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.
  1. Alex Sigal  Is a corresponding author
  1. 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.


Article and author information

Author details

  1. Alex Sigal

    Alex Sigal is at the Africa Health Research Institute, Durban, South Africa

    For correspondence
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8571-2004

Publication history

  1. Version of Record published: April 17, 2023 (version 1)


© 2023, Sigal

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.


  • 430
  • 16
  • 0

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

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Alex Sigal
COVID-19: Boosting in the age of Omicron
eLife 12:e87358.

Further reading

    1. Epidemiology and Global Health
    Xiaoxin Yu, Roger S Zoh ... David B Allison
    Review Article

    We discuss 12 misperceptions, misstatements, or mistakes concerning the use of covariates in observational or nonrandomized research. Additionally, we offer advice to help investigators, editors, reviewers, and readers make more informed decisions about conducting and interpreting research where the influence of covariates may be at issue. We primarily address misperceptions in the context of statistical management of the covariates through various forms of modeling, although we also emphasize design and model or variable selection. Other approaches to addressing the effects of covariates, including matching, have logical extensions from what we discuss here but are not dwelled upon heavily. The misperceptions, misstatements, or mistakes we discuss include accurate representation of covariates, effects of measurement error, overreliance on covariate categorization, underestimation of power loss when controlling for covariates, misinterpretation of significance in statistical models, and misconceptions about confounding variables, selecting on a collider, and p value interpretations in covariate-inclusive analyses. This condensed overview serves to correct common errors and improve research quality in general and in nutrition research specifically.

    1. Ecology
    2. Epidemiology and Global Health
    Emilia Johnson, Reuben Sunil Kumar Sharma ... Kimberly Fornace
    Research Article

    Zoonotic disease dynamics in wildlife hosts are rarely quantified at macroecological scales due to the lack of systematic surveys. Non-human primates (NHPs) host Plasmodium knowlesi, a zoonotic malaria of public health concern and the main barrier to malaria elimination in Southeast Asia. Understanding of regional P. knowlesi infection dynamics in wildlife is limited. Here, we systematically assemble reports of NHP P. knowlesi and investigate geographic determinants of prevalence in reservoir species. Meta-analysis of 6322 NHPs from 148 sites reveals that prevalence is heterogeneous across Southeast Asia, with low overall prevalence and high estimates for Malaysian Borneo. We find that regions exhibiting higher prevalence in NHPs overlap with human infection hotspots. In wildlife and humans, parasite transmission is linked to land conversion and fragmentation. By assembling remote sensing data and fitting statistical models to prevalence at multiple spatial scales, we identify novel relationships between P. knowlesi in NHPs and forest fragmentation. This suggests that higher prevalence may be contingent on habitat complexity, which would begin to explain observed geographic variation in parasite burden. These findings address critical gaps in understanding regional P. knowlesi epidemiology and indicate that prevalence in simian reservoirs may be a key spatial driver of human spillover risk.