DNA and modified vaccinia virus Ankara vaccines encoding multiple cytotoxic and helper T-lymphocyte epitopes of human immunodeficiency virus type 1 (HIV-1) are safe but weakly immunogenic in HIV-1-uninfected, vaccinia virus-naive adults.

Publication Type:

Journal Article

Source:

Clinical and vaccine immunology : CVI, Volume 19, Issue 5, p.649-58 (2012)

Keywords:

2012, Adolescent, Adult, AIDS Vaccines, Double-Blind Method, Epitopes, T-Lymphocyte, Female, Genetic Vectors, HIV-1, Humans, interferon-gamma, Interleukin-2, Male, Perforin, Placebos, September 2012, T-Lymphocytes, Tumor Necrosis Factor-alpha, Vaccine and Infectious Disease Division, Vaccines, DNA, VACCINIA VIRUS, Viral Vaccines, Young Adult

Abstract:

We evaluated a DNA plasmid-vectored vaccine and a recombinant modified vaccinia virus Ankara vaccine (MVA-mBN32), each encoding cytotoxic and helper T-lymphocyte epitopes of human immunodeficiency virus type 1 (HIV-1) in a randomized, double-blinded, placebo-controlled trial in 36 HIV-1-uninfected adults using a heterologous prime-boost schedule. HIV-1-specific cellular immune responses, measured as interleukin-2 and/or gamma interferon production, were induced in 1 (4%) of 28 subjects after the first MVA-mBN32 immunization and in 3 (12%) of 25 subjects after the second MVA-mBN32 immunization. Among these responders, polyfunctional T-cell responses, including the production of tumor necrosis factor alpha and perforin, were detected. Vaccinia virus-specific antibodies were induced to the MVA vector in 27 (93%) of 29 and 26 (93%) of 28 subjects after the first and second immunizations with MVA-mBN32. These peptide-based vaccines were safe but were ineffective at inducing HIV-1-specific immune responses and induced much weaker responses than MVA vaccines expressing the entire open reading frames of HIV-1 proteins.