Prime-Boost Immunization of Codon Optimized HIV-1 CRF01_AE Gag in BCG with Recombinant Vaccinia Virus Elicits MHC Class I and II Immune Responses in Mice

• Published in: Immunological investigations 2009-11, Vol.38 (8), p.762-779
• Main Authors: Promkhatkaew, Duanthanorm, Pinyosukhee, Nadthanan, Thongdeejaroen, Wilai, Teeka, Jantima, Wutthinantiwong, Preeda, Leangaramgul, Preecha, Sawanpanyalert, Pathom, Warachit, Paijit
• Format: Article
• Language: English
• Subjects: AIDS Vaccines; Animals; BCG; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - pathology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; Codon - genetics; Codon usage; Cytotoxicity, Immunologic; gag Gene Products, Human Immunodeficiency Virus - genetics; gag Gene Products, Human Immunodeficiency Virus - immunology; gag Gene Products, Human Immunodeficiency Virus - metabolism; Genetic Engineering; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class I - metabolism; Histocompatibility Antigens Class II - immunology; Histocompatibility Antigens Class II - metabolism; HIV Infections - immunology; HIV Infections - prevention & control; HIV vaccine; HIV-1 - genetics; HIV-1 - immunology; Immunization, Secondary; Interferon-gamma - biosynthesis; Interleukin-2 - biosynthesis; Mice; Mice, Inbred BALB C; Mycobacterium bovis - immunology; Prime-boost immunization; Vaccines, Synthetic; Vaccinia - genetics; Vaccinia - immunology; Vaccinia virus
• ISSN: 0882-0139; 1532-4311
• DOI: 10.3109/08820130903070544

The HIV-1 CRF01_AE gag gene was modified by codon restriction for Mycobacterium spp. and transformed into BCG; and it was designated as rBCG codon optimized gagE. This produced 11 fold higher HIV-1 gag protein expression than the recombinant native gene rBCG HIV-1gagE. In mice, CTL activity could be induced either by a single immunization of the codon optimized construct or by using it as a priming antigen in the prime-boost modality with recombinant Vaccinia virus expressing native HIV-1 gag. Specific secreted cytokine responses were also investigated. Only when rBCG gag was codon optimized did the prime-boost immunization produce significantly enhanced IFN-γ and IL-2 secretion indicating recognition via CD4+ and CD8+ T cells, and these responses seemed to be codon optimized immunogen dose-responsive. On contrary, the prime-boost vaccination using an equal amount of native rBCG HIV-1gagE instead, or a single rBCG codon optimized gagE immunization, had no similar effect on the cytokine secretion. These findings suggest that the use of recombinant codon BCG construct with recombinant Vaccinia virus encoding CRF01_AE gag as the prime-boost HIV vaccine candidate, will induce CD4+ Th1 and CD8+ T cell cytokine secretions in addition to enhancing CD8+ CTL response.