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

Author

Listed:
  • Joshua Osowicki

    (Murdoch Children’s Research Institute
    University of Melbourne
    Royal Children’s Hospital Melbourne)

  • Hannah R. Frost

    (Murdoch Children’s Research Institute)

  • Kristy I. Azzopardi

    (Murdoch Children’s Research Institute)

  • Alana L. Whitcombe

    (University of Auckland
    The University of Auckland)

  • Reuben McGregor

    (University of Auckland
    The University of Auckland)

  • Lauren H. Carlton

    (University of Auckland
    The University of Auckland)

  • Ciara Baker

    (Murdoch Children’s Research Institute)

  • Loraine Fabri

    (Murdoch Children’s Research Institute
    Université libre de Bruxelles
    Université libre de Bruxelles)

  • Manisha Pandey

    (Griffith University)

  • Michael F. Good

    (Griffith University)

  • Jonathan R. Carapetis

    (University of Western Australia
    University of Western Australia
    Perth Children’s Hospital)

  • Mark J. Walker

    (The University of Queensland
    The University of Queensland
    The University of Queensland)

  • Pierre R. Smeesters

    (Murdoch Children’s Research Institute
    University of Melbourne
    Université libre de Bruxelles
    Université libre de Bruxelles)

  • Paul V. Licciardi

    (University of Melbourne
    Murdoch Children’s Research Institute)

  • Nicole J. Moreland

    (University of Auckland
    The University of Auckland)

  • Danika L. Hill

    (Monash University)

  • Andrew C. Steer

    (Murdoch Children’s Research Institute
    University of Melbourne
    Royal Children’s Hospital Melbourne)

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.

Suggested Citation

  • 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. Carape, 2024. "Streptococcus pyogenes pharyngitis elicits diverse antibody responses to key vaccine antigens influenced by the imprint of past infections," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54665-5
    DOI: 10.1038/s41467-024-54665-5
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    References listed on IDEAS

    as
    1. Jeremy Anderson & Samira Imran & Hannah R. Frost & Kristy I. Azzopardi & Sedigheh Jalali & Boris Novakovic & Joshua Osowicki & Andrew C. Steer & Paul V. Licciardi & Daniel G. Pellicci, 2022. "Immune signature of acute pharyngitis in a Streptococcus pyogenes human challenge trial," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    2. Dennis Schaefer-Babajew & Zijun Wang & Frauke Muecksch & Alice Cho & Maximilian Loewe & Melissa Cipolla & Raphael Raspe & Brianna Johnson & Marie Canis & Justin DaSilva & Victor Ramos & Martina Turroj, 2023. "Antibody feedback regulates immune memory after SARS-CoV-2 mRNA vaccination," Nature, Nature, vol. 613(7945), pages 735-742, January.
    Full references (including those not matched with items on IDEAS)

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