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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.

Original publication

DOI

10.1038/mi.2016.71

Type

Journal article

Journal

Mucosal Immunol

Publication Date

03/2017

Volume

10

Pages

385 - 394

Keywords

Adolescent, Adult, Agglutination, Animals, Antibodies, Bacterial, Bacterial Capsules, Carrier State, Female, Humans, Immunization, Passive, Male, Mice, Mice, Inbred C57BL, Middle Aged, Pneumococcal Infections, Pneumococcal Vaccines, Streptococcus pneumoniae, Vaccination, Vaccines, Conjugate, Young Adult