Broad and Effective Protection against Staphylococcus aureus Is Elicited by a Multivalent Vaccine Formulated with Novel Antigens.

Jian Deng,Qiubin Lin,Xiaolei Wang,Richard Yi-Tsun Kao,Jian-Dong Huang,Kwok-Yung Yuen,Bao-Zhong Zhang,Kenth Gustafsson,Peng Gao,Drusilla L Burns

doi:10.1128/msphere.00362-19

Jian Deng, Qiubin Lin + Show 8 more

Open Access

https://doi.org/10.1128/msphere.00362-19

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Journal: mSphere	Publication Date: Sep 4, 2019
Citations: 8	License type: CC BY 4.0

Affiliation: University of Hong Kong, University College London

Abstract

The demand for a prophylactic vaccine against methicillin-resistant Staphylococcus aureus (MRSA) has motivated numerous dedicated research groups to design and develop such a vaccine. In this study, we have developed a multivalent vaccine, Sta-V5, composed of five conserved antigens involved in three important virulence mechanisms. This prototype vaccine conferred up to 100% protection against multiple epidemiologically relevant S. aureus isolates in five different murine disease models. The vaccine not only elicits functional antibodies that mediate opsonophagocytic killing of S. aureus but also mounts robust antigen-specific T-cell responses. In addition, our data implied that γδ T cells contribute to the protection induced by Sta-V5 in a murine skin infection model.IMPORTANCEStaphylococcus aureus infections, especially MRSA infections, are becoming a major global health issue and are resulting in mortality rates that are increasing every year. However, an effective vaccine is lacking due to the complexity of the infection process of S. aureus In this study, we found that the addition of two novel protein components to three well-studied vaccine candidates significantly improved the efficacy of the combined vaccine. Furthermore, the five-component vaccine not only elicits a robust antibody response but also induces cytokine secretion by T cells, making it a promising vaccine candidate to fill the void.

Highlights

IMPORTANCE Staphylococcus aureus infections, especially methicillin-resistant Staphylococcus aureus (MRSA) infections, are becoming a major global health issue and are resulting in mortality rates that are increasing every year
A previous study performed in our laboratory demonstrated that mice vaccinated with recombinant AdsA induced high titers of anti-AdsA antibodies and provided consistent protection in three mouse infection models under conditions of challenge with S. aureus clinical isolates [19]
The antigens selected target three key virulence and immunoevasion mechanisms employed by S. aureus in the infection process, and each antigen was capable of inducing protection to various degrees in different mouse models of S. aureus infection

Summary

Introduction

IMPORTANCE Staphylococcus aureus infections, especially MRSA infections, are becoming a major global health issue and are resulting in mortality rates that are increasing every year. An effective vaccine is lacking due to the complexity of the infection process of S. aureus. We found that the addition of two novel protein components to three well-studied vaccine candidates significantly improved the efficacy of the combined vaccine. Preventative vaccination is one of the most promising approaches to combat MRSA without any concerns regarding antibiotic resistance [3]. Previous studies have identified a myriad of virulence factors from S. aureus. Many of these virulence factors, along with surface proteins, have been evaluated as potential targets for vaccines [4]. Alpha-toxin [5], clumping factor A (ClfA) [6], fibronectin binding protein (FnBPA or FnBPB), Panton-Valentine leukocidin (PVL) [7], and protein A [8] and September/October 2019 Volume 4 Issue 5 e00362-19

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