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 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 to 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.

Pneumococcal Capsular Polysaccharide Immunity in the Elderly

“…In mice, passive transfer of antibodies leads to agglutination of bacteria following an intranasal challenge, which causes the bacteria to clump and become more vulnerable to mucociliary clearance (48). Pneumococcal antibody-mediated agglutination has also been demonstrated in humans following vaccination with pneumococcal conjugate vaccine (PCV) (49). In that study, naturally acquired antibodies were present in the nasopharynx prior to vaccination but not at levels sufficient to induce agglutination.…”

“…In young adults, systemic immunization with PCV13 leads to high concentrations of antipneumococcal IgG in serum, which spills over into the nasal mucosal compartment and can, by virtue of its agglutinating properties, prevent the development of pneumococcal colonization (49). This is likely to be the mechanism for the reduction of pneumococcal colonization following infant vaccination.…”

Streptococcus pneumoniae: transmission, colonization and invasion

“…Such memory B cells can quickly differentiate into antibody-secreting plasma cells following antigen exposure. Furthermore, the effectiveness of S. pneumoniae agglutination of airway secretions after PCV vaccination correlates with protection during experimental human colonization 28 . An additional effect of immunity demonstrated in the infant mouse model is a decrease in shedding by index pups 24 .…”

Genetic background impacts vaccine-induced reduction of pneumococcal colonization

“…In this process, antibodies agglutinate bacterial cells and accelerate clearance from the nasopharyngeal mucosa [22,32]. Recently, our group observed that incubation of PspA-specific antibodies with pneumococci led to agglutination [21].…”