Streptococcus pyogenes pharyngitis elicits diverse antibody responses to key vaccine antigens influenced by the imprint of past infections

Joshua Osowicki (), Hannah R. Frost, Kristy I. Azzopardi, Alana L. Whitcombe, Reuben McGregor, Lauren H. Carlton, Ciara Baker, Loraine Fabri, Manisha Pandey, Michael F. Good, Jonathan R. Carapetis, Mark J. Walker, Pierre R. Smeesters, Paul V. Licciardi, Nicole J. Moreland, Danika L. Hill () and Andrew C. Steer
Additional contact information
Joshua Osowicki: Murdoch Children’s Research Institute
Hannah R. Frost: Murdoch Children’s Research Institute
Kristy I. Azzopardi: Murdoch Children’s Research Institute
Alana L. Whitcombe: University of Auckland
Reuben McGregor: University of Auckland
Lauren H. Carlton: University of Auckland
Ciara Baker: Murdoch Children’s Research Institute
Loraine Fabri: Murdoch Children’s Research Institute
Manisha Pandey: Griffith University
Michael F. Good: Griffith University
Jonathan R. Carapetis: University of Western Australia
Mark J. Walker: The University of Queensland
Pierre R. Smeesters: Murdoch Children’s Research Institute
Paul V. Licciardi: University of Melbourne
Nicole J. Moreland: University of Auckland
Danika L. Hill: Monash University
Andrew C. Steer: Murdoch Children’s Research Institute

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Knowledge gaps regarding human immunity to Streptococcus pyogenes have impeded vaccine development. To address these gaps and evaluate vaccine candidates, we established a human challenge model of S. pyogenes pharyngitis. Here, we analyse antibody responses in serum and saliva against 19 antigens to identify characteristics distinguishing 19 participants who developed pharyngitis and 6 who did not. We show that pharyngitis elicits serum IgG responses to key vaccine antigens and a muted mucosal IgA response, whereas IgG responses are minimal and IgA responses more pronounced in participants without pharyngitis. Serum IgG responses to pharyngitis in adult participants resemble those in children and are inversely correlated with the magnitude of pre-existing responses. While a straightforward correlate of protection is not evident, baseline antibody signatures distinguish clinical and immunological outcomes following experimental challenge. This highlights the influence of a complex humoral imprint from previous exposure, relevant for interpreting immunogenicity in forthcoming vaccine trials.

Date: 2024
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DOI: 10.1038/s41467-024-54665-5

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