A conserved antigen induces respiratory Th17-mediated serotype-independent protection against pneumococcal superinfection

Liu, X.; Van Maele, L.; Matarazzo, L.; Soulard, D.; Alves Duarte da Silva, V.; de Bakker, V.; Denereaz, J.; Bock, F. P.; Taschner, M.; Gruber, S.; Nizet, V.; Sirard, J.-C.; Veening, J.-W.

doi:10.1101/2023.07.07.548156

bioRxiv · 10.1101/2023.07.07.548156

A conserved antigen induces respiratory Th17-mediated serotype-independent protection against pneumococcal superinfection

Liu, X.·Van Maele, L.·Matarazzo, L.·Soulard, D.·Alves Duarte da Silva, V.·de Bakker, V.·Denereaz, J.·Bock, F. P.·Taschner, M.·Gruber, S.·Nizet, V.·Sirard, J.-C.·Veening, J.-W.

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Abstract

Several vaccines targeting bacterial pathogens show reduced efficacy in the context of intercurrent viral infection indicating a new vaccinology approach is required to protect against such superinfections. To find antigens for the human pathogen Streptococcus pneumoniae that are effective following influenza infection, we performed CRISPRi-seq in a murine model of superinfection and identified the highly conserved lafB gene as virulence factor. We show that LafB is a membrane-associated, intracellular protein that catalyzes the formation of galactosyl-glucosyl-diacylglycerol, a glycolipid we show is important for cell wall homeostasis. Respiratory vaccination with recombinant LafB, in contrast to subcutaneous vaccination, was highly protective against all serotypes in a murine model. In contrast to standard pneumococcal capsule-based conjugate vaccines, protection did not require LafB-specific antibodies but was dependent on airway CD4+ T helper 17 cells. Healthy human individuals can elicit LafB-specific immune responses, suggesting its merit as a universal pneumococcal vaccine antigen that remains effective following influenza infection. One-Sentence SummaryDiscovery of a universal pneumococcal vaccine protective during superinfection.

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Liu, X., Van Maele, L., Matarazzo, L., Soulard, D., Alves Duarte da Silva, V., de Bakker, V., Denereaz, J., Bock, F. P., Taschner, M., Gruber, S., Nizet, V., Sirard, J.-C., Veening, J.-W.. 2023-07-07. A conserved antigen induces respiratory Th17-mediated serotype-independent protection against pneumococcal superinfection. https://doi.org/10.1101/2023.07.07.548156

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