A gamma-irradiated pneumococcal vaccine elicits superior immunogenicity in comparison to heat or chemically inactivated whole-cell vaccines

Streptococcus pneumoniae is one of the world's foremost bacterial pathogens, with extensive serotype diversity that impacted the efficacy of current vaccines. Our group have previously reported the generation of a whole cell serotype-independent gamma-irradiated pneumococcal vaccine (Gamma-PN). The present study sought to compare the effect of gamma-irradiation, heat, ethanol, or formalin inactivation on the antigenic structure and immunogenicity of whole-cell pneumococcal vaccines. Our data demonstrate that Gamma-PN exhibited comparable cellular morphology to live bacteria, in contrast to damage and aggregation observed for other approaches. Vaccination of mice with Gamma-PN or heat-inactivated PN (Heat-PN) induced high levels of pneumococcal-specific IgG, but with significantly different profiles of IgG subclasses. In addition, while immune sera from Heat-PN vaccinated mice had strong PspA-specific responses, sera from Gamma-PN vaccinated animals showed enhanced recognition of a wider array of pneumococcal proteins. Overall, in contrast to other methods of inactivation, the gamma-irradiated pneumococcal vaccine retained cellular structure and elicited immunity against a broad array of pneumococcal proteins, positioning this vaccine well to stimulate robust immunity to pneumococcal disease.