Abstract
The ability of pneumococcal conjugate vaccine (PCV) to decrease transmission by blocking the acquisition of colonization has been attributed to herd immunity. We describe the role of mucosal immunoglobulin G (IgG) to capsular polysaccharide (CPS) in mediating protection from carriage, translating our findings from a murine model to humans. We used a flow cytometric assay to quantify antibody-mediated agglutination demonstrating that hyperimmune sera generated against an unencapsulated mutant was poorly agglutinating. Passive immunization with this antiserum was ineffective to block acquisition of colonization compared to agglutinating antisera raised against the encapsulated parent strain. In the human challenge model, samples were collected from PCV and control-vaccinated adults. In PCV-vaccinated subjects, IgG levels to CPS were increased in serum and nasal wash (NW). IgG to the inoculated strain CPS dropped in NW samples after inoculation suggesting its sequestration by colonizing pneumococci. In post-vaccination NW samples pneumococci were heavily agglutinated compared with pre-vaccination samples in subjects protected against carriage. Our results indicate that pneumococcal agglutination mediated by CPS-specific antibodies is a key mechanism of protection against acquisition of carriage. Capsule may be the only vaccine target that can elicit strong agglutinating antibody responses, leading to protection against carriage acquisition and generation of herd immunity.
Highlights
The human nasal mucosa forms the first line of defence against respiratory pathogens
We recently reported that pneumococcal conjugate vaccine (PCV) conferred a 78% reduction in carriage acquisition compared to a control group following inoculation of adults with live type 6B pneumococci in an experimental human pneumococcal carriage (EHPC) study.[9]
Our focus was on immunoglobulin G (IgG) because it is generated in high concentrations in response to systemic immunization and has been shown to be sufficient to promote agglutination on the mucosal surface.[5]
Summary
The human nasal mucosa forms the first line of defence against respiratory pathogens. Some of these pathogens such as Streptococcus pneumoniae (the pneumococcus) can asymptomatically colonize the upper respiratory tract (the carrier state).[1] most episodes of pneumococcal carriage do not result in disease, the organism may gain access to normally sterile sites in its human host from its niche on the mucosal surfaces of the upper airways.[2] Mucosal immune responses, have a critical role in the defence against pneumococcal infections as they dictate the outcome of host–pathogen interactions at the mucosa. Levels were measured in serum and nasal wash samples in (a–d) PCV-vaccinated subjects and (e–h) control group using WHO standardised ELISA. Results were analyzed using one-way ANOVA test and Bonferroni’s multiple comparison tests. ***Po0.0001, **Po0.005, *Po0.01
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