Nanoparticle Adjuvant Design Enhances Germinal Center Responses Targeting Conserved Subdominant Epitopes for...

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Current SARS-CoV-2 vaccines target the S1 spike protein subunit, leading to limited cross-reactivity and immunity duration against variants.
• The conserved S2 subunit offers a target for broad protection, but its immunodominance in germinal center responses impedes antibody generation.

Purpose of the Study:

• To develop a nanoparticle adjuvant to enhance S2-specific B cell activation and antibody responses.
• To overcome S2 immunodominance and achieve broad, durable protection against sarbecoviruses and betacoronaviruses.

Main Methods:

• A polymeric toll-like receptor 7 agonist nanoparticle (TLR7-NP) adjuvant was designed for enhanced lymph node targeting.
• TLR7-NP was combined with Alum-adsorbed SARS-CoV-2 HexaPro spike protein.
• Humoral immune responses were compared to conventional adjuvants and mRNA vaccines.

Main Results:

• TLR7-NP promoted early germinal center recruitment of S2-specific B cells, overcoming immunodominance.
• Robust S2-specific antibody responses were induced, showing stronger humoral immunity across sarbecoviruses and betacoronaviruses.
• Long-lived plasma cell and memory B cell formation was promoted.

Conclusions:

• TLR7-NP adjuvant effectively enhances S2-specific B cell activation and antibody production.
• This approach offers a strategy for developing effective pan-coronavirus vaccines.
• The findings support direct B cell-activating adjuvant strategies for future vaccine development.