# Memory B cell development in response to mRNA SARS-CoV-2 and nanoparticle immunization in mice

## TL;DR

This study compares how mRNA and nanoparticle vaccines affect memory B cell development in mice, showing each vaccine's unique strengths in antibody breadth and neutralizing power.

## Contribution

The study reveals that mosaic 8b nanoparticle vaccines enhance memory B cell-derived antibody breadth compared to mRNA vaccines.

## Key findings

- mRNA vaccines produce higher serum neutralizing titers against SARS-CoV-2.
- Mosaic 8b nanoparticle vaccines elicit monoclonal antibodies with broader neutralizing activity against variants.
- All vaccines generate memory B cells with similar mutation levels and epitope targeting diversity.

## Abstract

Nanoparticle vaccines are promising next-generation vaccine candidates, yet their capacity to generate durable memory B cell responses remains incompletely understood. We compared immune responses following SARS-CoV-2 mRNA, homotypic beta nanoparticle, or mosaic 8b nanoparticle vaccination in mice. Serum antibody neutralizing responses against a panel of SARS-CoV-2 variants elicited by an mRNA vaccine were equivalent or superior to those elicited by mosaic 8b nanoparticle vaccines. However, the monoclonal antibodies derived from memory B cells elicited by the mosaic 8b nanoparticle showed better neutralizing breadth against heterologous pseudoviruses. These findings highlight individual strengths of mRNA and nanoparticle vaccines and show that mosaic 8b nanoparticle immunogens can enhance the breadth of memory B cell–derived antibodies.

Nanoparticle immunogens excel at rapidly inducing high levels of circulating antibodies and are being deployed as part of several novel vaccines. However, their ability to elicit memory B cell responses is less well understood. Here, we compared serologic and memory B cell responses after prime boost vaccination with either SARS-CoV-2 Wuhan-Hu-1 mRNA vaccine, or protein nanoparticles: SARS-CoV-2 B.1.351 homotypic containing a single receptor binding domain (RBD); (homotypic beta) or a combination of different Sarbecovirus RBDs (mosaic 8b), respectively. The memory B cells elicited by the 3 vaccine regimens showed closely related antibody sequences, similar levels of somatic mutation, and clonal diversity. The breadth of serologic responses elicited by the mosaic nanoparticles was comparable to the homotypic nanoparticle and superior to the mRNA vaccine for some mismatched strains. However, serum neutralizing titers to SARS-CoV-2 were highest after mRNA vaccination. The three vaccines elicited memory B cells that produced antibodies specific to a broad range of epitopes on the RBD that differed in a way that may reflect epitope masking. Monoclonal antibodies derived from memory B cells elicited by the mosaic 8b nanoparticle showed greater breadth against a panel of SARS-CoV-2 variants and SARS-CoV.