In a recent study posted to the medRxiv* preprint server, researchers summarized existing data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant’s sub-variant (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.3, and BA.4/5) neutralization. They also performed a comparative assessment of cross-neutralizing responses of Omicron subvariants in comparison to the Wuhan-Hu-1 strain (prototype) antigen.
Study: Post-vaccination neutralization responses to Omicron sub-variants. Image Credit: Naeblys/Shutterstock
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
The continual evolution of Omicron and the consequent emergence of subvariants with higher transmissibility and immune-evasiveness has threatened vaccination efficacy with reductions in vaccination-induced cross-neutralization responses. In vitro studies have reported markedly lower Ab (antibody) function against the Omicron spike (S) protein among convalescent and vaccinated individuals with a prior history of non-Omicron infections.
About the study
In the present study, researchers assessed Omicron subvariant neutralization responses induced by coronavirus disease 2019 (COVID-19) vaccinations.
Databases such as PubMed, medRxiv and bioRxiv were searched between 26 November 2021 and 25 July 2022, for studies evaluating post-COVID-19 vaccination neutralizing Ab (nAb) responses to Omicron subvariants. The study was ancillary to a literature review. It included only published studies or preprints assessing nAb responses for ≥1 Omicron subvariant induced by a World Health Organization (WHO)-approved COVID-19 vaccine. It also analyzed samples obtained in <6 months of the most recent vaccination.
Data were obtained on the neutralization assay, reference SARS-CoV-2 strain, sample size, vaccination doses, vaccination type, duration between the most recent vaccination and sample collection, nAb titers for Wuhan-Hu-1 strain, and Omicron subvariants and sample proportions with detectable nAb titers or the prototype strain and each sub-variant.
Studies were excluded if surrogate neutralization assays were used, immunosuppressed individuals were sampled, and the study cohorts comprised preselected low- or high-responders. Studies with >20% of individuals with hybrid (natural infection and vaccination) immunity were also excluded. Median fold-reductions in Omicron subvariant nAb titers in comparison to each other and the Wuhan-Hu-1 strain were assessed, and the median strain-wise responder percentages were calculated.
Results
In total, abstracts of 6,318 studies were screened, of which, only 213 studies were eligible for full-text review, 153 of which were considered for the final analysis. About 80% (n=122 studies) studies evaluated fold reductions of Omicron subvariants in relation to the Wuhan-Hu-1 strain, 22% (n=33) studies evaluated fold reductions of other Omicron subvariants concerning Omicron BA.1, and 88% (n=135) provided data on the percentage of responses to ≥1 Omicron subvariant.
Among included studies, post-primary COVID-19 vaccination, subvariant-wise fold-reductions in nAb titers concerning the Wuhan-Hu-1 strain showed wide variations, from 4.2-fold reductions for Omicron BA.3 to 22-fold for Omicron BA.4/5. Among boosted individuals, fold-reductions were comparable for all Omicron subvariants (between six-fold and seven-fold), with an exception for Omicron BA.4/5 subvariant (13-fold).
The nAb titers induced after primary vaccinations and booster vaccinations were similar for all Omicron subvariants, except BA.4/5 for which fold-reductions were higher (two-fold higher) in relation to Omicron BA.1. Omicron subvariant-wise percentages of responders were low after primary COVID-19 vaccination (between 34% and 57%) in comparison to the Wuhan-Hu-1 strain (96%). Still, they increased after booster vaccinations (between 85% and 93%).
Of the studies included, 82% (n=125 studies) provided data on fold-reductions of ≥1 Omicron subvariant in relation to the Wuhan-Hu-1 strain. Post-primary COVID-19 vaccinations, fold-reductions in relation to the Wuhan-Hu-1 strain were large for all the Omicron subvariants, ranging between 4.2-fold for Omicron BA.3 and 22-fold for Omicron BA.4/BA.5 subvariants and were observed across all vaccine platforms, with greatest reductions (42.5-fold) by protein subunit-based COVID-19 vaccines.
Fold-reductions against Omicron BA.1 in relation to the Wuhan-Hu-1 strain were higher (21-fold) for messenger ribonucleic acid (mRNA) COVID-19 vaccines in comparison to vector-based vaccines (12-fold) and inactivated COVID-19 vaccines (11-fold). Further, fold-reductions for heterologous COVID-19 vaccination strategies involving mRNA vaccines were large (22-fold).
Post booster vaccinations, nAb titer fold-reductions for Omicron subvariants in relation to the Wuhan-Hu-1 prototype were not as prominent as those observed post-primary vaccinations and ranged between six-fold for Omicron BA.2 and 13-fold for Omicron BA.4/5. Median nAb fold-reductions were eight-fold, nine-fold, 10-fold, and six-fold greater for Omicron BA.1 by vector-based, inactivated, and protein-based vaccines compared to those for mRNA vaccines; however, the results were heterogeneous.
Overall, the study findings showed that nAb titer fold-reductions of Omicron subvariants in relation to the Wuhan-Hu-1 strain varied considerably after primary COVID-19 vaccinations but were similar after booster vaccinations, except for Omicron BA.4/5, for which fold-reductions were higher. The findings showed that vaccine efficacy is likely lower for Omicron subvariants, especially for BA.4/5.
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 15 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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