Safety and immunogenicity of a trivalent recombinant PcpA,PhtD, and PlyD1 pneumococcal protein vaccine in adults,toddlers, and infants: A phase I randomized controlled study |
| |
| Institution: | 1. International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh;2. Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA;3. Sanofi Pasteur, Swiftwater, PA, USA;1. Division of Pulmonology, Department of Internal Medicine, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa;2. Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;3. Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa;1. Rochester General Hospital Research Institute, Rochester General Hospital, Rochester, NY 14621, USA;2. Sanofi Pasteur, 1541 Ave Marcel Merieux, 69280 Marcy L’Etoile, France;1. Laboratory for Clinical Research on Infectious Disease, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Japan;2. Division of Infection Control and Prevention, Osaka University Graduate School of Medicine, Japan;3. National Institute of Biomedical Innovation, Japan;4. Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Japan;5. Department of Infectious Diseases, Keio University School of Medicine, Japan;6. Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Japan;7. Department of Microbiology, University of Alabama at Birmingham, USA;1. Laboratório Especial de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, Brazil;2. Programa de Pós Graduação Interunidades em Biotecnologia USP-IPT-IB, São Paulo, Brazil;3. Laboratório de Biologia Molecular de Microrganismos, Universidade São Francisco, Bragança Paulista, Brazil;1. Vaccine Immunotherapeutics, Pfizer, 10777 Science Center Drive, La Jolla, CA 92121, USA;2. Vaccine Immunotherapeutics, Pfizer, 200-340 Terry Fox Drive, Ottawa, Ontario K2K3A2, Canada;3. Vaccine Research & Development, Pfizer, 401 North Middletown Road, Pearl River, NY 10965, USA;1. Saint Louis University, School of Medicine, Center for Vaccine Development, St. Louis, MO, USA;2. EMMES Corporation, Rockville, MD, USA;3. The Biodesign Institute, Arizona State University, Tempe, AZ, USA;4. Independent Contractor, St. Louis, MO, USA |
| |
| Abstract: | BackgroundPneumococcal protein vaccines (PPrVs) may provide improved protection over currently available polysaccharide and conjugated polysaccharide vaccines. Here, we examined the safety and immunogenicity of a trivalent recombinant PPrV containing PcpA, PhtD, and PlyD1.MethodsThis was a phase I, single-center, randomized, observer-blind study with safety review between cohorts. Adults (18–50 years; n = 30) and then toddlers (12–13 months; n = 30) were randomized 2:1 to receive aluminum-adjuvanted trivalent PPrV (PPrV + adj) containing 50 μg per antigen or placebo. Infants (42–49 days; n = 220) were next randomized to be injected at 6, 10, and 14 weeks of age with 10 μg PPrV + adj or placebo (n = 60; 2:1); 25 μg PPrV + adj, 25 μg unadjuvanted PPrV, or placebo (n = 100; 2:2:1); and 50 μg PPrV + adj or placebo (n = 60; 2:1). Solicited reactions were recorded for 7 days and unsolicited adverse events for 30 days after each vaccination. Concentrations of antibodies to the three vaccine antigens were measured by enzyme-linked immunosorbent assay.ResultsTenderness/pain was the most frequent injection-site reaction. Abnormal crying and irritability (infants), loss of appetite (toddlers), and headache, malaise, and myalgia (adults) were the most frequent systemic reactions. Reactions were mostly mild or moderate, resolved within 3 days, were not adjuvant- or dose-dependent, and were not increased by repeated vaccination. No immediate adverse events, hypersensitivity reactions, or treatment-related serious adverse events were reported. In all PPrV + adj cohorts, at least 75% of subjects had a ≥2-fold increase in all three antibody concentrations. In infants, antibody concentrations were higher with PPrV + adj than with unadjuvanted PPrV, higher with three than two vaccinations, and similar at the different vaccine doses.ConclusionsThe candidate trivalent PPrV was safe and immunogenic in adults, toddlers, and infants. Addition of aluminum adjuvant improved immunogenicity in infants without changing the safety profile. |
| |
| Keywords: | Pneumococcal vaccine Infants Phase I clinical trials AE"} {"#name":"keyword" "$":{"id":"kw0035"} "$$":[{"#name":"text" "_":"adverse event CI"} {"#name":"keyword" "$":{"id":"kw0045"} "$$":[{"#name":"text" "_":"confidence interval ELISA"} {"#name":"keyword" "$":{"id":"kw0055"} "$$":[{"#name":"text" "_":"enzyme-linked immunosorbent assay EU"} {"#name":"keyword" "$":{"id":"kw0065"} "$$":[{"#name":"text" "_":"ELISA units GMC"} {"#name":"keyword" "$":{"id":"kw0075"} "$$":[{"#name":"text" "_":"geometric mean antibody concentration PcpA"} {"#name":"keyword" "$":{"id":"kw0085"} "$$":[{"#name":"text" "_":"pneumococcal choline-binding protein A PhtD"} {"#name":"keyword" "$":{"id":"kw0095"} "$$":[{"#name":"text" "_":"pneumococcal histidine triad protein D PlyD1"} {"#name":"keyword" "$":{"id":"kw0105"} "$$":[{"#name":"text" "_":"detoxified Ply derivative PPrV"} {"#name":"keyword" "$":{"id":"kw0115"} "$$":[{"#name":"text" "_":"pneumococcal protein vaccine aluminum-adjuvanted candidate trivalent pneumococcal vaccine SAE"} {"#name":"keyword" "$":{"id":"kw0135"} "$$":[{"#name":"text" "_":"serious adverse event |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
