Phosphate substitution in an AlOOH - TLR4 adjuvant system (SPA08) modulates the immunogenicity of Serovar E MOMP from...

Area of Science:

• Vaccinology
• Immunology
• Microbiology

Background:

• Chlamydia trachomatis is a common sexually transmitted pathogen necessitating an effective vaccine.
• The Major Outer Membrane Protein (MOMP) is a key immunogenic target for Chlamydia trachomatis vaccines.

Purpose of the Study:

• To investigate the impact of phosphate substitution in an aluminum oxyhydroxide (AlOOH)-based adjuvant (SPA08) on the properties and immunogenicity of a recombinant MOMP (rMOMP) vaccine.
• To evaluate how varying phosphate levels in the adjuvant affect antigen adsorption and subsequent immune responses.

Main Methods:

• Formulation of an experimental vaccine using serovar E rMOMP and the SPA08 adjuvant system with varying phosphate substitutions.
• Assessment of physicochemical properties including adsorptive capacity and coefficient for rMOMP and the TLR4 agonist E6020.
• Immunogenicity studies in CD1 mice measuring serum IgG titers (total, IgG1, IgG2a), in vitro neutralization, and cytokine secretion from splenocytes.

Main Results:

• Increased phosphate substitution in AlOOH significantly decreased adsorptive capacity for both rMOMP and E6020.
• Phosphate substitution reduced rMOMP adsorption but not E6020 adsorption in vaccine formulations.
• Higher phosphate substitution correlated with increased rMOMP-specific IgG and IgG1 titers, enhanced in vitro neutralization, and reduced pro-inflammatory cytokine release.

Conclusions:

• The degree of phosphate substitution in AlOOH-based adjuvants critically influences the adsorption of antigens and agonists.
• Phosphate substitution in the SPA08 adjuvant modulates both humoral and cellular immune responses to the rMOMP vaccine.
• Optimizing phosphate levels in AlOOH adjuvants holds potential for enhancing the efficacy of Chlamydia trachomatis vaccines.