Michelle K. Brownlow

A Novel Staphylococcus aureus Vaccine: Iron Surface Determinant B Induces Rapid Antibody Responses in Rhesus Macaques and Specific Increased Survival in a Murine S. aureus Sepsis Model

ABSTRACT Staphylococcus aureus is a major cause of nosocomial infections worldwide, and the rate of resistance to clinically relevant antibiotics, such as methicillin, is increasing; furthermore, there has been an increase in the number of methicillin-resistant S. aureus community-acquired infections. Effective treatment and prevention strategies are urgently needed. We investigated the potential of the S. aureus surface protein iron surface determinant B (IsdB) as a prophylactic vaccine against S. aureus infection. IsdB is an iron-sequestering protein that is conserved in diverse S. aureus clinical isolates, both methicillin resistant and methicillin sensitive, and it is expressed on the surface of all isolates tested. The vaccine was highly immunogenic in mice when it was formulated with amorphous aluminum hydroxyphosphate sulfate adjuvant, and the resulting antibody responses were associated with reproducible and significant protection in animal models of infection. The specificity of the protective immune responses in mice was demonstrated by using an S. aureus strain deficient for IsdB and HarA, a protein with a high level of identity to IsdB. We also demonstrated that IsdB is highly immunogenic in rhesus macaques, inducing a more-than-fivefold increase in antibody titers after a single immunization. Based on the data presented here, IsdB has excellent prospects for use as a vaccine against S. aureus disease in humans.

Antibodies from Women Immunized with Gardasil ® Cross-Neutralize HPV 45 Pseudovirions

Human papillomavirus (HPV) types 6, 11, 16 and 18 L1 virus-like particles (VLPs) have been used to generate the prophylactic quadrivalent vaccine, Gardasil®. There is a high degree of homology within the L1 major capsid protein sequence of genital HPV types and it is therefore likely that there is a substantial degree of antigenic similarity of the surface exposed epitopes on the virion particles or on VLPs. It is possible then, that antibodies induced by immunization with Gardasil® could bind, and even neutralize HPV types that are closely related to the vaccine types. An investigation of antibody binding and neutralization was undertaken focusing on two members of the A7 species, HPV 18 and HPV 45. Polyclonal sera from Gardasil® recipients and from HPV 18 L1 VLP recipients were evaluated. Utilizing the pseudovirus neutralization assay developed by the National Cancer Institute, antibodies induced by the vaccines were found to cross-neutralize HPV 45 pseudovirions (PsV). Examination of a panel of monoclonal antibodies made against L1 VLPs revealed the presence of conformational, neutralizing epitopes on the surface of VLPs that may be shared between HPV 18 and HPV 45. These data demonstrate that Gardasil® immunization induces antibodies capable of neutralizing HPV 18 PsV and HPV 45 PsV in vitro.