Conserved molecular chaperone PrsA stimulates protective immunity against group A Streptococcus

TL;DR

This study explores PrsA1 and PrsA2 proteins as potential universal vaccine candidates against Group A Streptococcus, showing strong immune protection in mice.

Contribution

The study identifies PrsA1 and PrsA2 as highly conserved and non-cross-reactive vaccine candidates for Group A Streptococcus.

Findings

PrsA1 and PrsA2 are highly conserved across GAS isolates with minimal amino acid variation.

Antibodies targeting PrsA1/A2 enhance neutrophil killing and confer protective immunity in mice.

CFA-adjuvanted PrsA1/A2 immunization provides ~70% protection against invasive GAS infection.

Abstract

Group A Streptococcus (GAS) is a significant human pathogen that poses a global health concern. However, the development of a GAS vaccine has been challenging due to the multitude of diverse M-types and the risk of triggering cross-reactive immune responses. Our previous research has identified a critical role of PrsA1 and PrsA2, surface post-translational molecular chaperone proteins, in maintaining GAS proteome homeostasis and virulence traits. In this study, we aimed to further explore the potential of PrsA1 and PrsA2 as vaccine candidates for preventing GAS infection. We found that PrsA1 and PrsA2 are highly conserved among GAS isolates, demonstrating minimal amino acid variation. Antibodies specifically targeting PrsA1/A2 showed no cross-reactivity with human heart proteins and effectively enhanced neutrophil opsonophagocytic killing of various GAS serotypes. Additionally, passive transfer of PrsA1/A2-specific antibodies conferred protective immunity in infected mice. Compared to alum, immunization with CFA-adjuvanted PrsA1/A2 induced higher levels of Th1-associated IgG isotypes and complement activation and provided approximately 70% protection against invasive GAS challenge. These findings highlight the potential of PrsA1 and PrsA2 as universal vaccine candidates for the development of an effective GAS vaccine.

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