R
    7. Pahwa S

    (2012) Impaired peripheral blood T-follicular helper cell function in HIV-infected nonresponders to the 2009 H1N1/09 vaccine

    Blood 120:985–993.

    https://doi.org/10.1182/blood-2011-12-396648

    • PubMed
    • Google Scholar
43. 1. Palmer VL
    2. Nganga VK
    3. Rothermund ME
    4. Perry GA
    5. Swanson PC

    (2015) Cd1d regulates B cell development but not B cell accumulation and IL10 production in mice with pathologic CD5(+) B cell expansion

    BMC Immunology 16:66.

    https://doi.org/10.1186/s12865-015-0130-z

    • PubMed
    • Google Scholar
44. 1. Perreau M
    2. Savoye A-L
    3. De Crignis E
    4. Corpataux J-M
    5. Cubas R
    6. Haddad EK
    7. De Leval L
    8. Graziosi C
    9. Pantaleo G

    (2013) Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production

    The Journal of Experimental Medicine 210:143–156.

    https://doi.org/10.1084/jem.20121932

    • PubMed
    • Google Scholar
45. 1. Reimer D
    2. Lee AY
    3. Bannan J
    4. Fromm P
    5. Kara EE
    6. Comerford I
    7. McColl S
    8. Wiede F
    9. Mielenz D
    10. Körner H

    (2017) Early CCR6 expression on B cells modulates germinal centre kinetics and efficient antibody responses

    Immunology and Cell Biology 95:33–41.

    https://doi.org/10.1038/icb.2016.68

    • PubMed
    • Google Scholar
46. 1. Roff SR
    2. Noon-Song EN
    3. Yamamoto JK

    (2014) The significance of interferon-γ in HIV-1 pathogenesis, therapy, and prophylaxis

    Frontiers in Immunology 4:498.

    https://doi.org/10.3389/fimmu.2013.00498

    • PubMed
    • Google Scholar
47. 1. Schwickert TA
    2. Victora GD
    3. Fooksman DR
    4. Kamphorst AO
    5. Mugnier MR
    6. Gitlin AD
    7. Dustin ML
    8. Nussenzweig MC

    (2011) A dynamic T cell-limited checkpoint regulates affinity-dependent B cell entry into the germinal center

    The Journal of Experimental Medicine 208:1243–1252.

    https://doi.org/10.1084/jem.20102477

    • PubMed
    • Google Scholar
48. 1. Serre K
    2. Cunningham AF
    3. Coughlan RE
    4. Lino AC
    5. Rot A
    6. Hub E
    7. Moser K
    8. Manz R
    9. Ferraro A
    10. Bird R
    11. Toellner K-M
    12. Demengeot J
    13. MacLennan ICM
    14. Mohr E

    (2012) Cd8 T cells induce T-bet-dependent migration toward CXCR3 ligands by differentiated B cells produced during responses to alum-protein vaccines

    Blood 120:4552–4559.

    https://doi.org/10.1182/blood-2012-03-417733

    • PubMed
    • Google Scholar
49. 1. Sette A
    2. Crotty S

    (2021) Adaptive immunity to SARS-cov-2 and COVID-19

    Cell 184:861–880.

    https://doi.org/10.1016/j.cell.2021.01.007

    • PubMed
    • Google Scholar
50. 1. Shinde V
    2. Bhikha S
    3. Hoosain Z
    4. Archary M
    5. Bhorat Q
    6. Fairlie L
    7. Lalloo U
    8. Masilela MSL
    9. Moodley D
    10. Hanley S
    11. Fouche L
    12. Louw C
    13. Tameris M
    14. Singh N
    15. Goga A
    16. Dheda K
    17. Grobbelaar C
    18. Kruger G
    19. Carrim-Ganey N
    20. Baillie V
    21. de Oliveira T
    22. Lombard Koen A
    23. Lombaard JJ
    24. Mngqibisa R
    25. Bhorat AE
    26. Benadé G
    27. Lalloo N
    28. Pitsi A
    29. Vollgraaff P-L
    30. Luabeya A
    31. Esmail A
    32. Petrick FG
    33. Oommen-Jose A
    34. Foulkes S
    35. Ahmed K
    36. Thombrayil A
    37. Fries L
    38. Cloney-Clark S
    39. Zhu M
    40. Bennett C
    41. Albert G
    42. Faust E
    43. Plested JS
    44. Robertson A
    45. Neal S
    46. Cho I
    47. Glenn GM
    48. Dubovsky F
    49. Madhi SA
    50. 2019nCoV-501 Study Group

    (2021) Efficacy of NVX-cov2373 covid-19 vaccine against the B.1.351 variant

    The New England Journal of Medicine 384:1899–1909.

    https://doi.org/10.1056/NEJMoa2103055

    • PubMed
    • Google Scholar
51. 1. Snyman J
    2. Hwa SH
    3. Krause R
    4. Muema D
    5. Reddy T
    6. Ganga Y
    7. Team CK

    (2021) Similar antibody responses against SARS-cov-2 in HIV uninfected and infected individuals on antiretroviral therapy during the first south african infection wave

    Clinical Infectious Diseases 1:ciab758.

    https://doi.org/10.1093/cid/ciab758

    • Google Scholar
52. 1. Song W
    2. Antao OQ
    3. Condiff E
    4. Sanchez GM
    5. Chernova I
    6. Zembrzuski K
    7. Steach H
    8. Rubtsova K
    9. Angeletti D
    10. Lemenze A
    11. Laidlaw BJ
    12. Craft J
    13. Weinstein JS

    (2022) Development of tbet- and cd11c-expressing B cells in a viral infection requires T follicular helper cells outside of germinal centers

    Immunity 55:290–307.

    https://doi.org/10.1016/j.immuni.2022.01.002

    • PubMed
    • Google Scholar
53. 1. Sun X
    2. Zhang T
    3. Li M
    4. Yin L
    5. Xue J

    (2019) Immunosuppressive B cells expressing PD-1/PD-L1 in solid tumors: A mini review

    QJM 1:hcz162.

    https://doi.org/10.1093/qjmed/hcz162

    • PubMed
    • Google Scholar
54. 1. Sutton HJ
    2. Aye R
    3. Idris AH
    4. Vistein R
    5. Nduati E
    6. Kai O
    7. Mwacharo J
    8. Li X
    9. Gao X
    10. Andrews TD
    11. Koutsakos M
    12. Nguyen THO
    13. Nekrasov M
    14. Milburn P
    15. Eltahla A
    16. Berry AA
    17. Kc N
    18. Chakravarty S
    19. Sim BKL
    20. Wheatley AK
    21. Kent SJ
    22. Hoffman SL
    23. Lyke KE
    24. Bejon P
    25. Luciani F
    26. Kedzierska K
    27. Seder RA
    28. Ndungu FM
    29. Cockburn IA

    (2021) Atypical B cells are part of an alternative lineage of B cells that participates in responses to vaccination and infection in humans

    Cell Reports 34:108684.

    https://doi.org/10.1016/j.celrep.2020.108684

    • PubMed
    • Google Scholar
55. Preprint

    1. Tada T
    2. Zhou H
    3. Samanovic MI
    4. Dcosta BM
    5. Cornelius A
    6. Mulligan MJ
    7. Landau NR

    (2021) Comparison of Neutralizing Antibody Titers Elicited by MRNA and Adenoviral Vector Vaccine against SARS-CoV-2 Variants

    bioRxiv.

    https://doi.org/10.1101/2021.07.19.452771

    • Google Scholar
56. 1. Tegally H
    2. Wilkinson E
    3. Giovanetti M
    4. Iranzadeh A
    5. Fonseca V
    6. Giandhari J
    7. Doolabh D
    8. Pillay S
    9. San EJ
    10. Msomi N
    11. Mlisana K
    12. von Gottberg A
    13. Walaza S
    14. Allam M
    15. Ismail A
    16. Mohale T
    17. Glass AJ
    18. Engelbrecht S
    19. Van Zyl G
    20. Preiser W
    21. Petruccione F
    22. Sigal A
    23. Hardie D
    24. Marais G
    25. Hsiao N-Y
    26. Korsman S
    27. Davies M-A
    28. Tyers L
    29. Mudau I
    30. York D
    31. Maslo C
    32. Goedhals D
    33. Abrahams S
    34. Laguda-Akingba O
    35. Alisoltani-Dehkordi A
    36. Godzik A
    37. Wibmer CK
    38. Sewell BT
    39. Lourenço J
    40. Alcantara LCJ
    41. Kosakovsky Pond SL
    42. Weaver S
    43. Martin D
    44. Lessells RJ
    45. Bhiman JN
    46. Williamson C
    47. de Oliveira T

    (2021) Detection of a SARS-cov-2 variant of concern in south africa

    Nature 592:438–443.

    https://doi.org/10.1038/s41586-021-03402-9

    • PubMed
    • Google Scholar
57. 1. van der Maaten LHG

    (2008)

    Visualizing data using t-SNE

    Journal of Machine Learning Research 9:2579–2605.

    • Google Scholar
58. 1. Van Gassen S
    2. Callebaut B
    3. Van Helden MJ
    4. Lambrecht BN
    5. Demeester P
    6. Dhaene T
    7. Saeys Y

    (2015) FlowSOM: using self-organizing maps for visualization and interpretation of cytometry data

    Cytometry. Part A 87:636–645.

    https://doi.org/10.1002/cyto.a.22625

    • PubMed
    • Google Scholar
59. 1. Wang Z
    2. Schmidt F
    3. Weisblum Y
    4. Muecksch F
    5. Barnes CO
    6. Finkin S
    7. Schaefer-Babajew D
    8. Cipolla M
    9. Gaebler C
    10. Lieberman JA
    11. Oliveira TY
    12. Yang Z
    13. Abernathy ME
    14. Huey-Tubman KE
    15. Hurley A
    16. Turroja M
    17. West KA
    18. Gordon K
    19. Millard KG
    20. Ramos V
    21. Da Silva J
    22. Xu J
    23. Colbert RA
    24. Patel R
    25. Dizon J
    26. Unson-O’Brien C
    27. Shimeliovich I
    28. Gazumyan A
    29. Caskey M
    30. Bjorkman PJ
    31. Casellas R
    32. Hatziioannou T
    33. Bieniasz PD
    34. Nussenzweig MC

    (2021) Mrna vaccine-elicited antibodies to SARS-cov-2 and circulating variants

    Nature 592:616–622.

    https://doi.org/10.1038/s41586-021-03324-6

    • PubMed
    • Google Scholar
60. 1. Weill JC
    2. Reynaud CA

    (2020) Igm memory B cells: specific effectors of innate-like and adaptive responses

    Current Opinion in Immunology 63:1–6.

    https://doi.org/10.1016/j.coi.2019.09.003

    • PubMed
    • Google Scholar
61. 1. Weisel NM
    2. Weisel FJ
    3. Farber DL
    4. Borghesi LA
    5. Shen Y
    6. Ma W
    7. Luning Prak ET
    8. Shlomchik MJ

    (2020) Comprehensive analyses of B-cell compartments across the human body reveal novel subsets and a gut-resident memory phenotype

    Blood 136:2774–2785.

    https://doi.org/10.1182/blood.2019002782

    • PubMed
    • Google Scholar
62. 1. Westendorp MO
    2. Frank R
    3. Ochsenbauer C
    4. Stricker K
    5. Dhein J
    6. Walczak H
    7. Debatin KM
    8. Krammer PH

    (1995) Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120

    Nature 375:497–500.

    https://doi.org/10.1038/375497a0

    • PubMed
    • Google Scholar
63. 1. Western Cape Department of Health in collaboration with the National Institute for Communicable Diseases, South Africa

    (2021) Risk factors for coronavirus disease 2019 (COVID-19) death in a population cohort study from the western cape province, south africa

    Clinical Infectious Diseases 73:e2005–e2015.

    https://doi.org/10.1093/cid/ciaa1198

    • PubMed
    • Google Scholar
64. 1. Wibmer CK
    2. Ayres F
    3. Hermanus T
    4. Madzivhandila M
    5. Kgagudi P
    6. Oosthuysen B
    7. Lambson BE
    8. de Oliveira T
    9. Vermeulen M
    10. van der Berg K
    11. Rossouw T
    12. Boswell M
    13. Ueckermann V
    14. Meiring S
    15. von Gottberg A
    16. Cohen C
    17. Morris L
    18. Bhiman JN
    19. Moore PL

    (2021) SARS-cov-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma

    Nature Medicine 27:622–625.

    https://doi.org/10.1038/s41591-021-01285-x

    • PubMed
    • Google Scholar
65. 1. Wiede F
    2. Fromm PD
    3. Comerford I
    4. Kara E
    5. Bannan J
    6. Schuh W
    7. Ranasinghe C
    8. Tarlinton D
    9. Winkler T
    10. McColl SR
    11. Körner H

    (2013) Ccr6 is transiently upregulated on B cells after activation and modulates the germinal center reaction in the mouse

    Immunology and Cell Biology 91:335–339.

    https://doi.org/10.1038/icb.2013.14

    • PubMed
    • Google Scholar
66. 1. Williamson EJ
    2. Walker AJ
    3. Bhaskaran K
    4. Bacon S
    5. Bates C
    6. Morton CE
    7. Curtis HJ
    8. Mehrkar A
    9. Evans D
    10. Inglesby P
    11. Cockburn J
    12. McDonald HI
    13. MacKenna B
    14. Tomlinson L
    15. Douglas IJ
    16. Rentsch CT
    17. Mathur R
    18. Wong AYS
    19. Grieve R
    20. Harrison D
    21. Forbes H
    22. Schultze A
    23. Croker R
    24. Parry J
    25. Hester F
    26. Harper S
    27. Perera R
    28. Evans SJW
    29. Smeeth L
    30. Goldacre B

    (2020) Factors associated with COVID-19-related death using opensafely

    Nature 584:430–436.

    https://doi.org/10.1038/s41586-020-2521-4

    • PubMed
    • Google Scholar
67. 1. Woodruff MC
    2. Ramonell RP
    3. Nguyen DC
    4. Cashman KS
    5. Saini AS
    6. Haddad NS
    7. Ley AM
    8. Kyu S
    9. Howell JC
    10. Ozturk T
    11. Lee S
    12. Suryadevara N
    13. Case JB
    14. Bugrovsky R
    15. Chen W
    16. Estrada J
    17. Morrison-Porter A
    18. Derrico A
    19. Anam FA
    20. Sharma M
    21. Wu HM
    22. Le SN
    23. Jenks SA
    24. Tipton CM
    25. Staitieh B
    26. Daiss JL
    27. Ghosn E
    28. Diamond MS
    29. Carnahan RH
    30. Crowe JE Jr
    31. Hu WT
    32. Lee FE-H
    33. Sanz I

    (2020) Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19

    Nature Immunology 21:1506–1516.

    https://doi.org/10.1038/s41590-020-00814-z

    • PubMed
    • Google Scholar
68. 1. Yanaba K
    2. Bouaziz JD
    3. Haas KM
    4. Poe JC
    5. Fujimoto M
    6. Tedder TF

    (2008) A regulatory B cell subset with a unique cd1dhicd5+ phenotype controls T cell-dependent inflammatory responses

    Immunity 28:639–650.

    https://doi.org/10.1016/j.immuni.2008.03.017

    • PubMed
    • Google Scholar
69. 1. Zohar T
    2. Loos C
    3. Fischinger S
    4. Atyeo C
    5. Wang C
    6. Slein MD
    7. Burke J
    8. Yu J
    9. Feldman J
    10. Hauser BM
    11. Caradonna T
    12. Schmidt AG
    13. Cai Y
    14. Streeck H
    15. Ryan ET
    16. Barouch DH
    17. Charles RC
    18. Lauffenburger DA
    19. Alter G

    (2020) Compromised humoral functional evolution tracks with SARS-cov-2 mortality

    Cell 183:1508–1519.

    https://doi.org/10.1016/j.cell.2020.10.052

    • PubMed
    • Google Scholar

Author details

1. Robert Krause

   1. Africa Health Research Institute, Durban, South Africa
   2. School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa

   Contribution

   Conceptualization, Formal analysis, Investigation, Methodology, Writing - original draft, Writing – review and editing

   For correspondence

   robert.krause@ahri.org

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0003-1558-0397

2. Jumari Snyman

   1. Africa Health Research Institute, Durban, South Africa
   2. School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa
   3. HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu Natal, Durban, South Africa

   Contribution

   Investigation, Methodology, Writing – review and editing

   Competing interests

   No competing interests declared

3. Hwa Shi-Hsia

   1. Africa Health Research Institute, Durban, South Africa
   2. Division of Infection and Immunity, University College London, London, United Kingdom

   Contribution

   Investigation, Methodology, Writing – review and editing

   Competing interests

   No competing interests declared

4. Daniel Muema

   1. Africa Health Research Institute, Durban, South Africa
   2. School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa
   3. HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu Natal, Durban, South Africa

   Contribution

   Writing – review and editing

   Competing interests

   No competing interests declared

5. Farina Karim

   1. Africa Health Research Institute, Durban, South Africa
   2. School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa

   Contribution

   Project administration, Resources

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0001-9698-016X

6. Yashica Ganga

   Africa Health Research Institute, Durban, South Africa

   Contribution

   Project administration, Methodology, Writing – review and editing

   Competing interests

   No competing interests declared

7. Abigail Ngoepe

   Africa Health Research Institute, Durban, South Africa

   Contribution

   Project administration, Methodology, Writing – review and editing

   Competing interests

   No competing interests declared

8. Yenzekile Zungu

   1. Africa Health Research Institute, Durban, South Africa
   2. School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa

   Contribution

   Methodology, Writing – review and editing

   Competing interests

   No competing interests declared

9. Inbal Gazy

   1. School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa
   2. KwaZulu-Natal Research Innovation and Sequencing Platform, Durban, South Africa

   Contribution

   Methodology, Writing – review and editing

   Competing interests

   No competing interests declared

10. Mallory Bernstein

    Africa Health Research Institute, Durban, South Africa

    Contribution

    Project administration, Data curation, Writing – review and editing

    Competing interests

    No competing interests declared

11. Khadija Khan

    1. Africa Health Research Institute, Durban, South Africa
    2. School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa

    Contribution

    Project administration, Resources

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0001-7565-7400

12. Matilda Mazibuko

    Africa Health Research Institute, Durban, South Africa

    Contribution

    Project administration, Resources

    Competing interests

    No competing interests declared

13. Ntombifuthi Mthabela

    Africa Health Research Institute, Durban, South Africa

    Contribution

    Project administration, Resources

    Competing interests

    No competing interests declared

14. Dirhona Ramjit

    Africa Health Research Institute, Durban, South Africa

    Contribution

    Project administration, Resources

    Competing interests

    No competing interests declared

15. COMMIT-KZN Team

    Contribution

    Project administration, Resources

    Competing interests

    No competing interests declared

    1. Moherndran Archary, Department of Paediatrics and Child Health, University of KwaZulu-Natal, Durban, South Africa
    2. Kaylesh J Dullabh, Department of Cardiothoracic Surgery, University of KwaZulu-Nata, Durban, South Africa
    3. Jennifer Giandhari, KwaZulu-Natal Research Innovation and Sequencing Platform, Durban, South Africa
    4. Philip Goulder, Africa Health Research Institute and Department of Paediatrics, Durban, South Africa
    5. Guy Harling, Africa Health Research Institute and the Institute for Global Health, University College London, London, United Kingdom
    6. Rohen Harrichandparsad, Department of Neurosurgery, University of KwaZulu-Natal, Durban, South Africa
    7. Kobus Herbst, Africa Health Research Institute and the South African Population Research Infrastructure Network, Durban, South Africa
    8. Prakash Jeena, Department of Paediatrics and Child Health, University of KwaZulu-Natal, Durban, South Africa
    9. Thandeka Khoza, Africa Health Research Institute, Durban, South Africa
    10. Nigel Klein, Africa Health Research Institute and the Institute of Child Health, University College London, London, United Kingdom
    11. Rajhmun Madansein, Department of Cardiothoracic Surgery, University of KwaZulu-Nata, Durban, South Africa
    12. Mohlopheni Marakalala, Africa Health Research Institute and Division of Infection and Immunity, University College London, London, United Kingdom
    13. Mosa Moshabela, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
    14. Kogie Naidoo, Centre for the AIDS Programme of Research in South Africa, Durban, South Africa
    15. Zaza Ndhlovu, Africa Health Research Institute and the Ragon Institute of MGH, MIT and Harvard, Durban, South Africa
    16. Kennedy Nyamande, Department of Pulmonology and Critical Care, University of KwaZulu-Natal, Durban, South Africa
    17. Nesri Padayatchi, Centre for the AIDS Programme of Research in South Africa, Durban, South Africa
    18. Vinod Patel, Vinod Patel, Department of Neurology, University of KwaZulu-Natal, Durban, South Africa
    19. Theresa Smit, Africa Health Research Institute, Durban, South Africa
    20. Adrie Steyn, Africa Health Research Institute and Division of Infectious Diseases, University of Alabama, Birmingham, United States

16. Oliver Limbo

    International AIDS Vaccine Initiative, New York, United States

    Contribution

    Methodology, Resources, Validation

    Competing interests

    No competing interests declared

17. Joseph Jardine

    International AIDS Vaccine Initiative, New York, United States

    Contribution

    Methodology, Resources, Validation

    Competing interests

    No competing interests declared

18. Devin Sok

    International AIDS Vaccine Initiative, New York, United States

    Contribution

    Methodology, Resources, Validation

    Competing interests

    No competing interests declared

19. Ian A Wilson

    The Scripps Research Institute, La Jolla, United States

    Contribution

    Methodology, Resources, Validation

    Competing interests

    No competing interests declared

20. Willem Hanekom

    1. Africa Health Research Institute, Durban, South Africa
    2. Division of Infection and Immunity, University College London, London, United Kingdom

    Contribution

    Project administration, Funding acquisition, Writing – review and editing

    Competing interests

    Reviewing editor, eLife

21. Alex Sigal

    1. Africa Health Research Institute, Durban, South Africa
    2. School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa
    3. Max Planck Institute for Infection Biology, Berlin, Germany
    4. Centre for the AIDS Programme of Research in South Africa, Durban, South Africa

    Contribution

    Funding acquisition, Writing – review and editing

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0001-8571-2004

22. Henrik Kløverpris

    1. Africa Health Research Institute, Durban, South Africa
    2. Division of Infection and Immunity, University College London, London, United Kingdom
    3. Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark

    Contribution

    Project administration, Writing – review and editing, Funding acquisition

    Competing interests

    No competing interests declared

23. Thumbi Ndung'u

    1. Africa Health Research Institute, Durban, South Africa
    2. School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa
    3. HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu Natal, Durban, South Africa
    4. Division of Infection and Immunity, University College London, London, United Kingdom
    5. Max Planck Institute for Infection Biology, Berlin, Germany

    Contribution

    Writing – review and editing, Funding acquisition

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0003-2962-3992

24. Alasdair Leslie

    1. Africa Health Research Institute, Durban, South Africa
    2. Division of Infection and Immunity, University College London, London, United Kingdom

    Contribution

    Conceptualization, Supervision, Funding acquisition, Writing – review and editing

    Competing interests

    No competing interests declared

• 897

  views

• 193

  downloads

• 10

  citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.