ABSTRACT
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.
Subject(s)
Immunogenicity, Vaccine , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines/immunology , Streptococcus pneumoniae/immunology , Vaccines, Conjugate/immunology , Animals , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Cell Line, Tumor , Disease Models, Animal , Heptavalent Pneumococcal Conjugate Vaccine/immunology , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , MiceABSTRACT
BACKGROUND: Pneumococcal disease remains a public health priority in adults. Safety and immunogenicity of 2 different formulations of 15-valent pneumococcal conjugate vaccine (PCV15) containing 13 serotypes included in 13-valent pneumococcal conjugate vaccine (PCV13) plus 2 additional serotypes (22F and 33F) were evaluated in adults ≥ 50 years (V114-006; NCT02547649). METHODS: A total of 690 subjects (230/arm) received a single dose of either PCV15 Formulation A, PCV15 Formulation B, or PCV13 and were followed for safety for 14 days postvaccination. Serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) and Immunoglobulin G (IgG) geometric mean concentrations (GMCs) were measured immediately prior and 30 days postvaccination. RESULTS: Both PCV15 formulations had generally comparable safety profiles to PCV13. Baseline IgG GMCs and OPA GMTs were comparable across vaccination groups. At 30 days postvaccination, both PCV15 formulations induced serotype specific antibodies to all 15 serotypes in the vaccine. IgG GMCs and OPA GMTs in recipients of either PCV15 formulation were non-inferior (≤ 2-fold margin) to those measured in recipients of PCV13 for shared serotypes and superior (> 1.0-fold difference) for serotypes unique to PCV15. Formulation B generally induced higher immune responses than Formulation A. CONCLUSION: In healthy adults ≥ 50 years of age, both new formulations of PCV15 displayed acceptable safety profiles and induced serotype-specific immune responses comparable to PCV13.
Subject(s)
Antibodies, Bacterial/blood , Immunogenicity, Vaccine , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines/immunology , Aged , Female , Healthy Volunteers , Humans , Immunoglobulin G/blood , Male , Middle Aged , Pneumococcal Vaccines/administration & dosage , Serogroup , Streptococcus pneumoniae , Vaccines, Conjugate/administration & dosage , Vaccines, Conjugate/immunologyABSTRACT
Using a large social media dataset and open-vocabulary methods from computational linguistics, we explored differences in language use across gender, affiliation, and assertiveness. In Study 1, we analyzed topics (groups of semantically similar words) across 10 million messages from over 52,000 Facebook users. Most language differed little across gender. However, topics most associated with self-identified female participants included friends, family, and social life, whereas topics most associated with self-identified male participants included swearing, anger, discussion of objects instead of people, and the use of argumentative language. In Study 2, we plotted male- and female-linked language topics along two interpersonal dimensions prevalent in gender research: affiliation and assertiveness. In a sample of over 15,000 Facebook users, we found substantial gender differences in the use of affiliative language and slight differences in assertive language. Language used more by self-identified females was interpersonally warmer, more compassionate, polite, and-contrary to previous findings-slightly more assertive in their language use, whereas language used more by self-identified males was colder, more hostile, and impersonal. Computational linguistic analysis combined with methods to automatically label topics offer means for testing psychological theories unobtrusively at large scale.
