Local immunotherapy of spontaneous feline fibrosarcomas using recombinant poxviruses expressing interleukin 2 (IL2).

We tested the canarypox virus vector ALVAC and the genetically attenuated vaccinia virus vector NYVAC as vehicles for achieving local immunomodulation in domestic animals bearing spontaneous tumours. Following intratumoral administration of ALVAC-, or NYVAC-luciferase in dogs with melanoma, it was demonstrated that viral recombinants remained localized along the needle track, with no virus detectable in the periphery of the tumour. Given these distribution characteristics and their well-documented safety profile, ALVAC- or NYVAC-based recombinants expressing feline or human IL2, respectively, were administered to domestic cats, in order to prevent the recurrence of spontaneous fibrosarcomas. In the absence of immunotherapy, tumour recurrence was observed in 61% of animals within a 12-month follow-up period after treatment with surgery and iridium-based radiotherapy. In contrast, only 39 and 28% of cats receiving either NYVAC-human IL2 or ALVAC-feline IL2, respectively, exhibited tumour recurrences. Based on such results, and in the context of ongoing clinical studies conducted in humans, we discuss the utilization of ALVAC- or NYVAC-based recombinants as viable therapeutic modalities for local immunotherapy or therapeutic vaccination against cancer, both in humans and companion animals.

Modulation of the antibody response to the HIV envelope subunit by co-administration of infectious or heat-inactivated canarypoxvirus (ALVAC) preparations.

Poxviruses are large DNA viruses capable of infecting a broad range of animal species. Infection is generally accompanied by an inflammatory response in the host, the extent of which varies considerably with the specific poxvirus and host species. Regarding ALVAC, a poxvirus derived from the canarypox vaccine strain, Kanapox, and which represents a promising immunization vehicle in humans, nothing is known about its inflammatory capacity. The present study was aimed at documenting this issue in rodents, including mice and guinea pigs. It was then attempted to evaluate how such properties could influence the immunogenicity of an antigen concomitantly administered with ALVAC preparations using the HIV envelope subunit, rgp160, as the model immunogen. The results revealed that ALVAC, either infectious or heat-inactivated, induced in both animal species an early inflammatory response, as evidenced by a rapid migration of neutrophils to the site of inoculation. In parallel, the canarypoxvirus was shown to strongly adjuvant the co-administered immunogen, resulting in a marked increase in Env-specific IgG, IgG1 and particularly IgG2(a) serum titers. Of further interest, the heat-inactivated preparation of ALVAC retained this immunostimulatory activity. Whether or not a link between the inflammatory and immunomodulatory properties of ALVAC exists remains to be established, but such features are clearly interesting with respect to the potential use of ALVAC as an immunization vehicle.

Immunization of experimental animals with reconstituted glycoprotein mixtures of herpes simplex virus 1 and 2: protection against challenge with virulent virus.

Artificial mixtures of the glycoproteins B, C, D, and E of herpes simplex virus 1 and 2 (HSV-1 and HSV-2), purified individually from infected Vero cell lysates by immunoaffinity to monoclonal antibodies, were bound to an aluminum hydroxide gel and were used to immunize mice, guinea pigs, and owl monkeys (Aotus trivirgatus) once or twice (mice and guinea pigs) to as many as four times (owl monkeys). In all animals tested, low levels of neutralizing antibodies were detected only after two or more immunizations. Lymphocyte transformation tests in owl monkeys suggested low or borderline levels of cellular immunity. The survival of immunized mice after intracerebral challenge was inversely related to the challenge dose. Immunized guinea pigs challenged by intravaginal inoculation showed reduced morbidity at the site of inoculation and were protected from CNS disease. Both immunized and nonimmunized monkeys were highly susceptible and could not be differentiated with respect to morbidity or mortality when challenged with 1,000 pfu of HSV-2 by the intravaginal route.