On the 21st of November, 2021, the World Health Organization (WHO) reported the emergence of a new variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Botswana. This variant is now known as the Omicron variant (BA.1/B.1.1.529) and has been categorized as a variant of concern (VOC), as it possesses novel mutations with the potential for immune evasion.
Study: mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant. Image Credit: peterschreiber.media/Shutterstock
Background
This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources
Scientists have reported that the Omicron variant consists of fifty-nine mutations throughout the genome, including thirty-six spike protein mutations. The main function of the spike protein of the SARS-CoV-2 is to bind with the angiotensin-converting enzyme 2 (ACE2) of the host and promote virus invasion into the host cell. To date, all available coronavirus disease 2019 (COVID-19) vaccines and therapeutics have been designed against the spike protein of this virus.
Previous studies have revealed that mutations in the receptor-binding domain (RBD) of the spike protein cause evasion from vaccine-induced neutralizing antibodies and increase the rate of transmission compared to the original SARS-CoV-2 strain. Researchers revealed that the Omicron variant harbors fifteen mutations in the RBD region and some of the mutations overlap with previous variants such as Beta and Gamma. These mutations are K417, E484, and N501, which are responsible for decreasing vaccine-induced neutralization of antibodies.
Three vaccines have received emergency use authorization (EUA) from the US Food and Drug Administration (FDA). All of them have been designed against the spike protein of the original SARS-CoV-2 strain reported in 2019 in Wuhan, China. Two vaccines are based on mRNA in lipid nanoparticles, and the third is based on an adenovirus vector.
The mRNA-based vaccines have been developed by Pfizer-BioNTech (BNT162b2) and Moderna (mRNA1273), whereas the adenovirus vectored COVID-19 vaccine (Ad26.COV2.S) has been developed by Janssen/Johnson & Johnson. These vaccines have successfully induced humoral and cellular immune responses in the recipient and reduced the mortality and hospitalization rate significantly. However, the protective power of these vaccines is reduced with increased time post-vaccination. The VOCs have also brought about a decline in vaccine efficacy.
To tackle the problems of decreasing antibody responses over time and the emergence of new SARS-CoV-2 variants, researchers and healthcare officials have developed a booster vaccination strategy for individuals who were vaccinated six months ago. Some of the latest reports have shown that this strategy is extremely effective as it can induce a high level of neutralizing antibody titers. However, it is unclear if the booster vaccination strategy will remain effective against the Omicron variant.
A new study
Researchers have previously designed and validated a high-throughput pseudovirus neutralization assay to evaluate differences in immune response elicited by vaccines and access host characteristics against SARS-CoV-2 variants and other coronaviruses.
A new study, published on the medRxiv* preprint server, has used this assay to evaluate sera, obtained from 239 individuals vaccinated via any of the above-stated vaccines against SARS-CoV-2’s original strain, the Delta, and Omicron SARS-CoV-2 pseudoviruses. The study cohort included seventy participants vaccinated with an mRNA vaccine booster, i.e., six months after primary vaccination, as a cross-over or mRNA-based vaccination regimen.
The authors found that all three types of primary vaccination resulted in minimal to negative neutralization of the Omicron variant. However, importantly, mRNA booster vaccination individuals have shown significant neutralization against Omicron. Although, the neutralization titers of individuals who received boosted mRNA were similar to those who were vaccinated recently, i.e., completed a two-dose COVID-19 vaccine regime. This is interesting because the antigen used in developing the booster vaccine is identical to the one used in the primary series.
Scientists suggest that neutralization titers produced after COVID-19 booster vaccination resulted in cross-reactive humoral immunity with greater breadth than equivalent neutralization titers achieved with primary vaccination alone. Researchers believe primary vaccination failed to fully stimulate B cell responses against each of the possible epitopes on the spike antigen.
Based on the in-vitro infectivity experiments, this study reported that Omicron pseudovirus, similar to the original SARS-CoV-2 strain, depends upon the human ACE2 receptor for penetrating the host cell. Scientists reported that the Omicron variant has a high transmission rate, i.e., it is almost four times more infectious than the wild-type pseudovirus and twice that of Delta pseudovirus.
This study revealed that the Omicron variant escapes vaccine-induced neutralizing immune response under current two-dose COVID-19 vaccination regimens. Nonetheless, one of the most important findings of this study has been revealing the effectiveness of cross-neutralizing immunity against Omicron in boosted individuals.
Conclusion
This study has some limitations, including using pseudovirus neutralization assay. Although this assay has shown excellent results against previous coronavirus strains, there is a possibility that the mutations in Omicron spike protein may cause Omicron pseudovirus to behave differently.
Another limitation is that the study cohort was cross-sectional and not longitudinal. Therefore, the authors could not measure changes in the neutralization titers over time across single individuals. This study has revealed the effectiveness of the COVID-19 booster and supports the need for rapid and coordinated deployment of mRNA booster vaccination to contain the ongoing COVID-19 pandemic.
This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources
Article Revisions
- May 9 2023 - The preprint preliminary research paper that this article was based upon was accepted for publication in a peer-reviewed Scientific Journal. This article was edited accordingly to include a link to the final peer-reviewed paper, now shown in the sources section.
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