Vaccination with VLPs Presenting a Linear Neutralizing Domain of S. aureus Hla Elicits Protective Immunity

• DOI: 10.3390/toxins12070450
• Publication Date: 2020-07-22T09:10:30Z
• Authors: Jason A. Joyner; Seth M. Daly; Julianne Peabody; Kathleen D. Triplett; Srijana Pokhrel; Bradley O. Elmore; Diane Adebanjo; David S. Peabody; Bryce Chackerian; Pamela R. Hall
• Keywords: Male; 0301 basic medicine; Staphylococcus aureus; mice; Bacterial Toxins; <i>Staphylococcus aureus</i>; virus-like particles; Article; Epitopes; Hemolysin Proteins; Jurkat Cells; 03 medical and health sciences; Immunogenicity, Vaccine; Neutralization Tests; vaccine; Animals; Humans; Vaccines, Virus-Like Particle; Skin; Mice, Inbred BALB C; Vaccination; R; Antibodies, Bacterial; 3. Good health; α-hemolysin; Disease Models, Animal; linear neutralizing domain; Bacterial Vaccines; Medicine; Female; Staphylococcal Skin Infections

The pore-forming cytotoxin α-hemolysin, or Hla, is a critical Staphylococcus aureus virulence factor that promotes infection by causing tissue damage, excessive inflammation, and lysis of both innate adaptive immune cells, among other cellular targets. In this study, we asked whether virus-like particle (VLP)-based vaccine targeting Hla could attenuate S. Hla-mediated pathogenesis. VLPs are versatile platforms can be used to display target antigens in multivalent array, typically resulting the induction high titer, long-lasting antibody responses. present describe first VLP-based vaccines Hla. Vaccination with either two displaying 21 amino-acid linear neutralizing domain (LND) protected male female mice from subcutaneous challenge, evident reduction lesion size neutrophil influx site intoxication. Antibodies elicited VLP-LND vaccination bound LND peptide native toxin, effectively preventing toxin-mediated cells. We anticipate these novel promising being part multi-component reduce severity infection.