Immunogenicity of a third dose with mRNA-vaccines in the ChAdOx1-S/BNT162b2 vaccination regimen against SARS-CoV-2 variants

TL;DR

A third dose of mRNA-1273 vaccine after ChAdOx1-S/BNT162b2 primes boosts antibody levels against SARS-CoV-2 variants more than a third BNT162b2 dose.

Contribution

Shows mRNA-1273 outperforms BNT162b2 as a third dose in neutralizing SARS-CoV-2 variants.

Findings

mRNA-1273 third dose induced higher neutralizing antibodies against Delta and BA.1 Omicron at day 28.

mRNA-1273 third dose showed higher neutralizing titers against G614 variant at day 90.

Suboptimal neutralization against BQ.1.1, XBB.1.5/XBB.1.9, and JN.1 variants was observed at day 180.

Abstract

CombiVacS study has demonstrated a strong immune response of the heterologous ChAdOx1-S/BNT162b2 vaccine combination. The primary outcomes of the study were to assess the humoral immune response against SARS-CoV-2, 28 days after a third dose of a mRNA vaccine, in subjects that received a previous prime-boost scheme with ChAdOx1-S/BNT162b2. Secondary outcomes extended the study to 3 and 6 months. The third vaccine dose of mRNA-1273 in naive participants previously vaccinated with ChAdOx1-S/BNT162b2 regimen reached higher neutralizing antibodies titers against the variants of concern Delta and BA.1 lineage of Omicron compared with those receiving a third dose of BNT162b2 at day 28. These differences between BNT162b2 and mRNA-1273 arms were observed against the ancestral variant G614 at day 90. Suboptimal neutralizing response was observed against BQ.1.1, XBB.1.5/XBB.1.9, and JN.1 in a relevant proportion of individuals 180 days after the third dose, even after asymptomatic Omicron breakthrough infections. EudraCT (2021-001978-37); ClinicalTrials.gov (NCT04860739).

•Higher NT50 titers was observed in mRNA-1273 arm against Delta and BA.1 at day 28•Higher NT50 titers was observed in mRNA-1273 arm against G614 variant at day 90•Suboptimal neutralization against recent Omicron variants was observed at day 180•Asymptomatic breakthrough infections do not ensure XBB.1.5 and JN.1 neutralization

Higher NT50 titers was observed in mRNA-1273 arm against Delta and BA.1 at day 28

Higher NT50 titers was observed in mRNA-1273 arm against G614 variant at day 90

Suboptimal neutralization against recent Omicron variants was observed at day 180

Asymptomatic breakthrough infections do not ensure XBB.1.5 and JN.1 neutralization

Immunology; Immune response

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