title: Pneumococcal conjugate vaccination at birth in a high-risk setting: no evidence for neonatal T-cell tolerance.
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 CRM(197) 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.
authors.affiliation: Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, PO Box 855, West Perth WA 6872, Australia. Anita.vandenBiggelaar@Crucell.com
authors.forename: Anita H J
authors.initials: AH
authors.lastname: van den Biggelaar
authors.forename: William
authors.initials: W
authors.lastname: Pomat
authors.forename: Anthony
authors.initials: A
authors.lastname: Bosco
authors.forename: Suparat
authors.initials: S
authors.lastname: Phuanukoonnon
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Devitt
authors.forename: Marie A
authors.initials: MA
authors.lastname: Nadal-Sims
authors.forename: Peter M
authors.initials: PM
authors.lastname: Siba
authors.forename: Peter C
authors.initials: PC
authors.lastname: Richmond
authors.forename: Deborah
authors.initials: D
authors.lastname: Lehmann
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Holt
mesh_terms: D000367:Age Factors; D000907:Antibodies, Bacterial / Q000097:blood; D005260:Female; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D010219:Papua New Guinea; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D011247:Pregnancy; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D007074:Immunoglobulin G; D018793:Interleukin-13; D015848:Interleukin-5; D022242:Pneumococcal Vaccines; D007371:Interferon-gamma