Journal Article

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

Triplett, Kathleen D., Daly, Seth M., Pokhrel, Srijana, Joyner, Jason A., Chackerian, Bryce, Elmore, Bradley O., Peabody, Julianne, Hall, Pamela R., Adebanjo, Diane, Peabody, David S.

2020

Overview

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

• Publisher: MDPI AG,MDPI
• Subject: Amino acids / Animals / Antibodies / Antibodies, Bacterial - blood / Antigens / Bacterial Toxins - immunology / Bacterial Toxins - pharmacology / Bacterial Vaccines - immunology / Bacterial Vaccines - pharmacology / Clinical trials / Disease Models, Animal / Domains / Epitopes / Female / Hemolysin Proteins - immunology / Hemolysin Proteins - pharmacology / Histocompatibility antigen HLA / Humans / Immune system / Immunity / Immunogenicity, Vaccine / Intoxication / Jurkat Cells / linear neutralizing domain / Lysis / Male / mice / Mice, Inbred BALB C / Neutralization Tests / Neutralizing / Pathogenesis / Pathogens / Peptides / Pore formation / Proteins / Skin - drug effects / Skin - immunology / Skin - microbiology / Skin - pathology / Staphylococcal Skin Infections - immunology / Staphylococcal Skin Infections - microbiology / Staphylococcal Skin Infections - pathology / Staphylococcal Skin Infections - prevention & control / Staphylococcus aureus / Staphylococcus aureus - drug effects / Staphylococcus aureus - immunology / Staphylococcus aureus - pathogenicity / Staphylococcus infections / Toxins / Vaccination / vaccine / Vaccines / Vaccines, Virus-Like Particle - immunology / Vaccines, Virus-Like Particle - pharmacology / Virulence / Virulence factors / Virus-like particles / Viruses / α-hemolysin