Scientific Publications by FDA Staff

Clin Vaccine Immunol 2014 May;21(5):622-7

Role of antibodies in protection elicited by active vaccination with genetically inactivated alpha hemolysin in a mouse model of staphylococcus aureus skin and soft tissue infections.

Mocca CP, Brady RA, Burns DL

Due to the emergence of highly virulent community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) infections, S. aureus has become a major threat to public health. A majority of CA-MRSA skin and soft tissue infections in the U.S. are caused by USA300 strains that are known to produce high levels of alpha hemolysin (Hla). Therefore, vaccines are currently being developed that contain inactivated forms of this toxin. In this study, we sought to determine the immune mechanisms of protection for this antigen using a vaccine composed of a genetically inactivated form of Hla (HlaH35L). Using a murine model of skin and soft tissue infections (SSTI), we found that BALB/c mice were protected by vaccination with HlaH35L, however Jh mice, which are deficient in mature B lymphocytes and which lack IgM and IgG in their sera, were not protected. Passive immunization with anti-HlaH35L antibodies conferred protection against bacterial colonization. Moreover we found a positive correlation between total antibody concentration induced by active vaccination and reduced bacterial levels. Animals that developed detectable neutralizing antibody titers after active vaccination were significantly protected from infection. These data demonstrate that antibodies to Hla represent the major mechanism of protection afforded by active vaccination with inactivated Hla in this murine model of SSTI and antibody levels correlate with protection in this disease model. These results provide important information for future development and evaluation of S. aureus vaccines.