A conserved antigen induces respiratory Th17-mediated broad serotype protection against pneumococcal superinfection.
Cell Host Microbe
; 32(3): 304-314.e8, 2024 Mar 13.
Article
en En
| MEDLINE
| ID: mdl-38417443
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Infecciones Neumocócicas
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Vacunas contra la Influenza
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Sobreinfección
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Gripe Humana
Límite:
Animals
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Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article