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 antibodies, but their memory B cell response is unclear.
• Understanding memory B cell responses is crucial for novel vaccine development.

Purpose of the Study:

• Compare serologic and memory B cell responses to SARS-CoV-2 mRNA vaccine versus nanoparticle vaccines.
• Evaluate antibody sequence, somatic mutation, clonal diversity, and breadth of response.
• Assess neutralizing titers and epitope specificity.

Main Methods:

• Prime boost vaccination with SARS-CoV-2 mRNA vaccine, homotypic beta nanoparticle, or mosaic 8b nanoparticle.
• Analysis of memory B cell antibody sequences, somatic mutation, and clonal diversity.
• Measurement of serologic breadth, neutralizing titers, and epitope specificity.

Main Results:

• Memory B cells from all three regimens showed similar antibody sequences, somatic mutation, and diversity.
• Mosaic nanoparticles provided broader serologic responses than mRNA vaccine for some strains.
• mRNA vaccination yielded the highest SARS-CoV-2 neutralizing titers.
• Memory B cells produced antibodies targeting diverse RBD epitopes, suggesting epitope masking.
• Mosaic 8b nanoparticle-derived antibodies showed broader reactivity against SARS-CoV-2 variants.

Conclusions:

• Nanoparticle and mRNA vaccines induce distinct but related memory B cell populations.
• Mosaic nanoparticles offer broader humoral immunity against SARS-CoV-2 variants.
• Further research is needed to optimize nanoparticle vaccine design for robust memory B cell induction.