Back to Search
Start Over
Phase I Safety and Immunogenicity Evaluation of MVA-CMDR, a Multigenic, Recombinant Modified Vaccinia Ankara-HIV-1 Vaccine Candidate.
- Source :
- PLoS ONE; 2010, Vol. 5 Issue 11, p1-15, 15p
- Publication Year :
- 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; 10<superscript>7</superscript> or 10<superscript>8</superscript> pfu) or intradermally (ID; 10<superscript>6</superscript> or 10<superscript>7</superscript> 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 <superscript>51</superscript>Cr-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/10<superscript>6</superscript> PBMC at 10<superscript>8</superscript> pfu IM), but high in response rate (70% <superscript>51</superscript>Cr-release positive; 90% Elispot positive; 100% ICS positive, at 10<superscript>8</superscript> pfu IM); (ii) predominantly HIV Env-specific CD4<superscript>+</superscript> 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 10<superscript>8</superscript> 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 10<superscript>8</superscript> pfu IM). Conclusions/Significance: MVA-CMDR delivered both intramuscularly and intradermally was safe, well-tolerated and elicited durable cell-mediated and humoral immune responses. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 5
- Issue :
- 11
- Database :
- Complementary Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 59287809
- Full Text :
- https://doi.org/10.1371/journal.pone.0013983