Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination provides efficient protection against symptomatic and severe COVID-19. However, the emergence of novel variants like the SARS-CoV-2 Omicron variant and its subvariants has adversely impacted the effectiveness of the currently used vaccination regimes, which were derived from the SARS-CoV-2 ancestral variant.
About the study
In the present study, researchers performed a meta-analysis using currently available data on neutralization titers obtained from clinical studies that compared the booster COVID-19 vaccination with the currently available SARS-CoV-2 ancestral strain- or variant-based vaccines.
The team compared the average extent of boosting between vaccines based on the ancestral strain and those modified as per the variant by comparing the increase in neutralization titers noted before and after booster dose administration. Furthermore, the study compared the magnitude of boosting against the homologous strains, wherein the variants used in the vaccine and the neutralization assay are the same, versus non-homologous strains, wherein the variants used in the vaccine and the neutralization assay are different.
The clinical benefits associated with replacing ancestral-based boosters with variant-modified booster vaccines were assessed using a model that correlated neutralization titers and the clinical protection observed. The model was used to predict the benefits of booster vaccine administration with an ancestral-based vaccine compared to those with a variant-modified vaccine. The team evaluated the relative effect of an ancestral-based booster vaccine that resulted in an 11-fold increase in neutralizing antibody titers compared to a variant-modified booster that led to a further 1.5-fold higher antibody titer than the ancestral booster. The average protection elicited by different booster vaccines was estimated over six months, assuming a similar rate of antibody titer decay for both vaccines.
The study results showed that the SARS-CoV-2 ancestral-based vaccines improved neutralization titers by an average of 11 times compared to pre-booster titers. While the variant-modified vaccines did not display any increase in neutralization against the ancestral strain compared to the ancestral-based vaccines, the variant-modified vaccines showed more potent neutralization of the variants analyzed. The team also found that the variant-modified vaccines led to an average of 1.51 times increase in titers compared to the ancestral-based vaccines.
Furthermore, the level of boosting observed was considerably higher for the homologous strains. However, no significant difference was found between the impact of monovalent and bivalent vaccines. Interestingly, the team noted that for a population that was either previously vaccinated or infected with SARS-CoV-2 and had 50% protection against contracting a symptomatic infection, an ancestral-based booster vaccine that resulted in an 11-fold increase in neutralizing antibody titers could lead to an increase from 50% to 86% in average protection against symptomatic infection over six months.
On the other hand, a variant-modified booster vaccine that showed a 1.5-fold increase in neutralizing antibody titers could lead to average protection of 90.2%.
The present study demonstrated a method that predicted the relative effectiveness associated with different formulations of COVID-19 booster vaccines, taking into account the comparative increase in neutralization titers and the variation in antibody titers against different SARS-CoV-2 variants. The study findings indicated that variant-modified booster vaccines could result in significantly higher neutralization titers against prevalent and ancestral SARS-CoV-2 variants compared to ancestral-based boosters.
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