Cross-clade protection induced by human immunodeficiency virus-1 DNA immunogens expressing consensus sequences of multiple genes and epitopes from subtypes A, B, C, and FGH.
The correlate of protection in human immunodeficiency virus (HIV) infection is not known, but preclinical and clinical studies support the involvement of both antibodies and cellular immunity. In addition, the existence of multiple HIV clades makes HIV vaccine design especially challenging. We have constructed a vaccine platform with an HIV-1 subtype B DNA immunogen expressing full length consensus sequences from HIV-1 rev, nef, tat, and gag with additional cellular epitope clusters from the env and pol regions. Furthermore, this platform has been extended to three additional plasmids expressing the same immunogens but originating from subtypes A or C consensus or FGH ancestral sequences. Immunogenicity in BALB/c mice, by gene gun or intramuscular delivery, revealed strong IFN-gamma production in response to in vitro re-stimulation with a H-2d restricted gag peptide (AMQMLKETI) or even stronger toward an env epitope (RGPGRAFVTI). Weak humoral immunity was detected. Gene gun immunization with a cocktail of all four plasmids induced pre-challenge cellular immunity in C57Bl6/A2.01 mice and subsequently a robust frequency of protection (11/12 animals) after experimental challenge with subtype A or B HIV-1/Murine Leukemia Virus (HIV-1/MuLV). The cross-clade protection observed in this challenge experiment demonstrates that these multigene/multiepitope HIV DNA immunogens are likely to be potent immunogens also against the HIV-infection of human beings.
Malm
Maria
M
FIT Biotech Plc, Tampere, Finland.
Rollman
Erik
E
Ustav
Mart
M
Hinkula
Jorma
J
Krohn
Kai
K
Wahren
Britta
B
Blazevic
Vesna
V
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D016384:Consensus Sequence; D004195:Disease Models, Animal; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D015693:Gene Products, nef / Q000235:genetics / Q000276:immunology; D015684:Gene Products, pol / Q000235:genetics / Q000276:immunology; D015694:Gene Products, rev / Q000235:genetics / Q000276:immunology; D015696:Gene Products, tat / Q000235:genetics / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus; D054302:pol Gene Products, Human Immunodeficiency Virus; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D000939:Epitopes; D015683:Gene Products, gag; D015693:Gene Products, nef; D015684:Gene Products, pol; D015694:Gene Products, rev; D015696:Gene Products, tat; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; C060467:HIV pol protein p65; D019444:Vaccines, DNA; D054311:nef Gene Products, Human Immunodeficiency Virus; D054302:pol Gene Products, Human Immunodeficiency Virus; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma