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
-
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
-
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.
Article and author information
Author details
Publication history
Copyright
© 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.
Metrics
-
- 437
- views
-
- 16
- downloads
-
- 0
- citations
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)
COVID-19: Boosting in the age of Omicron
eLife 12:e87358.
https://doi.org/10.7554/eLife.87358
Further reading
-
- Epidemiology and Global Health
- Evolutionary Biology
Several coronaviruses infect humans, with three, including the SARS-CoV2, causing diseases. While coronaviruses are especially prone to induce pandemics, we know little about their evolutionary history, host-to-host transmissions, and biogeography. One of the difficulties lies in dating the origination of the family, a particularly challenging task for RNA viruses in general. Previous cophylogenetic tests of virus-host associations, including in the Coronaviridae family, have suggested a virus-host codiversification history stretching many millions of years. Here, we establish a framework for robustly testing scenarios of ancient origination and codiversification versus recent origination and diversification by host switches. Applied to coronaviruses and their mammalian hosts, our results support a scenario of recent origination of coronaviruses in bats and diversification by host switches, with preferential host switches within mammalian orders. Hotspots of coronavirus diversity, concentrated in East Asia and Europe, are consistent with this scenario of relatively recent origination and localized host switches. Spillovers from bats to other species are rare, but have the highest probability to be towards humans than to any other mammal species, implicating humans as the evolutionary intermediate host. The high host-switching rates within orders, as well as between humans, domesticated mammals, and non-flying wild mammals, indicates the potential for rapid additional spreading of coronaviruses across the world. Our results suggest that the evolutionary history of extant mammalian coronaviruses is recent, and that cases of long-term virus–host codiversification have been largely over-estimated.
-
- Cancer Biology
- Epidemiology and Global Health
Cancer is considered a risk factor for COVID-19 mortality, yet several countries have reported that deaths with a primary code of cancer remained within historic levels during the COVID-19 pandemic. Here, we further elucidate the relationship between cancer mortality and COVID-19 on a population level in the US. We compared pandemic-related mortality patterns from underlying and multiple cause (MC) death data for six types of cancer, diabetes, and Alzheimer’s. Any pandemic-related changes in coding practices should be eliminated by study of MC data. Nationally in 2020, MC cancer mortality rose by only 3% over a pre-pandemic baseline, corresponding to ~13,600 excess deaths. Mortality elevation was measurably higher for less deadly cancers (breast, colorectal, and hematological, 2–7%) than cancers with a poor survival rate (lung and pancreatic, 0–1%). In comparison, there was substantial elevation in MC deaths from diabetes (37%) and Alzheimer’s (19%). To understand these differences, we simulated the expected excess mortality for each condition using COVID-19 attack rates, life expectancy, population size, and mean age of individuals living with each condition. We find that the observed mortality differences are primarily explained by differences in life expectancy, with the risk of death from deadly cancers outcompeting the risk of death from COVID-19.
