Osowicki Joshua, 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, Hill Danika L, Steer Andrew C
Tropical Diseases Research Group, Murdoch Children's Research Institute, Melbourne, VIC, Australia.
Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia.
Nat Commun. 2024 Dec 3;15(1):10506. doi: 10.1038/s41467-024-54665-5.
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.
关于人类对化脓性链球菌免疫的知识空白阻碍了疫苗的研发。为了填补这些空白并评估候选疫苗，我们建立了化脓性链球菌咽炎的人体激发模型。在此，我们分析血清和唾液中针对19种抗原的抗体反应，以确定区分19名患咽炎参与者和6名未患咽炎参与者的特征。我们发现，咽炎会引发血清IgG对关键疫苗抗原的反应以及微弱的黏膜IgA反应，而在未患咽炎的参与者中，IgG反应极小，IgA反应更为明显。成年参与者对咽炎的血清IgG反应与儿童相似，且与既往反应的强度呈负相关。虽然保护的直接关联尚不明显，但基线抗体特征可区分实验激发后的临床和免疫结果。这凸显了既往接触产生的复杂体液印记的影响，这对于解释即将进行的疫苗试验中的免疫原性具有重要意义。
