A recombinant live attenuated measles vaccine vector primes effective HLA-A0201-restricted cytotoxic T lymphocytes and broadly neutralizing antibodies against HIV-1 conserved epitopes.
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.
Lorin
Clarisse
C
Unité des Virus Lents, CNRS URA 1930, Institut Pasteur, 28 rue du Dr Roux, Paris 75015, France.
Delebecque
Frédéric
F
Labrousse
Valérie
V
Da Silva
Lucie
L
Lemonnier
François
F
Brahic
Michel
M
Tangy
Frédéric
F
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018791:CD4 Lymphocyte Count; D000939:Epitopes; D015686:Gene Products, env / Q000276:immunology; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000097:blood*; D015497:HIV-1 / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D007114:Immunization; D016898:Interferon-alpha / Q000032:analysis; D008458:Measles Vaccine / Q000235:genetics / Q000276:immunology*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D015703:Antigens, CD; D000939:Epitopes; D015686:Gene Products, env; D015483:HIV Antibodies; D015234:HLA-A Antigens; D016898:Interferon-alpha; C497859:Mcp protein, mouse; D008458:Measles Vaccine; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1