A conserved antigen induces respiratory Th17-mediated broad serotype protection against pneumococcal superinfection
Xue Liu, Laurye Van Maele, Laura Matarazzo, Daphnée Soulard, Vinicius Alves Duarte da Silva, Vincent de Bakker, Julien Dénéréaz, Florian Patrick Bock, Michael Täschner, Jinzhao Ou, Stephan Gruber, Victor Nizet, Jean‐Claude Sirard, Jan‐Willem Veening
Abstract
Several vaccines targeting bacterial pathogens show reduced efficacy upon concurrent viral infection, indicating that a new vaccinology approach is required. To identify 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 conserved lafB gene as crucial for virulence. We show that LafB is a membrane-associated, intracellular protein that catalyzes the formation of galactosyl-glucosyl-diacylglycerol, a glycolipid important for cell wall homeostasis. Respiratory vaccination with recombinant LafB, in contrast to subcutaneous vaccination, was highly protective against S. pneumoniae serotypes 2, 15A, and 24F in a murine model. In contrast to standard capsule-based 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, indicating LafB antigenicity in humans. Collectively, these findings present a universal pneumococcal vaccine antigen that remains effective following influenza infection.