11th International AIDS Conference Vancouver, British Columbia — July 7-12, 1996

Int Conf AIDS 1996 Jul 7-12; 11:24 (abstract no. LB.A.6013)
De Giuli MC, Gimelli M, Ghioni C, Radaelli A, Teeuwsen V, van Gils M, den Haaft P, Borgers W, Heeney JL; University of Milan, Milan, Italy. Fax: 0039-2-7014637. E-mail: degiuli@imiucca.csi.unimi.it.

OBJECTIVE: To analyze the immune response of Rhesus macaques immunized with live, non replicating, recombinant Fowlpoxvirus carrying the complete HIV-1(SF2) env gene, and to verify its protective ability.

METHODS: On the genetic background of Fowlpoxvirus, a live, recombinant vector containing the HIV-1(SF2) env gene has been generated. In this construct, characterized by an abortive replicative cycle in non-avian species, the env gene has been inserted deleted of the nef gene; a mutagenesis has also been performed to modify the T5CT sequence to avoid a premature termination of the transcription. The recombinant and its not engineered wild-type counterpart have been utilized to immunize two groups of macaques by a primary intramuscular injection with 10(7) PFU/animal and two boosters with 10(7) and 10(8) PFU/animal. Their env-specific humoral and cellular immunity being characterized in detail. One month after the third immunization all animals were challenged by intravenous inoculation of in vivo titered SHIV(SF13) chimeric virus.

RESULTS: After the second booster, env-specific humoral immunity was demonstrated by ELISA and Western Blot. Antibody titers and neutralization activities were present only in Fowlpox/env immunized animals, while cell-mediated immunity was undetectable by CTL or lymphoproliferation assays. One month after challenge all macaques were found infected by PCR; however, two weeks post infection, the viral burden was more than 3-fold higher in control than vaccinated animals. Two months later all macaques became virus-negative.

CONCLUSIONS: The results demonstrate that the Fowlpox/env recombinant construct is unable to protect Rhesus monkeys against SHIV infection but can reduce viral burden in immunized animals. A higher dosage and/or a modified protocol including the gag/pol genes may improve its efficacy.

960707
LBA6013

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