Streptococcus pyogenes pharyngitis elicits diverse antibody responses to key vaccine antigens influenced by the imprint of past infections
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Frost, Hannah R
Azzopardi, Kristy I
Whitcombe, Alana L
McGregor, Reuben
Carlton, Lauren H
Baker, Ciara
Fabri, Loraine
Pandey, Manisha
Good, Michael F
Carapetis, Jonathan R
Walker, Mark J
Smeesters, Pierre R
Licciardi, Paul V
Moreland, Nicole J
et al.
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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.
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Nat Commun
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15
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© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
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Epidemiology
Immunology
Medical bacteriology
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Osowicki, J; Frost, HR; Azzopardi, KI; Whitcombe, AL; McGregor, R; Carlton, LH; Baker, C; Fabri, L; Pandey, M; Good, MF; Carapetis, JR; Walker, MJ; Smeesters, PR; Licciardi, PV; Moreland, NJ; Hill, DL; Steer, AC, Streptococcus pyogenes pharyngitis elicits diverse antibody responses to key vaccine antigens influenced by the imprint of past infections., Nat Commun, 2024, 15, pp. 10506