Two Vaccines for Staphylococcus aureus Induce a B-Cell-Mediated Immune Response

Area of Science:

• Immunology
• Vaccinology
• Microbiology

Background:

• *Staphylococcus aureus* poses a significant threat due to the absence of a licensed human vaccine.
• *S. aureus* vaccines require a multi-component approach, as single-antigen vaccines have proven ineffective.
• The impact of combining protein antigens with capsular polysaccharides (CPs) in *S. aureus* vaccines on immune responses is not well understood.

Purpose of the Study:

• To compare the immune responses induced by a bivalent CP conjugate vaccine versus a novel multi-component *S. aureus* vaccine (SA4Ag) in cynomolgus macaques.
• To investigate the effects of protein antigens on CP-specific antibody and T-cell responses.
• To assess the functional antibody and innate immune responses elicited by both vaccine candidates.

Main Methods:

• Cynomolgus macaques were vaccinated with either a bivalent CP conjugate vaccine or the SA4Ag vaccine.
• Immune responses were analyzed using microengraving, flow cytometry, opsonophagocytic assays, and Luminex technology.
• Key readouts included B-cell activation, T-cell cytokine production, functional antibody levels, and innate immune cell activity.

Main Results:

• Both vaccines induced cytokine production from naive cells, memory B-cell responses, and functional antibody titers.
• No significant increases in circulating activated T cells or T_H17/T_H1 responses were observed post-vaccination.
• Data suggest vaccine-induced recruitment of T follicular helper (T_FH) cells to lymph nodes.

Conclusions:

• The addition of protein antigens to CP conjugates in the SA4Ag vaccine did not substantially alter B-cell mobilization or functional antibody responses.
• The immune response to SA4Ag appears to be primarily mediated by B cells and antibodies targeting *S. aureus* virulence factors.
• Protection against *S. aureus* mediated by SA4Ag may rely predominantly on antibody efficacy.