Pneumococcal conjugate vaccination at birth in a high-risk setting: No evidence for neonatal T-cell tolerance

• Published in: Vaccine Vol. 29; no. 33; pp. 5414 - 5420
• Main Authors: van den Biggelaar, Anita H.J, Pomat, William, Bosco, Anthony, Phuanukoonnon, Suparat, Devitt, Catherine J, Nadal-Sims, Marie A, Siba, Peter M, Richmond, Peter C, Lehmann, Deborah, Holt, Patrick G
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 26.07.2011; Elsevier; Elsevier Limited; Elsevier Science
• Subjects: Age; Age Factors; Allergy and Immunology; Antibodies, Bacterial - blood; Applied microbiology; Bacteriology; Biological and medical sciences; children; death; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Heptavalent Pneumococcal Conjugate Vaccine; Hospitals; Humans; Immune system; Immune Tolerance; Immunisation; Immunization; Immunogenicity; immunoglobulin G; Immunoglobulin G - blood; Infant; Infant, Newborn; Infants; interferon-gamma; Interferon-gamma - secretion; interleukin-13; Interleukin-13 - secretion; interleukin-5; Interleukin-5 - secretion; Leukocytes, Mononuclear - immunology; Medical research; mice; Microbiology; Miscellaneous; Mortality; Newborn; Papua New Guinea; Pneumococcal conjugate vaccine; Pneumococcal Vaccines - administration & dosage; Pneumococcal Vaccines - adverse effects; Pneumococcal Vaccines - immunology; Pregnancy; Proteins; risk; Safety; serotypes; Streptococcus pneumoniae; Studies; T-lymphocytes; T-Lymphocytes - immunology; Tetanus; vaccination; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Papua New Guinea; Pneumococcal conjugate vaccine; Newborn; Safety; Immunogenicity; Immunisation; Immunization; Vaccination; Vaccine; Streptococcus pneumoniae; Streptococcaceae; T-Lymphocyte; Bacteria; Micrococcales
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2011.05.065

Abstract Concerns about the risk of inducing immune deviation-associated “neonatal tolerance” as described in mice have restricted the widespread adoption of neonatal vaccination. The aim of this study was to demonstrate the immunological feasibility of neonatal pneumococcal conjugate vaccination (PCV) which could potentially protect high-risk infants in resource poor countries against severe pneumococcal disease and mortality in the early critical period of life. Papua New Guinean infants were randomized to be vaccinated with the 7-valent PCV (7vPCV) at birth, 1 and 2 months (neonatal group, n = 104) or at 1, 2 and 3 months of age (infant group, n = 105), or to not receive 7vPCV at all (control group, n = 109). Analysis of vaccine responses at 3 and 9 months of age demonstrated persistently higher type-1 (IFN-γ) and type-2 (IL-5 and IL-13) T-cell responses to the protein carrier CRM197 and IgG antibody titres to 7vPCV serotypes in children vaccinated with 7vPCV according to either schedule as compared to unvaccinated children. In a comprehensive immuno-phenotypic analysis at 9 months of age, no differences in the quantity or quality of vaccine-specific T cell memory responses were found between neonatal vaccinations versus children given their first PCV dose at one month. Hospitalization rates in the first month of life did not differ between children vaccinated with PCV at birth or not. These findings demonstrate that neonatal 7vPCV vaccination is safe and not associated with immunological tolerance. Neonatal immunisation schedules should therefore be considered in high-risk areas where this may result in improved vaccine coverage and the earliest possible protection against pneumococcal disease and death.