Philippe Desmettre

Efficacy studies on a canarypox-rabies recombinant virus.

Recombinant avipox viruses have been developed expressing the rabies glycoprotein gene. A fowlpox-rabies recombinant has previously been shown to be protective against live rabies virus challenge in a number of non-avian species. This report describes the development of a canarypox-rabies recombinant. A comparison is made of the protective efficacy of this recombinant with other pox-rabies recombinants.

Experimental rabies infection and oral vaccination in vampire bats (Desmodus rotundus)

A rabies virus variant isolated from a vampire bat (Desmodus rotundus) and characterized by genome sequencing was used for the standardization of an experimental infection in this species. The parenteral administration of 10(6) MICLD50 of this variant was capable of inducing death from rabies in 89% of animals. The mean duration of post-challenge survival was 12 days. None of the experimental rabid vampire bats showed aggressive behaviour. A vaccinia-rabies glycoprotein recombinant virus vaccine was administered orally to vampire bats on days -120, -90, -30 or -18 pre-challenge, on the same day of challenge, or on day +5 post-challenge. A significant protection was noticed only in animals vaccinated on days -18 or -30 pre-challenge. A longer period of incubation was observed in animals vaccinated 5 days post-challenge.

Protection of chickens with a recombinant fowlpox virus expressing the newcastle disease virus hemagglutinin-neuraminidase gene

A recombinant fowlpox virus expressing the hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) strain Texas was generated. Immunoprecipitation with chicken anti-NDV serum confirmed authentic expression of the HN protein. Protection of chickens from infection with NDV was observed when birds were immunized with the recombinant HN fowlpox virus by the intramuscular route after one or two inoculations. Vaccination by the ocular route with a mixture of fowlpox recombinants expressing the fusion and HN proteins did not show added protection over that seen with the individual viruses.

Recombinant vaccinia virus expression of the bovine leukaemia virus envelope gene and protection of immunized sheep against infection

The bovine leukaemia virus (BLV) envelope gene encoding extracellular glycoprotein gp51 and transmembrane glycoprotein gp30 was cloned into the HA locus of vaccinia virus (Copenhagen strain), downstream of the vaccinia virus early-late promoter, H6, or a triple promoter element consisting of the promoter for the vaccinia virus H6 gene, the promoter for the cowpox virus A-type inclusion (ATI) gene and the promoter for the vaccinia virus HA gene. Inoculation of rabbits or sheep with the recombinant vaccinia virus coding for gp51 and gp30 or an uncleaved env precursor induced neutralizing antibodies to BLV. These antibodies competed with monoclonal antibodies directed against gp51 epitopes F, G, and H previously shown to be of crucial importance for BLV infection. Seven out of eight sheep vaccinated with the vaccinia recombinants resisted a drastic challenge (1.5 x 10(3) sheep infectious doses) with BLV-infected lymphocytes. These results show that vaccination with BLV env vaccinia recombinants protects sheep against infection with extremely high doses of BLV-infected heterologous lymphocytes.

Newcastle disease virus (NDV) vaccine based on immunization with avian cells expressing the NDV hemagglutinin-beuraminidase glycoprotein

Newcastle disease virus (NDV) is a paramyxovirus that bears two envelope glycoproteins at the virion surface. These proteins, fusion and hemagglutinin-neuraminidase (HN), are involved in the immune response against NDV infection. Recombinant cells constitutively expressing at their surface the HN protein from the velogenic Texas strain were generated by introducing the HN gene with a helper-free AEV-based vector. These recombinant cells were used to immunize chickens by various protocols, and birds were subsequently challenged with a lethal NDV injection. Both NDV protection and serologic response were observed.

Vaccines against Rabies Virus

Rabies is one of the oldest recognized diseases. It most probably originated on the African continent and diffusion in North Africa was followed by the spread throughout Europe and Asia. The disease subsequently appeared on the North American continent possibly by transmission through circumpolar animals such as foxes and wolves, though the importation of rabid dogs from Europe is also probable. Today rabies is a disease of major importance, present on all five continents (59,111).