A single injection of recombinant measles virus vaccines expressing human immunodeficiency virus (HIV) type 1 clade B envelope glycoproteins induces neutralizing antibodies and cellular immune responses to HIV.
The anchored and secreted forms of the human immunodeficiency virus type 1 (HIV-1) 89.6 envelope glycoprotein, either complete or after deletion of the V3 loop, were expressed in a cloned attenuated measles virus (MV) vector. The recombinant viruses grew as efficiently as the parental virus and expressed high levels of the HIV protein. Expression was stable during serial passages. The immunogenicity of these recombinant vectors was tested in mice susceptible to MV and in macaques. High titers of antibodies to both MV and HIV-Env were obtained after a single injection in susceptible mice. These antibodies neutralized homologous SHIV89.6p virus, as well as several heterologous HIV-1 primary isolates. A gp160 mutant in which the V3 loop was deleted induced antibodies that neutralized heterologous viruses more efficiently than antibodies induced by the native envelope protein. A high level of CD8+ and CD4+ cells specific for HIV gp120 was also detected in MV-susceptible mice. Furthermore, recombinant MV was able to raise immune responses against HIV in mice and macaques with a preexisting anti-MV immunity. Therefore, recombinant MV vaccines inducing anti-HIV neutralizing antibodies and specific T lymphocytes responses deserve to be tested as a candidate AIDS vaccine.
Lorin
Clarisse
C
Unité des Virus Lents, CNRS URA 1930, Institut Pasteur, Paris, France.
Mollet
Lucile
L
Delebecque
Frédéric
F
Combredet
Chantal
C
Hurtrel
Bruno
B
Charneau
Pierre
P
Brahic
Michel
M
Tangy
Frédéric
F
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D000818:Animals; D003429:Cross Reactions; D015686:Gene Products, env / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood*; D015658:HIV Infections / Q000517:prevention & control / Q000821:virology; D006801:Humans; D007114:Immunization; D008251:Macaca; D008459:Measles virus / Q000235:genetics* / Q000276:immunology; D051379:Mice; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000276:immunology
D016915:AIDS Vaccines; D015686:Gene Products, env; D015483:HIV Antibodies; D014614:Vaccines, Synthetic