D Carter

D Clarke

I Frank

J Eldridge

JD Fuchs

M Allen

M Elizaga

M Mulligan

M Pensiero

N Frahm

N Kochar

R Sheets

SA Kalams

Retrovirology

PubMed

Crossref

POSTER PRESENTATION Open AccessFirst-in-human phase I clinical trial of arecombinant vesicular stomatitis virus(rVSV)-based preventive HIV-1 vaccineJD Fuchs1*, I Frank2, N Kochar3, M Elizaga3, M Allen4, D Carter3, N Frahm3, SA Kalams5, M Mulligan6, R Sheets4,M Pensiero4, D Clarke7, J Eldridge7From AIDS Vaccine 2012Boston, MA, USA. 9-12 September 2012BackgroundReplicating viral vectors are promising HIV vaccine can-didates that may enhance immunogenicity through pro-longed antigen expression. VSV is the first replicatingviral vector after vaccinia to be tested clinically as an HIVvaccine; here we present preliminary safety and immuno-genicity data from a phase 1a trial.MethodsHVTN 090 enrolled sixty healthy, HIV-1-uninfectedadults in a randomized, double-blinded, placebo-con-trolled dose escalation study. Groups of 12 participantsreceived rVSV Indiana HIV Gag vaccine at 5 dose levels(4.6 x 103 to 3.4 x 107 PFU) (N=10/group) or placebo(N=2/group), delivered intramuscularly at 0 and 2months. Reactogenicity over 7 days, adverse events(AEs), and viral cultures from whole blood, urine, salivaand swabs of oral lesions were collected. HIV-1-specificCD4+ and CD8+ T-cell responses to Gag peptides weremeasured 1 and 2 weeks post-boost by intracellularcytokine staining.ResultsThe study is ongoing and data are blinded. The medianage was 24; 47% were female and 37% were non-white.Local and systemic reactogenicity was self-limited, mildto moderate in intensity and increased with dose, withheadache reported most commonly (52%). At the highestdose, 92% reported systemic symptoms, including flu-likesyndrome (41%), fever (41%), and moderate chills (33%).Lymphadenopathy, decreased neutrophil count, oralulceration, and presyncope were each seen in > 1 partici-pant. No severe reactogenicity, encephalitis, or product-related SAEs were reported, and all VSV cultures werenegative at all doses tested. Low frequency HIV-specificCD4+ (9%) and CD8+ (3%) T-cell responses weredetected post-boost at the first 3 dose levels.ConclusionImmunization with an attenuated, replicating rVSV Indi-ana HIV-1 vaccine has an acceptable reactogencity andsafety profile to date. Preliminary data reveal few T-cellresponses at lower doses. Immunogenicity of the vaccineat the highest doses and in heterologous prime-boostregimens will guide future vector development.Author details1San Francisco Dept. of Public Health, San Francisco, CA, USA. 2University ofPennsylvania, USA. 3Fred Hutchinson Cancer Center, USA. 4Division of AIDS,NIH, USA. 5Vanderbilt University, USA. 6Emory University, USA. 7ProfectusBiosciences, USA.Published: 13 September 2012doi:10.1186/1742-4690-9-S2-P134Cite this article as: Fuchs et al.: First-in-human phase I clinical trial of arecombinant vesicular stomatitis virus (rVSV)-based preventive HIV-1vaccine. Retrovirology 2012 9(Suppl 2):P134.1San Francisco Dept. of Public Health, San Francisco, CA, USAFull list of author information is available at the end of the articleFuchs et al. Retrovirology 2012, 9(Suppl 2):P134http://www.retrovirology.com/content/9/S2/P134© 2012 Fuchs et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.

First-in-human phase I clinical trial of a recombinant vesicular stomatitis virus (rVSV)-based preventive HIV-1 vaccine

http://dx.doi.org/10.1186/1742-4690-9-S2-P134

First-in-human phase I clinical trial of a recombinant vesicular stomatitis virus (rVSV)-based preventive HIV-1 vaccine

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