Memory B cell Development in Response to mRNA SARS-CoV-2 and Nanoparticle Immunization in Mice

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Nanoparticle immunogens rapidly induce high antibody levels and are used in new vaccines.
• The capacity of nanoparticle vaccines to generate durable memory B cell responses is not fully understood.

Purpose of the Study:

• Compare serologic and memory B cell responses to SARS-CoV-2 mRNA, homotypic beta nanoparticle, and mosaic 8b nanoparticle vaccines.
• Evaluate the breadth and characteristics of immune responses elicited by different vaccine platforms.

Main Methods:

• Prime boost vaccination in mice using SARS-CoV-2 Wuhan-Hu-1 mRNA vaccine, SARS-CoV-2 B.1.351 homotypic nanoparticle, or mosaic 8b nanoparticle.
• Analysis of serologic antibody levels, neutralizing titers, and memory B cell responses.
• Derivation and characterization of monoclonal antibodies from memory B cells.

Main Results:

• Memory B cells from all three vaccine regimens had similar antibody sequences, somatic mutation levels, and clonal diversity.
• Mosaic nanoparticles elicited broader serologic responses against some mismatched strains than the mRNA vaccine.
• mRNA vaccination resulted in the highest serum neutralizing titers against SARS-CoV-2.
• Monoclonal antibodies from mosaic 8b nanoparticle-vaccinated mice showed greater breadth against SARS-CoV-2 variants.

Conclusions:

• Both mRNA and nanoparticle vaccines elicit memory B cells producing antibodies against diverse RBD epitopes.
• Mosaic 8b nanoparticle immunogens enhance the breadth of memory B cell-derived antibodies against SARS-CoV-2 variants.
• mRNA and nanoparticle vaccines possess distinct strengths in eliciting immune responses.