AEGiS-13IAC: Various routes of application of new type HIV-1 DNA vaccine induces strong antigen-specific immune responses.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Various routes of application of new type HIV-1 DNA vaccine induces strong antigen-specific immune responses.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. WeOrA481)

Okuda K, Liu L-J, Watabe S, Hamajima K, Wahren B, Xin K-Q
K. Okuda, Yokohama City University, Department of Bacteriology, School of Medicine 3-9 Fukuura Kanazawa-ku, Yokohama 236 0004, Japan, Tel.: +81 45 787 26 02, Fax: +81 45 787 25 09, E-mail: kokuda@med.yokohama-cu.ac.jp

BACKGROUND: Our previous reports (Okada et al. J Immunol 1997; Tsuji et al. Eur J Immunol 1998; Tsuji et al. J Immunol 1998; Sasaki et al. J Virol 1998; Kusakabe et al. J Immunol 2000) revealed that DNA vaccine induces strong levels of cytotoxic T lymphocyte (CTL) response and delayed type of hypersensitivity (DTH) response. In this study, we first examined a new type of HIV-1 DNA vaccine encoded by humanized codons. Then we compared the immunogenicity of a newly synthesized DNA vaccine by various routes of immunization.

METHODS: The immunogenicity of DNA vaccines with humanized codon usage of HIV-1 genes was tested. This new type of DNA vaccine was synthesized and constructed from the HIV-1 V3 region, CD4 binding region and CTL epitopes of the gag-pol region. In addition, the ubiquitin gene in the 5' site of the DNA of the HIV-1 gene was also inserted in this new synthetic DNA vaccine.

RESULTS: Our preliminary results indicated that ubiquitinized DNA vaccine with humanized codon usage showed a higher level of immune response than DNA vaccine which does not contain the ubiquitin gene. Intramuscular immunization induced high levels of Th1 type immune response, whereas intranasal (i.n.) immunization induced high levels of Th2 response. High levels of HIV-1 specific mucosal antibodies were observed when HIV-1 DNA vaccine was administered by the i.n. route. In addition, percutaneous (p.c.) application of DNA vaccine induced high levels of immunity in mice. After removing the hair we removed keratinocytes with adhesive tape. Fifty m g of HIV env DNA vaccine was painted. After painting a couple of times, we observed strong levels of HIV-specific immunity. This method is useful for eliminating side effects of DNA vaccine and provides good compliance to clinical field. Discussion: Our results shows that HIV-1 virus protein encoded by humanized codons and also containing the ubiquitin gene induces high levels of immune response. Immunization by the i.n. route induced high levels of immune response. We also observed the tissue distribution of HIV-1 DNA vaccine for various routes1 of vaccination, and found that i.n. and p.c. immunization caused a wide distribution of DNA plasmids to the immune host.

CONCLUSIONS: A new type of DNA vaccine which encodes both the HIV-1 gene using humanized codons and the ubiquitin gene induce high levels of immune response by various routes of immunization.

Keywords: AEGIS, AIDS Vaccines, Vaccines, DNA, HIV-1, HIV Antigens, HIV Envelope Protein gp160, Immunization, HIV, HIV Infections, T-Lymphocytes, Cytotoxic, HIV Envelope Protein gp120, Adjuvants, Immunologic, HIV Core Protein p24, Vaccination, Plasmids, Antibodies, Animal, Mice, immunology, genetics
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