Immunogenicity Comparison of a Next Generation Pneumococcal Conjugate Vaccine in Animal Models and Human Infants

Pediatr Infect Dis J. 2020 Jan;39(1):70-77. doi: 10.1097/INF.0000000000002522.


Background: Evaluation of a pneumococcal conjugate vaccine (PCV) in an animal model provides an initial assessment of the performance of the vaccine prior to evaluation in humans. Cost, availability, study duration, cross-reactivity and applicability to humans are several factors which contribute to animal model selection. PCV15 is an investigational 15-valent PCV which includes capsular polysaccharides from pneumococcal serotypes (ST) 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F all individually conjugated to cross-reactive material 197 (CRM197).

Methods: Immunogenicity of PCV15 was evaluated in infant rhesus macaques (IRM), adult New Zealand white rabbits (NZWR) and CD1 mice using multiplexed pneumococcal electrochemiluminescent (Pn ECL) assay to measure serotype-specific IgG antibodies, multiplexed opsonophagocytosis assay (MOPA) to measure serotype-specific functional antibody responses and bacterial challenge in mice to evaluate protection against a lethal dose of S. pneumoniae.

Results: PCV15 was immunogenic and induced both IgG and functional antibodies to all 15 vaccine serotypes in all animal species evaluated. PCV15 also protected mice from S. pneumoniae serotype 14 intraperitoneal challenge. Opsonophagocytosis assay (OPA) titers measured from sera of human infants vaccinated with PCV15 in a Phase 2 clinical trial showed a good correlation with that observed in IRM (rs=0.69, P=0.006), a medium correlation with that of rabbits (rs=0.49, P=0.06), and no correlation with that of mice (rs=0.04, P=0.89). In contrast, there was no correlation in serum IgG levels between human infants and animal models.

Conclusions: These results demonstrate that PCV15 is immunogenic across multiple animal species, with IRM and human infants showing the best correlation for OPA responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / blood
  • Antibodies, Bacterial / immunology
  • Cell Line, Tumor
  • Disease Models, Animal
  • Heptavalent Pneumococcal Conjugate Vaccine / immunology
  • Humans
  • Immunogenicity, Vaccine*
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Mice
  • Pneumococcal Infections / prevention & control*
  • Pneumococcal Vaccines / immunology*
  • Streptococcus pneumoniae / immunology*
  • Vaccines, Conjugate / immunology*


  • Antibodies, Bacterial
  • Heptavalent Pneumococcal Conjugate Vaccine
  • Immunoglobulin G
  • Pneumococcal Vaccines
  • Vaccines, Conjugate