An epitope focused nanoparticle vaccine for MRSA and biodefense

DESCRIPTION provided by applicant Overall Staphylococcus aureus is a gram positive bacteria which possesses a multitude of virulence factors It is a frequent and severe pathogen in hospitals and of increasing concern in the community where it results in severe skin infections pneumonia bacterial endocarditis and sepsis A significant proportion of these infections are the result of methicillin resistant S aureus MRSA We have developed a highly immunogenic nanoparticle vaccine capable of rapidly eliciting antibody against the pore neutralizing determinant PND within alpha toxin AT a ubiquitous and critical virulence factor of MRSA Previous work has demonstrated that Ab against the PND is highly efficacious in preventing tissue injury and bacterial growth in a rigorous mouse dermonecrosis model and in protecting mice in a lethal model of S aureus pneumonia In this project we will develop a bivalent vaccine which targets both the PND as well as critical epitopes within both Staphylococcal enterotoxin B and C which have been shown to be particularly important virulence factors in MRSA infections but also have the potential to be formulated as bioweapons The vaccine emerging from these studies will be uniquely efficacious against MRSA infections and for protection against the potential for SEB and SEC intoxication PUBLIC HEALTH RELEVANCE Infections with methicillin resistant S aureus or MRSA constitute a public health imperative Emerging from these studies will be a uniquely efficacious nanoparticle vaccine against critical virulence factors which will be efficacious in preventing MRSA