In vivo functional immunoprotection correlates for vaccines against invasive bacteria
Vaccine efficacy
DOI:
10.1016/j.vaccine.2024.01.018
Publication Date:
2024-01-16T09:15:28Z
AUTHORS (6)
ABSTRACT
Vaccination has significantly reduced the incidence of invasive infections caused by several bacterial pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. However, no vaccines are available for many other pathogens. A major hurdle in vaccine development is lack functional markers to quantify immunity eliminating pathogens during process infection. Based on our recent discovery liver as organ vaccine-induced clearance blood-borne virulent bacteria, we here describe a new evaluation system that quantitatively characterizes key features effective shuffling bacteria from blood circulation resident macrophage Kupffer cells (KCs) sinusoidal endothelial (LSECs) mouse septic infection model. This consists three related correlates or assays: pathogen bloodstream, trapping liver, capture KCs/LSECs. These readouts were consistently associated with serotype-specific immunoprotection levels 13-valent pneumococcal polysaccharide conjugate (PCV13) against lethal S. Gram-positive community-acquired humans. Furthermore, reliability sensitivity these reflecting efficacy verified whole cell Klebsiella pneumoniae Escherichia coli, two Gram-negative hospital-acquired infections. may be used evaluate immunoprotective potential candidates preclinical phase filling current technical gap between conventional vitro approaches (e.g. antibody production neutralization/opsonophagocytosis) survival immunized animals.
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