A recombinant live attenuated measles vaccine vector primes effective HLA-A0201-restricted cytotoxic T lymphocytes and broadly neutralizing antibodies against HIV-1 conserved epitopes

Vaccine. 2005 Aug 22;23(36):4463-72. doi: 10.1016/j.vaccine.2005.04.024.

Abstract

Live attenuated measles vaccine (MV) could provide a safe and efficient pediatric vaccination vector to immunize children simultaneously against measles and human immunodeficiency virus type 1 (HIV-1). To evaluate the capacity of a vector derived from the certified Schwarz measles vaccine (MVSchw) to prime effective cytotoxic T cells (CTL) and broad neutralizing antibodies against HIV-1 conserved epitopes, we generated recombinant MVSchw viruses expressing HIV-1 antigens. We demonstrate that a recombinant MVSchw virus expressing an HIV-1-derived CTL polyepitope primes effective HLA-A0201-restricted CTLs against multiple conserved HIV-1 epitopes in mice susceptible to measles and humanized for the major histocompatibility complex (MHC) class-I molecule HLA-A0201. Additionally, we show that a recombinant MVSchw virus expressing an HIV-1(89.6) gp140 glycoprotein whose hyper variable V1, V2 and V3 loops were deleted (DeltaV1V2V3gp140), induces broadly neutralizing antibodies against HIV-1 primary isolates. These results show that the MVSchw pediatric vaccination vector induces efficient cellular and humoral HIV-specific immune responses.

Publication types

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

MeSH terms

  • AIDS Vaccines / immunology*
  • Animals
  • Antigens, CD / analysis
  • CD4 Lymphocyte Count
  • Epitopes
  • Gene Products, env / immunology
  • Genetic Vectors
  • HIV Antibodies / blood*
  • HIV-1 / immunology*
  • HLA-A Antigens / immunology*
  • Immunization
  • Interferon-alpha / analysis
  • Measles Vaccine / genetics
  • Measles Vaccine / immunology*
  • Membrane Cofactor Protein
  • Membrane Glycoproteins / analysis
  • Mice
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccines, Attenuated / immunology
  • Vaccines, Synthetic / immunology*
  • env Gene Products, Human Immunodeficiency Virus

Substances

  • AIDS Vaccines
  • Antigens, CD
  • Epitopes
  • Gene Products, env
  • HIV Antibodies
  • HLA-A Antigens
  • Interferon-alpha
  • Mcp protein, mouse
  • Measles Vaccine
  • Membrane Cofactor Protein
  • Membrane Glycoproteins
  • Vaccines, Attenuated
  • Vaccines, Synthetic
  • env Gene Products, Human Immunodeficiency Virus
  • gp140 envelope protein, Human immunodeficiency virus 1