Biology subjects

Bowen, A. D.

Publications and source records attributed to Bowen, A. D..

3 recordsLinked to original sources

bioRxiv2023

SARS-CoV-2 Neutralizing Antibodies After Bivalent vs. Monovalent Booster

Bivalent mRNA vaccine boosters expressing Omicron BA.5 spike and ancestral D614G spike were introduced to attempt to boost waning antibody titers and broaden coverage against emerging SARS-CoV-2 lineages. Previous reports showed that peak serum neutralizing antibody (NAb) titers against SARS-CoV-2 variants following bivalent booster were similar to peak titers following monovalent booster. It remains unknown whether these antibody responses would diverge over time. We assessed serum virus-neutralizing titers in 41 participants who received three monovalent mRNA vaccine doses followed by bivalent booster, monovalent booster, or BA.5 breakthrough infection at one month and three months after the last vaccine dose or breakthrough infection using pseudovirus neutralization assays against D614G and Omicron subvariants (BA.2, BA.5, BQ.1.1, and XBB.1.5). There was no significant difference at one month and three months post-booster for the two booster cohorts. BA.5 breakthrough patients exhibited significantly higher NAb titers at three months against all Omicron subvariants tested compared against monovalent and bivalent booster cohorts. There was a 2-fold drop in mean NAb titers in the booster cohorts between one and three month time points, but no discernible waning of titers in the BA.5 breakthrough cohort over the same period. Our results suggest that NAb titers after boosting with one dose of bivalent mRNA vaccine are not higher than boosting with monovalent vaccine. Perhaps inclusion of D614G spike in the bivalent booster exacerbates the challenge posed by immunological imprinting. Hope remains that a second bivalent booster could induce superior NAb responses against emerging variants.

microbiology↗

bioRxiv2022

Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants

The SARS-CoV-2 Omicron variant continues to evolve, with new BQ and XBB subvariants now rapidly expanding in Europe/US and Asia, respectively. As these new subvariants have additional spike mutations, they may possess altered antibody evasion properties. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals who were boosted with a WA1/BA.5 bivalent mRNA vaccine. Compared to the ancestral strain D614G, serum neutralizing titers against BQ and XBB subvariants were lower by 13-81-fold and 66-155-fold, respectively, far beyond what had been observed to date. A panel of monoclonal antibodies capable of neutralizing the original Omicron variant, including those with Emergency Use Authorization, were largely inactive against these new subvariants. The spike mutations that conferred antibody resistance were individually studied and structurally explained. Finally, the ACE2-binding affinities of the spike proteins of these novel subvariants were found to be similar to those of their predecessors. Taken together, our findings indicate that BQ and XBB subvariants present serious threats to the efficacy of current COVID-19 vaccines, render inactive all authorized monoclonal antibodies, and may have gained dominance in the population because of their advantage in evading antibodies.

microbiology↗

bioRxiv2022

SARS-CoV-2 Omicron BA.2.12.1, BA.4, and BA.5 subvariants evolved to extend antibody evasion

SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged dramatically to become dominant in the United States and South Africa, respectively1,2. These novel subvariants carrying additional mutations in their spike proteins raise concerns that they may further evade neutralizing antibodies, thereby further compromising the efficacy of COVID-19 vaccines and therapeutic monoclonals. We now report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. However, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections. Mutation at spike residue L452 found in both BA.2.12.1 and BA.4/5 facilitates escape from some antibodies directed to the so-called class 2 and 3 regions of the receptor-binding domain3. The F486V mutation found in BA.4/5 facilitates escape from certain class 1 and 2 antibodies but compromises the spike affinity for the viral receptor. The R493Q reversion mutation, however, restores receptor affinity and consequently the fitness of BA.4/5. Among therapeutic antibodies authorized for clinical use, only bebtelovimab retains full potency against both BA.2.12.1 and BA.4/5. The Omicron lineage of SARS-CoV-2 continues to evolve, successively yielding subvariants that are not only more transmissible but also more evasive to antibodies.

microbiology↗