MF59- and Al(OH)3-adjuvanted Staphylococcus aureus (4C-Staph) vaccines induce sustained protective humoral and cellular immune responses, with a critical role for effector CD4 T cells at low antibody titers.

MF59- and Al(OH)3-adjuvanted Staphylococcus aureus (4C-Staph) vaccines induce sustained protective humoral and cellular immune responses, with a critical role for effector CD4 T cells at low antibody titers.

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Staphylococcus aureus (S.aureus) is an important opportunistic pathogen that may cause invasive life-threatening infections like sepsis and pneumonia.Due to increasing antibiotic-resistance, the development of an effective vaccine against S.

aureus is needed.Although a correlate of protection against staphylococcal diseases is not yet established, several findings suggest that both antibodies and CD4 T cells might contribute to optimal immunity.In this study, we show that adjuvanting a multivalent vaccine (4C-Staph) with MF59, an oil-in-water emulsion licensed in human vaccines, further potentiated antigen-specific IgG titers and CD4 T cell responses compared to alum and conferred protection in the peritonitis model of S.

aureus infection.Moreover, we showed PEPPERMINT TOOTHPASTE that MF59- and alum-adjuvanted 4C-Staph vaccines induced persistent antigen-specific humoral and T cell responses, and protected mice from infection up to 4 months after immunization.Furthermore, 4C-Staph formulated with MF59 was used to investigate which immune compartment is involved in vaccine-induced protection.

Using CD4 T cell-depleted mice or B cell deficient mice, we demonstrated that both T and B cell responses contributed to 4C-Staph vaccine-mediated protective immunity.However, the role of CD4 T cells seemed more bag evident in the presence of low antibody responses.This study provides preclinical data further supporting the use of the adjuvanted 4C-Staph vaccines against S.

aureus diseases, and provides critical insights on the correlates of protective immunity necessary to combat this pathogen.