Safety and tolerability of conserved region vaccines vectored by plasmid DNA, simian adenovirus and modified vaccinia virus ankara administered to human immunodeficiency virus type 1-uninfected adults in a randomized, single-blind phase I trial
Autor: | Tomáš Hanke, A Rose, Lucy Dorrell, Mariarosaria Del Sorbo, Stefania Capone, Alison Crook, A P Black, Umar Ibrahimsa, Emma-Jo Hayton |
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Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Male
Human Immunodeficiency Virus Proteins lcsh:Medicine HIV Infections HIV Antibodies DNA vaccination Virus Replication chemistry.chemical_compound Medicine and Health Sciences Single-Blind Method lcsh:Science Booster Doses Conserved Sequence AIDS Vaccines Vaccines Vaccines Synthetic Recombinant Vaccines Multidisciplinary Viral Vaccine Immunogenicity Middle Aged Antiretroviral therapy 3. Good health Vaccination Tolerability Vaccination and immunization Female Research Article Plasmids Adult Attenuated Vaccines Adolescent Immunology Genetic Vectors Vaccinia virus Biology Virus Vaccine development Young Adult Inoculation Humans Reactogenicity Biology and life sciences lcsh:R Antibodies Neutralizing Virology HEK293 Cells chemistry HIV-1 Adenoviruses Simian lcsh:Q Vaccinia |
Zdroj: | PLoS ONE PLoS ONE, Vol 9, Iss 7, p e101591 (2014) |
ISSN: | 1932-6203 |
Popis: | Trial Design HIV-1 vaccine development has advanced slowly due to viral antigenic diversity, poor immunogenicity and recently, safety concerns associated with human adenovirus serotype-5 vectors. To tackle HIV-1 variation, we designed a unique T-cell immunogen HIVconsv from functionally conserved regions of the HIV-1 proteome, which were presented to the immune system using a heterologous prime-boost combination of plasmid DNA, a non-replicating simian (chimpanzee) adenovirus ChAdV-63 and a non-replicating poxvirus, modified vaccinia virus Ankara. A block-randomized, single-blind, placebo-controlled phase I trial HIV-CORE 002 administered for the first time candidate HIV-1- vaccines or placebo to 32 healthy HIV-1/2-uninfected adults in Oxford, UK and elicited high frequencies of HIV-1-specific T cells capable of inhibiting HIV-1 replication in vitro. Here, detail safety and tolerability of these vaccines are reported. Methods Local and systemic reactogenicity data were collected using structured interviews and study-specific diary cards. Data on all other adverse events were collected using open questions. Serum neutralizing antibody titres to ChAdV-63 were determined before and after vaccination. Results Two volunteers withdrew for vaccine-unrelated reasons. No vaccine-related serious adverse events or reactions occurred during 190 person-months of follow-up. Local and systemic events after vaccination occurred in 27/32 individuals and most were mild (severity grade 1) and predominantly transient ( |
Databáze: | OpenAIRE |
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