title: Agglutination by anti-capsular polysaccharide antibody is associated with protection against experimental human pneumococcal carriage.
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.
authors: Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
authors: E
authors: E
authors: Mitsi
authors: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: A M
authors: AM
authors: Roche
authors: Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
authors: J
authors: J
authors: Reiné
authors: Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
authors: T
authors: T
authors: Zangari
authors: Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
authors: J T
authors: JT
authors: Owugha
authors: Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
authors: S H
authors: SH
authors: Pennington
authors: Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
authors: J F
authors: JF
authors: Gritzfeld
authors: Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
authors: A D
authors: AD
authors: Wright
authors: Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
authors: A M
authors: AM
authors: Collins
authors: Department of Pediatrics, Radboud University Medical Center, Nijmegen, the Netherlands.
authors: S
authors: S
authors: van Selm
authors: Department of Pediatrics, Radboud University Medical Center, Nijmegen, the Netherlands.
authors: M I
authors: MI
authors: de Jonge
authors: Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.|The Malawi Liverpool Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, Blantyre, Malawi.
authors: S B
authors: SB
authors: Gordon
authors: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.|Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
authors: J N
authors: JN
authors: Weiser
authors: Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
authors: D M
authors: DM
authors: Ferreira
mesh_terms: D000293:Adolescent; D000328:Adult; D000371:Agglutination; D000818:Animals; D000907:Antibodies, Bacterial / Q000378:metabolism*; D016667:Bacterial Capsules / Q000276:immunology; D002353:Carrier State; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011008:Pneumococcal Infections / Q000276:immunology* / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014611:Vaccination; D018074:Vaccines, Conjugate; D055815:Young Adult
chemical_list: C538862:13-valent pneumococcal vaccine; D000907:Antibodies, Bacterial; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate