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Journal of Virology, January 2004, p. 146-157, Vol. 78, No. 1
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.1.146-157.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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

Clarisse Lorin,1 Lucile Mollet,1 Frédéric Delebecque,1 Chantal Combredet,1 Bruno Hurtrel,2 Pierre Charneau,3 Michel Brahic,1 and Frédéric Tangy1*

Unité des Virus Lents, CNRS URA 1930,1 Unité de Physiopathologie des Infections Lentivirales,2 Groupe de Virologie Moléculaire et de Vectorologie, Institut Pasteur, Paris, France3

Received 5 May 2003/ Accepted 19 September 2003

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.

* Corresponding author. Mailing address: Unité des Virus Lents, Institut Pasteur, 28 rue du Dr Roux, 75015 Paris, France. Phone: (33) 1-45-68-87-73. Fax: (33) 1-40-61-31-67. E-mail: ftangy{at}pasteur.fr.

Journal of Virology, January 2004, p. 146-157, Vol. 78, No. 1
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.1.146-157.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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