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.
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-gamma 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.
Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi, Thailand. duanthanorm.p@dmsc.mail.go.th
Duanthanorm
D
Promkhatkaew
Nadthanan
N
Pinyosukhee
Wilai
W
Thongdeejaroen
Jantima
J
Teeka
Preeda
P
Wutthinantiwong
Preecha
P
Leangaramgul
Pathom
P
Sawanpanyalert
Paijit
P
Warachit
D016915:AIDS Vaccines; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D003062:Codon / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D005818:Genetic Engineering; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000276:immunology; D014614:Vaccines, Synthetic; D014615:Vaccinia / Q000235:genetics / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D016915:AIDS Vaccines; D003062:Codon; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D014614:Vaccines, Synthetic; D054301:gag Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma