Titre du document / Document title

Head-to-head comparison on the immunogenicity of two HIV/AIDS vaccine candidates based on the attenuated poxvirus strains MVA and NYVAC co-expressing in a single locus the HIV-I_BX08 gp120 and HIV-1_IIIB Gag-Pol-Nef proteins ofclade B

Auteur(s) / Author(s)

GOMEZ Carmen Elena ⁽¹⁾ ; NAJERA Jose Luis ⁽¹⁾ ; PEREZ JIMENEZ Eva ⁽¹⁾ ; JIMENEZ Victoria ⁽¹⁾ ; WAGNER Ralf ⁽²⁾ ; GRAF Marcus ⁽³⁾ ; FRACHETTE Marie-Joelle ⁽⁴⁾ ; LILJESTRÖM Peter ⁽⁵⁾ ; PANTALEO Giuseppe ⁽⁶⁾ ; ESTEBAN Mariano ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, CSIC, Ciudad Universitaria Cantoblanco, 28049 Madrid, ESPAGNE
⁽²⁾ Institute of Medical Microbiology and Hygiene, University of Regensburg, ALLEMAGNE
⁽³⁾ Geneart GmbH, Josef-Engert-Str. 11, 93053 Regensburg, ALLEMAGNE
⁽⁴⁾ Sanofi Pasteur, 1541 Avenue Marcel Merieux, 69280 Marcy Létoile, FRANCE
⁽⁵⁾ Microbiology and Tumorbiology Centre, Karolinska Institut, Stockholm, SUEDE
⁽⁶⁾ Laboratory of AIDS Immunopathogenesis, Departmen of Medicine, Centre Hospitalier Universitaire Vaudois, Av. De Beaumont 29-Hopital Beaumont, 1011 Lausanne, SUISSE

Résumé / Abstract

In this investigation we have generated and defined the immunogenicity of two novel HIV/AIDS vaccine candidates based on the highly attenuated vaccinia virus strains, MVA and NYVAC, efficiently expressing in the same locus (TK) and under the same viral promoter the codon optimized HIV-1 genes encoding gp120 and Gag-Pol-Nef antigens ofclade B (referred as MVA-B and NYVAC-B). In infected human HeLa cells, gp120 is released from cells and GPN is produced as a polyprotein; NYVAC-B induces severe apoptosis but not MVA-B. The two poxvirus vectors showed genetic stability of the inserts. In BALB/c and in transgenic HHD mice for human HLA-A2 class I, both vectors are efficient immunogens and induced broad cellular immune responses against peptides represented in the four HIV-1 antigens. Some differences were observed in the magnitude and breadth of the immune response in the mouse models. In DNA prime/poxvirus boost protocols, the strongest immune response, as measured by fresh IFN-γ and IL-2 ELISPOT, was obtained in BALB/c mice boosted with NYVAC-B, while in HHD mice there were no differences between the poxvirus vectors. When the prime/boost was performed with homologous or with combination of poxvirus vectors, the protocols MVA-B/MVA-B and NYVAC-B/NYVAC-B, or the combination NYVAC-B/MVA-B gave the most consistent broader immune response in both mouse models, although the magnitude of the overall response was higher for the DNA-B/poxvirus-B regime. All of the immunization protocols induced some humoral response against the gpl60 protein from HIV-1 clone LAV. Our findings indicate that MVA-B and NYVAC-B meet the criteria to be potentially useful vaccine candidates against HIV/AIDS.

Revue / Journal Title

Vaccine   ISSN 0264-410X   CODEN VACCDE 

Source / Source

2007, vol. 25, n^o15, pp. 2863-2885 [23 page(s) (article)] (46 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Oxford, ROYAUME-UNI  (1983) (Revue)

Mots-clés anglais / English Keywords

Immunopathology ; Infection ; Viral disease ; Immune deficiency ; Virus ; Retroviridae ; Lentivirus ; AIDS ; Animal model ; Immune response ; Vector ; Protein ; Attenuated strain ; Vaccine ; Immunogenicity ; Poxviridae ; Human immunodeficiency virus ;

Mots-clés français / French Keywords

Immunopathologie ; Infection ; Virose ; Immunodéficit ; Virus ; Retroviridae ; Lentivirus ; SIDA ; Modèle animal ; Réponse immune ; Vecteur ; Protéine ; Souche atténuée ; Vaccin ; Immunogénicité ; Poxviridae ; Virus immunodéficience humaine ;

Mots-clés espagnols / Spanish Keywords

Inmunopatología ; Infección ; Virosis ; Inmunodeficiencia ; Virus ; Retroviridae ; Lentivirus ; SIDA ; Modelo animal ; Respuesta inmune ; Vector ; Proteína ; Cepa atenuada ; Vacuna ; Inmunogenicidad ; Poxviridae ; Human immunodeficiency virus ;

Mots-clés d'auteur / Author Keywords

HIV/AIDS ; Clade B vaccine ; Poxvirus vectors ; MVA ; NYVAC ; Immune response ; Mouse models ;

Localisation / Location

INIST-CNRS, Cote INIST : 20289, 35400014562699.0150