COVID-19: Boosting in the age of Omicron
A third dose of the inactivated vaccine CoronaVac fails to stimulate the production of neutralizing antibodies which target the Omicron variant.
- Africa Health Research Institute, South Africa
Nowadays, most people who get sick with COVID-19 will have a stuffy or runny nose, a sore throat, a cough and a headache, sometimes accompanied by fatigue or mental fog. While unpleasant, these symptoms are not as dangerous as lung damage and breathing difficulties, which were common earlier in the pandemic. The inflection point took place in late 2021 and early 2022, closely linked to the emergence of Omicron subvariants which infect the upper parts of the respiratory tract better than the lower regions, mostly sparing severe infection of the lung. In conjunction, people gained extensive immunity through vaccination, previous infections, or a combination of both (Sigal, 2022).
Neutralizing antibodies, which are designed to block a specific virus from entering cells, are a major component of this immunity. COVID-19 vaccines aim to make the immune system produce these molecules, with the level of neutralizing antibodies released after immunization being strongly correlated with vaccine efficacy against symptomatic disease (Khoury et al., 2021). However, the amount of these protective antibodies decreases over time and additional ‘booster doses’, which complement the initial two-dose vaccination course, have been the main strategy used to counter this waning immunity. Yet Omicron subvariants have also evolved to evade neutralizing antibodies that could successfully deactivate earlier versions of SARS-CoV-2 (Cele et al., 2022).
Most current COVID-19 vaccines are designed based on one of several platforms; these include mRNA technology (as for the BNT162b2 vaccine by Pfizer), or using a whole inactivated virus (like CoronaVac, from the Chinese company Sinovac Biotech). Nations can either make their own vaccines or import them from abroad, and a variety of plausible reasons exist in favor of local manufacture, from national prestige to lower costs. Dependence on import can also be challenging if trading partners hold back doses to prioritize their own populations, or if the product poorly matches local needs, for example by requiring frozen storage. However, considering which type of vaccine works best should be an important consideration at this stage of the pandemic.
CoronaVac is currently used extensively in China, and it is also widely exported to countries such as Indonesia, Brazil, Pakistan or Turkey (Mallapaty, 2021). The consensus is that two CoronaVac doses prevent about 50% of vaccinees from getting sick, with a higher protection against severe disease that is maintained even against Omicron. Vaccine effectiveness against Omicron, however, is only about 25% for mild or moderate disease in people aged 20–59 (McMenamin et al., 2022; World Health Organization, 2021). This decrease in protection matches results showing that in a group of 30 individuals triple vaccinated with CoronaVac, only one person produced a neutralizing antibody response above the detection limit against Omicron (Cheng et al., 2022). More work is thus needed to confirm these findings, and to better characterise the immune response triggered by CoronaVac. Now, in eLife, Jianmin Jiang, Huakun Lv and colleagues – including Hangjie Zhang and Qianhui Hua as joint first authors – report that a third CoronaVac dose elicits neutralizing antibodies against the original strain of SARS-CoV-2, but not against Omicron (Zhang et al., 2023).
The team (who are based at various Centers for Disease Control and Prevention across China, Ningbo University, and Xiamen University) tracked neutralizing antibody responses in volunteers from the Zhejiang Province. They examined the immune response of over 1,000 individuals who had received one or two doses of CoronaVac, while also monitoring antibody production in 90 adults who received three CoronaVac injections during the study period.
Zhang et al. found that antibody responses had waned six months after second vaccination, and that it had become undetectable in most vaccinated individuals after a year. A third injection substantially increased the levels of neutralizing antibodies against an ancestral strain of SARS-CoV-2, as well as the Delta variant. However, Omicron neutralization remained low even after the third dose. Boosting with CoronaVac may therefore still protect against severe disease, but these results suggest that it is unlikely to play much of a protective role against the current dominant variants, at least through neutralizing antibody immunity. While this was not tested by Zhang et al., other work suggests that using the mRNA vaccine BNT162b2 as a booster after an initial course of CoronaVac may elicit a much better production of neutralizing antibodies against Omicron (Cheng et al., 2022).
The findings of Zhang et al. have implications for how to control SARS-CoV-2, but also Pathogen X, the hypothetical virus which will lead to the next pandemic. This work adds to existing evidence showing the strengths and weaknesses of inactivated virus vaccines such as CoronaVac, and how these can be combined with other vaccine platforms to get the best results.
References
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Milder disease with Omicron: is it the virus or the pre-existing immunity?Nature Reviews. Immunology 22:69–71.https://doi.org/10.1038/s41577-022-00678-4
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WebsiteBackground document on the inactivated vaccine Sinovac-CoronaVac against COVID-19: background document to the WHO Interim recommendations for use of the inactivated COVID-19 vaccine, CoronaVac, developed by Sinovac 24 May 2021World Health Organization. Accessed March 27, 2023.
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© 2023, Sigal
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COVID-19: Boosting in the age of Omicron
eLife 12:e87358.
https://doi.org/10.7554/eLife.87358
Further reading
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- Epidemiology and Global Health
Background:
Biological aging exhibits heterogeneity across multi-organ systems. However, it remains unclear how is lifestyle associated with overall and organ-specific aging and which factors contribute most in Southwest China.
Methods:
This study involved 8396 participants who completed two surveys from the China Multi-Ethnic Cohort (CMEC) study. The healthy lifestyle index (HLI) was developed using five lifestyle factors: smoking, alcohol, diet, exercise, and sleep. The comprehensive and organ-specific biological ages (BAs) were calculated using the Klemera–Doubal method based on longitudinal clinical laboratory measurements, and validation were conducted to select BA reflecting related diseases. Fixed effects model was used to examine the associations between HLI or its components and the acceleration of validated BAs. We further evaluated the relative contribution of lifestyle components to comprehension and organ systems BAs using quantile G-computation.
Results:
About two-thirds of participants changed HLI scores between surveys. After validation, three organ-specific BAs (the cardiopulmonary, metabolic, and liver BAs) were identified as reflective of specific diseases and included in further analyses with the comprehensive BA. The health alterations in HLI showed a protective association with the acceleration of all BAs, with a mean shift of –0.19 (95% CI −0.34, –0.03) in the comprehensive BA acceleration. Diet and smoking were the major contributors to overall negative associations of five lifestyle factors, with the comprehensive BA and metabolic BA accounting for 24% and 55% respectively.
Conclusions:
Healthy lifestyle changes were inversely related to comprehensive and organ-specific biological aging in Southwest China, with diet and smoking contributing most to comprehensive and metabolic BA separately. Our findings highlight the potential of lifestyle interventions to decelerate aging and identify intervention targets to limit organ-specific aging in less-developed regions.
Funding:
This work was primarily supported by the National Natural Science Foundation of China (Grant No. 82273740) and Sichuan Science and Technology Program (Natural Science Foundation of Sichuan Province, Grant No. 2024NSFSC0552). The CMEC study was funded by the National Key Research and Development Program of China (Grant No. 2017YFC0907305, 2017YFC0907300). The sponsors had no role in the design, analysis, interpretation, or writing of this article.
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- Epidemiology and Global Health
- Microbiology and Infectious Disease
Background:
In many settings, a large fraction of the population has both been vaccinated against and infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hence, quantifying the protection provided by post-infection vaccination has become critical for policy. We aimed to estimate the protective effect against SARS-CoV-2 reinfection of an additional vaccine dose after an initial Omicron variant infection.
Methods:
We report a retrospective, population-based cohort study performed in Shanghai, China, using electronic databases with information on SARS-CoV-2 infections and vaccination history. We compared reinfection incidence by post-infection vaccination status in individuals initially infected during the April–May 2022 Omicron variant surge in Shanghai and who had been vaccinated before that period. Cox models were fit to estimate adjusted hazard ratios (aHRs).
Results:
275,896 individuals were diagnosed with real-time polymerase chain reaction-confirmed SARS-CoV-2 infection in April–May 2022; 199,312/275,896 were included in analyses on the effect of a post-infection vaccine dose. Post-infection vaccination provided protection against reinfection (aHR 0.82; 95% confidence interval 0.79–0.85). For patients who had received one, two, or three vaccine doses before their first infection, hazard ratios for the post-infection vaccination effect were 0.84 (0.76–0.93), 0.87 (0.83–0.90), and 0.96 (0.74–1.23), respectively. Post-infection vaccination within 30 and 90 days before the second Omicron wave provided different degrees of protection (in aHR): 0.51 (0.44–0.58) and 0.67 (0.61–0.74), respectively. Moreover, for all vaccine types, but to different extents, a post-infection dose given to individuals who were fully vaccinated before first infection was protective.
Conclusions:
In previously vaccinated and infected individuals, an additional vaccine dose provided protection against Omicron variant reinfection. These observations will inform future policy decisions on COVID-19 vaccination in China and other countries.
Funding:
This study was funded the Key Discipline Program of Pudong New Area Health System (PWZxk2022-25), the Development and Application of Intelligent Epidemic Surveillance and AI Analysis System (21002411400), the Shanghai Public Health System Construction (GWVI-11.2-XD08), the Shanghai Health Commission Key Disciplines (GWVI-11.1-02), the Shanghai Health Commission Clinical Research Program (20214Y0020), the Shanghai Natural Science Foundation (22ZR1414600), and the Shanghai Young Health Talents Program (2022YQ076).
