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Increased memory B cell potency and breadth after a SARS-CoV-2 mRNA boost.

ABSTRACT: The Omicron variant of SARS-CoV-2 infected many vaccinated and convalescent individuals^1-3. Despite the reduced protection from infection, individuals who received three doses of an mRNA vaccine were highly protected from more serious consequences of infection⁴. Here we examine the memory B cell repertoire in a longitudinal cohort of individuals receiving three mRNA vaccine doses^5,6. We find that the third dose is accompanied by an increase in, and evolution of, receptor-binding domain (RBD)-specific memory B cells. The increase is due to expansion of memory B cell clones that were present after the second dose as well as the emergence of new clones. The antibodies encoded by these cells showed significantly increased potency and breadth when compared with antibodies obtained after the second dose. Notably, the increase in potency was especially evident among newly developing clones of memory cells, which differed from persisting clones in targeting more conserved regions of the RBD. Overall, more than 50% of the analysed neutralizing antibodies in the memory compartment after the third mRNA vaccine dose neutralized the Omicron variant. Thus, individuals receiving three doses of an mRNA vaccine have a diverse memory B cell repertoire that can respond rapidly and produce antibodies capable of clearing even diversified variants such as Omicron. These data help to explain why a third dose of a vaccine that was not specifically designed to protect against variants is effective against variant-induced serious disease.

SUBMITTER: Muecksch F

PROVIDER: S-EPMC9259484 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Increased memory B cell potency and breadth after a SARS-CoV-2 mRNA boost.

Muecksch Frauke F Wang Zijun Z Cho Alice A Gaebler Christian C Ben Tanfous Tarek T DaSilva Justin J Bednarski Eva E Ramos Victor V Zong Shuai S Johnson Brianna B Raspe Raphael R Schaefer-Babajew Dennis D Shimeliovich Irina I Daga Mridushi M Yao Kai-Hui KH Schmidt Fabian F Millard Katrina G KG Turroja Martina M Jankovic Mila M Oliveira Thiago Y TY Gazumyan Anna A Caskey Marina M Hatziioannou Theodora T Bieniasz Paul D PD Nussenzweig Michel C MC

Nature 20220421 7917

The Omicron variant of SARS-CoV-2 infected many vaccinated and convalescent individuals1-3. Despite the reduced protection from infection, individuals who received three doses of an mRNA vaccine were highly protected from more serious consequences of infection4. Here we examine the memory B cell repertoire in a longitudinal cohort of individuals receiving three mRNA vaccine doses5,6. We find that the third dose is accompanied by an increase in, and evolution of, ...[more]

PMID: 35447027

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Project description:BackgroundEmerging evidence suggests heterologous prime-boost COVID-19 vaccination as a superior strategy than homologous schedules. Animal experiments and clinical observations have shown enhanced antibody response against influenza variants after heterologous vaccination; however, whether the inoculation order of COVID-19 vaccines in a prime-boost schedule affects antibody response against SARS-CoV-2 variants is not clear.MethodsWe conducted immunological analyses in a cohort of health care workers (n = 486) recently vaccinated by three types of inactivated COVID-19 vaccines under homologous or heterologous prime-boost schedules. Antibody response against ancestral SARS-CoV-2 (Wuhan-Hu-1) was assessed by total antibody measurements, surrogate virus neutralization tests, and pseudovirus neutralization assays (PNA). Furthermore, serum neutralization activity against SARS-CoV-2 variants of concern was also measured by PNA.FindingsWe observed strongest serum neutralization activity against the widely circulating SARS-CoV-2 variant B.1.617.2 among recipients of heterologous BBIBP-CorV/CoronaVac and WIBP-CorV/CoronaVac. In contrast, recipients of CoronaVac/BBIBP-CorV and CoronaVac/WIBP-CorV showed significantly lower B.1.617.2 neutralization titers than recipients of reverse schedules. Laboratory tests revealed that neutralizing activity against common variants but not the ancestral SARS-CoV-2 was associated with the inoculation order of heterologous prime-boost vaccines. Multivariable regression analyses confirmed this association after adjusting for known confounders.ConclusionsOur data provide clinical evidence of inoculation order-dependent expansion of neutralizing breadth against SARS-CoV-2 in recipients of heterologous prime-boost vaccination and call for further studies into its underlying mechanism.FundingNational Key R&D Program of China, National Development and Re-form Commission of China, National Natural Science Foundation of China, Shenzhen Science and Technology Innovation Commission, and US Department of Veterans Affairs.

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Increased memory B cell potency and breadth after a SARS-CoV-2 mRNA boost.

Publications

Increased memory B cell potency and breadth after a SARS-CoV-2 mRNA boost.

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