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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/28420
Title: Phase I safety and immunogenicity evaluation of MVA-CMDR, a multigenic, recombinant modified vaccinia ankara-HIV-1 vaccine candidate
Authors: Jeffrey R. Currier
Viseth Ngauy
Mark S. de Souza
Silvia Ratto-Kim
Josephine H. Cox
Victoria R. Polonis
Patricia Earl
Bernard Moss
Sheila Peel
Bonnie Slike
Somchai Sriplienchan
Prasert Thongcharoen
Robert M. Paris
Merlin L. Robb
Jerome Kim
Nelson L. Michael
Mary A. Marovich
US MIlitary HIV Research Program/Henry M. Jackson Foundation
Armed Forces Research Institute of Medical Sciences, Thailand
International AIDS Vaccine Initiative
National Institute of Allergy and Infectious Diseases
Mahidol University
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology;Medicine
Issue Date: 9-Dec-2010
Citation: PLoS ONE. Vol.5, No.11 (2010)
Abstract: 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 routedependent 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.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=78649733251&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/28420
ISSN: 19326203
Appears in Collections:Scopus 2006-2010

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