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Phase I Safety andImmunogenicityEvaluation ofMVA-CMDR, aMultigenic,Recombinant ModifiedVaccinia Ankara-HIV-1Vaccine Candidate Jeffrey R. CurrierViseth NgauyMark de Souza2010 год

Phase I Safety and Immunogenicity Evaluation of MVA-CMDR, a Multigenic, Recombinant Modified Vaccinia Ankara-HIV-1 Vaccine Candidate
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Аннотация: Background We conducted a Phase I randomized, dose-escalation, route-comparison trial of MVA-CMDR, a candidate HIV-1 vaccine based on a recombinant modified vaccinia Ankara viral vector expressing HIV-1 genes env/gag/pol. The HIV sequences were derived from circulating recombinant form CRF01_AE, which predominates in Thailand. The objective was to evaluate safety and immunogenicity of MVA-CMDR in human volunteers in the US and Thailand. Methodology/Principal Findings MVA-CMDR or placebo was administered intra-muscularly (IM; 107 or 108 pfu) or intradermally (ID; 106 or 107 pfu) at months 0, 1 and 3, to 48 healthy volunteers at low risk for HIV-1 infection. Twelve volunteers in each dosage group were randomized to receive MVA-CMDR or placebo (10∶2). Volunteers were actively monitored for local and systemic reactogenicity and adverse events post vaccination. Cellular immunogenicity was assessed by a validated IFNγ Elispot assay, an intracellular cytokine staining assay, lymphocyte proliferation and a 51Cr-release assay. Humoral immunogenicity was assessed by ADCC for gp120 and binding antibody ELISAs for gp120 and p24. MVA-CMDR was safe and well tolerated with no vaccine related serious adverse events. Cell-mediated immune responses were: (i) moderate in magnitude (median IFNγ Elispot of 78 SFC/106 PBMC at 108 pfu IM), but high in response rate (70% 51Cr-release positive; 90% Elispot positive; 100% ICS positive, at 108 pfu IM); (ii) predominantly HIV Env-specific CD4+ T cells, with a high proliferative capacity and durable for at least 6 months (100% LPA response rate by the IM route); (iv) dose- and route-dependent with 108 pfu IM being the most immunogenic treatment. Binding antibodies against gp120 and p24 were detectable in all vaccination groups with ADCC capacity detectable at the highest dose (40% positive at 108 pfu IM). Conclusions/Significance MVA-CMDR delivered both intramuscularly and intradermally was safe, well-tolerated and elicited durable cell-mediated and humoral immune responses. Trial Registration ClinicalTrials.gov NCT00376090
Год издания: 2010
Авторы: Jeffrey R. Currier, Viseth Ngauy, Mark de Souza, Silvia Ratto‐Kim, Josephine H. Cox, Victoria R. Polonis, Patricia L. Earl, Bernard Moss, Sheila A. Peel, Bonnie M. Slike, Somchai Sriplienchan, P Thongcharoen, Robert Paris, Merlin L. Robb, Jérôme H. Kim, Nelson L. Michael, Mary Marovich
Издательство: Public Library of Science
Источник: PLoS ONE
Ключевые слова: HIV Research and Treatment, vaccines and immunoinformatics approaches, Herpesvirus Infections and Treatments
Другие ссылки: PLoS ONE (PDF)
PLoS ONE (HTML)
DOAJ (DOAJ: Directory of Open Access Journals) (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
OPAL (Open@LaTrobe) (La Trobe University) (PDF)
OPAL (Open@LaTrobe) (La Trobe University) (HTML)
PubMed (HTML)