mRNA-based influenza vaccine expands the B cell response breadth in humans

Area of Science:

• Immunology
• Vaccinology
• Molecular Biology

Background:

• Conventional influenza vaccines offer limited antibody breadth.
• The capacity of mRNA influenza vaccines to induce robust germinal center (GC) responses in humans is not well understood.

Purpose of the Study:

• To compare B cell responses, including GC reactions, between mRNA and conventional influenza vaccines.
• To investigate the impact of mRNA vaccination on antibody repertoire diversity and breadth.

Main Methods:

• Observational study in healthy adults receiving mRNA or split-virion quadrivalent influenza vaccines over two seasons.
• Analysis of B cell responses, antibody titers, memory B cell frequencies, and GC reactions in lymph nodes.
• Proteomic and lineage analyses of serum IgG repertoire.

Main Results:

• mRNA vaccines induced higher antibody titers and memory B cell frequencies.
• Sustained GC reactions were observed in lymph nodes for at least 26 weeks post-mRNA vaccination.
• mRNA vaccination expanded vaccine-elicited IgG clonotypes, enhanced intraclonal expansion, and increased binding breadth against divergent influenza viruses.

Conclusions:

• Persistent GC responses are crucial for broadening vaccine-induced antibody repertoires.
• mRNA influenza vaccines promote GC-driven antibody evolution, leading to enhanced breadth and potentially improved protection.