Design and evaluation of multi-gene, multi-clade HIV-1 MVA vaccines

Vaccine. 2009 Sep 25;27(42):5885-95. doi: 10.1016/j.vaccine.2009.07.039. Epub 2009 Aug 3.

Abstract

Recombinant modified vaccinia virus Ankara (rMVA) expressing HIV-1 genes are promising vaccine candidates. Toward the goal of conducting clinical trials with one or a cocktail of recombinant viruses, four rMVAs expressing env and gag-pol genes from primary HIV-1 isolates representing predominant subtypes from Kenya, Tanzania, Uganda, and Thailand (A, C, D, and CRF01_AE, respectively) were constructed. Efficient expression, processing, and function of Env and Gag were demonstrated. All inserted genes were shown to be genetically stable after repeated passage in cell culture. Strong HIV-specific cellular and humoral immune responses were elicited in mice immunized with each individual vaccine candidate. The MVA/CMDR vaccine candidate expressing CRF01_AE genes has elicited HIV-specific T-cell responses in two independent Phase I clinical trials. Further testing of the other rMVA is warranted.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology*
  • Animals
  • Cells, Cultured
  • HIV Antibodies / immunology
  • HIV Infections / prevention & control*
  • HIV-1 / immunology*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mutagenesis
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocytes / immunology
  • Vaccinia virus / immunology*
  • env Gene Products, Human Immunodeficiency Virus / genetics
  • env Gene Products, Human Immunodeficiency Virus / immunology
  • gag Gene Products, Human Immunodeficiency Virus / genetics
  • gag Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • AIDS Vaccines
  • HIV Antibodies
  • env Gene Products, Human Immunodeficiency Virus
  • gag Gene Products, Human Immunodeficiency Virus