title: Streptococcus pneumoniaeTransmission Is Blocked by Type-Specific Immunity in an Infant Mouse Model.
abstract: Epidemiological studies onStreptococcus pneumoniaeshow that rates of carriage are highest in early childhood and that the major benefit of the pneumococcal conjugate vaccine (PCV) is a reduction in the incidence of nasopharyngeal colonization through decreased transmission within a population. In this study, we sought to understand how anti-S. pneumoniaeimmunity affects nasal shedding of bacteria, the limiting step in experimental pneumococcal transmission. Using an infant mouse model, we examined the role of immunity (passed from mother to pup) on shedding and within-litter transmission ofS. pneumoniaeby pups infected at 4 days of life. Pups from both previously colonized immune and PCV-vaccinated mothers had higher levels of anti-S. pneumoniaeIgG than pups from non-immune or non-vaccinated mothers and shed significantly fewerS. pneumoniaeover the first 5 days of infection. By setting up cross-foster experiments, we demonstrated that maternal passage of antibody to pups eitherin uteroor post-natally decreasesS. pneumoniaeshedding. Passive immunization experiments showed that type-specific antibody to capsular polysaccharide is sufficient to decrease shedding and that the agglutinating function of immunoglobulin is required for this effect. Finally, we established that anti-pneumococcal immunity and anti-PCV vaccination block host-to-host transmission ofS. pneumoniaeMoreover, immunity in either the donor or recipient pups alone was sufficient to reduce rates of transmission, indicating that decreased shedding and protection from acquisition of colonization are both contributing factors. Our findings provide a mechanistic explanation for the reduced levels ofS. pneumoniaetransmission between hosts immune from prior exposure and among vaccinated children.IMPORTANCERates of carriage of the bacterial pathogenStreptococcus pneumoniaeare highest among young children, and this is the target group for the pneumococcal conjugate vaccine (PCV). Epidemiological studies have suggested that a major benefit of the PCV is a reduction in host-to-host transmission, which also protects the non-vaccinated population ("herd immunity"). In this study, we examined the role of anti-pneumococcal immunity on nasal shedding and transmission of the pathogen using an infant mouse model. We found that shedding is decreased and transmission is blocked by anti-pneumococcal immunity and PCV vaccination. Additionally, transmission rates decreased if either the infected or contact pups were immune, indicating that reduced shedding and protection from the establishment of colonization are both contributing factors. Our study provides a mechanistic explanation for the herd immunity effect seen after the introduction of PCV and identifies potential points of intervention, which may have implications for future vaccine development.
authors.affiliation: Department of Microbiology, New York University School of Medicine, New York, New York, USA.
authors.forename: Tonia
authors.initials: T
authors.lastname: Zangari
authors.affiliation: Department of Microbiology, New York University School of Medicine, New York, New York, USA.|School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Microbiology, New York University School of Medicine, New York, New York, USA jeffrey.weiser@nyumc.org.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Weiser
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000907:Antibodies, Bacterial / Q000097:blood; D057138:Bacterial Shedding; D004195:Disease Models, Animal; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D007112:Immunity, Maternally-Acquired; D007116:Immunization, Passive; D051379:Mice; D011008:Pneumococcal Infections / Q000635:transmission*; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D000907:Antibodies, Bacterial
keywords: PCV; Streptococcus pneumoniae; immunity; transmission