AEGiS-13IAC: Adeno-associated Virus Vector-Based Vaccine Induces Long-term Humoral and Cell-Mediated Immunity against Human Immunodeficiency Virus.

13th International AIDS Conference

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

Adeno-associated Virus Vector-Based Vaccine Induces Long-term Humoral and Cell-Mediated Immunity against Human Immunodeficiency Virus.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. TuOrA289)

Xin K, Urabe M, Yang J, Hamajima K, Monahan J, Okuda K, Ozawa K, Okuda K
KE-QINXin, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan, Tel.: 81-45-787-2602, Fax: 81-45-787-2509, E-mail: kqxin@med.yokohama-cu.ac.jp

BACKGROUND: Adeno-associated virus (AAV) vector has been widely used for gene therapy in a variety of preclinical studies. The virus has infected most of the population and never shown any pathogenic effects in humans. AAV vector which can integrate into the cellular DNA has been shown to confer long-term gene expression in a number of tissues. In this study, the immunogenicity of the vector containing HIV envelope gene (AAV-HIVenv) was examined in animal models.

METHODS: The AAV vectors expressing HIV env (AAV-HIVenv) and murine IL-2 (AAV-IL2) were constructed by the calcium phosphate coprecipitation method. AAV-HIVenv vecotr (106-1011 particles) with or without AAV-IL2 vector (1010 particles) was intramuscularly injected once into BALB/c mice. AAV-HIVenv vector (5x108-5x1013 particles) was intramuscularly injected into Japanese macaque monkeys on day 0 and 30

RESULTS: A single injection of 1010 particles of AAV-HIVenv vector induced strong HIV-1-specific serum IgG (log214), fecal IgA (log212) antibodies and cell-mediated immunity (CMI) including cytotoxic T lymphocyte activity (25% specific cell lysis at E/T ratio of 80) and delayed-type hypersensitivity (DTH) response (13.6x10-2 mm) in BALB/c mice. These titers have been stable for ten months. Moreover, co-administration of AAV-HIVenv vector with AAV-IL2 vector significantly enhanced HIV-1-specific CMI. Boosting with AAV-HIVenv vector in the 10th month after immunization strongly enhanced the humoral and CMI responses. Furthermore, the mouse antisera could strongly inhibit the replication of HIV-1 subtype B strains (32%-58%). The injection of AAV-HIVenv vector into Japanese macaque monkeys also induced high levels of humoral immunity and fairly high levels of CTL responses.

CONCLUSIONS: These results demonstrate that AAV vector is useful for HIV vaccine development.

Keywords: AEGIS, Dependovirus, HIV, Immunity, Cellular, AIDS Vaccines, HIV-1, HIV Antibodies, Antibody Formation, Gene Therapy, HIV Antigens, T-Lymphocytes, Cytotoxic, HIV Envelope Protein gp120, Greece, Human, Animal, Mice, immunology
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