AEGiS-11IAC: Efficacy of a DNA vaccination to induce neutralizing antibody and cytotoxic cells against HIV-1.

11th International AIDS Conference


Vancouver, British Columbia — July 7-12, 1996

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Efficacy of a DNA vaccination to induce neutralizing antibody and cytotoxic cells against HIV-1.

Int Conf AIDS 1996 Jul 7-12; 11:6 (abstract no. Mo.A.150)
Fukushima J, Hamajima K, Asakura Y, Bukawa H, Tsuji T, Xin KQ, Nishioka K, Cullen BR, Okuda K; Yokohama City University School of Medicine, Yokohama, Japan. Fax: 81-45-787-2509. E-mail: jfukusim@med.yokohama-cu.ac.jp.

OBJECTIVE: The efficacy of DNA vaccines for protecting HIV-1 infection was studied by using expression plasmids for Gag, Env, and Rev proteins.

METHODS: We constructed expression vectors for HIV-1 genes driving cytomegalovirus promoter. These expression plasmids were injected with cationic liposomes into mice, rabbits, guinea pigs, and Japanese macaques intramuscularly or intraperitonealy. Antibody titre and cell mediated immunity were monitored by enzyme-linked immunosorbent assay, delayed-type hypersensitivity, or cytotoxic T lymphocyte assays. We also evaluate the virus neutralizing activity of serum antibody by p24 assay using several laboratory strains and clinical isolates.

RESULTS: After three months of intramuscularly immunization, the antibody titre of 1:213 of serum IgG in Japanese macaques was obtained when IIIB-env region expression vector was injected. These antibodies neutralized not only laboratory strains but primary isolates strongly. This immunization was also induced certain level of V3 peptide specific cytotoxic T cells and DTH activity in the mice when small amount of DNA (2 micrograms) was injected. In addition, when Gag region expression vector was used for DNA immunization, we could observe the virus-like particles in the muscle. Humoral and cell-mediated immunity was detected against Gag peptide.

CONCLUSIONS: Direct plasmid injection is a candidate for new-type of vaccination methods against HIV-1. The expression of Gag protein in the muscle may mimic the elicitation of anti-virus immunity of HIV-1 infection. SCID/HU mice or chimpanzee should be used for the protection of HIV-1 infection to evaluate the efficacy of these vaccines.

Keywords: AEGIS, HIV-1, Gene Products, gag, Killer Cells, HIV Infections, Vaccination, Gene Products, rev, T-Lymphocytes, Cytotoxic, Vaccines, DNA, Antibodies, Immunity, Cellular, Plasmids, Genetic Vectors, Animal, Mice, Rabbits, immunology, ICA11KWDaegis,hiv-1,geneproducts,gag,killercells,hivinfections,vaccination,geneproducts,rev,t-lymphocytes,cytotoxic,vaccines,dna,antibodies,immunity,cellular,plasmids,geneticvectors,animal,mice,rabbits,immunology,ica11

960707
MoA150

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