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Phase I safety and immunogenicity evaluation of MVA-CMDR, a multigenic, recombinant modified vaccinia Ankara-HIV-1 vaccine candidate.
- Source :
-
PloS one [PLoS One] 2010 Nov 15; Vol. 5 (11), pp. e13983. Date of Electronic Publication: 2010 Nov 15. - 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&#95;AE, which predominates in Thailand. The objective was to evaluate safety and immunogenicity of MVA-CMDR in human volunteers in the US and Thailand.<br />Methodology/principal Findings: MVA-CMDR or placebo was administered intra-muscularly (IM; 10(7) or 10(8) pfu) or intradermally (ID; 10(6) or 10(7) 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 (51)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(6) PBMC at 10(8) pfu IM), but high in response rate (70% (51)Cr-release positive; 90% Elispot positive; 100% ICS positive, at 10(8) 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 10(8) 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(8) pfu IM).<br />Conclusions/significance: MVA-CMDR delivered both intramuscularly and intradermally was safe, well-tolerated and elicited durable cell-mediated and humoral immune responses.<br />Trial Registration: ClinicalTrials.gov NCT00376090.
- Subjects :
- AIDS Vaccines administration & dosage
Adult
Dose-Response Relationship, Drug
Enzyme-Linked Immunosorbent Assay
Fatigue etiology
Female
Flow Cytometry
Genetic Vectors genetics
HIV Infections prevention & control
HIV-1 genetics
Headache etiology
Human Immunodeficiency Virus Proteins genetics
Humans
Immunity, Cellular drug effects
Immunity, Cellular immunology
Immunity, Humoral drug effects
Immunity, Humoral immunology
Injections, Intradermal
Injections, Intramuscular
Male
Nausea etiology
Recombination, Genetic
Thailand
United States
Vaccination adverse effects
Vaccination methods
Vaccinia virus genetics
AIDS Vaccines immunology
HIV Infections immunology
HIV-1 immunology
Human Immunodeficiency Virus Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 5
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 21085591
- Full Text :
- https://doi.org/10.1371/journal.pone.0013983