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A canarypox-based (ALVAC) recombinant expressing the rabies G glycoprotein has been utilized to assess in vitro and in vivo biological properties of the canarypox virus vector system. In vitro studies have shown that no replication of the virus can be detected on six human-derived cell lines, nor can the virus be readily adapted to replicate on non-avian cells. Expression of the rabies G can be detected on all cell lines analyzed in the absence of productive viral replication. Analysis of viral-specific DNA accumulation indicated that the block in the replication cycle in the human cell lines analyzed occurred prior to DNA replication. The exact nature of the block, however, remains unknown. The concept of using a non-replicating immunization vehicle has been demonstrated through extensive in vivo studies in a range of species including non-human primates and humans. The results of such in vivo studies have exemplified the safety and immunogenicity of the ALVAC vaccine vector.

This paper presents data derived from safety and efficacy studies of ALVAC-based rabies and feline leukemia virus (FeLV) vaccine candidates in target species. Inoculation of the ALVAC-RG recombinant was well tolerated in all species including humans and very young dogs. Protection induced in dogs against rabies challenge was long-lasting and could be elicited in the face of high levels of maternally-derived neutralizing antibody. Parenteral inoculation of cats with an ALVAC-FeLV recombinant was safe and induced protection against persistent infection following oro-nasal FeLV challenge.

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.

The equine herpesvirus 1 glycoprotein 14 (EHV-1 gp14) gene was cloned, sequenced, and expressed by vaccinia virus recombinants. Recombinant virus vP613 elicited the production of EHV-1-neutralizing antibodies in guinea pigs and was effective in protecting hamsters from subsequent lethal EHV-1 challenge. Coexpression of EHV-1 gp14 in vaccinia virus recombinant vP634 along with EHV-1 gp13 (P. Guo, S. Goebel, S. Davis, M. E. Perkus, B. Languet, P. Desmettre, G. Allen, and E. Paoletti, J. Virol. 63:4189-4198, 1989) greatly enhanced the protective efficacy in the hamster challenge model over that obtained with single recombinants. The inoculum doses (log10) required for protection of 50% of hamsters were 6.1 (EHV-1 gp13), 5.2 (EHV-1 gp14), and less than 3.6 (vaccinia virus recombinant expressing both EHV-1 glycoproteins [gp13 and gp14]).

The vaccination of wild animals against rabies has been developed most extensively in Europe. Experiments have demonstrated the efficacy of a vaccinia-rabies recombinant virus administered by the oral route in foxes. The innocuity of this vaccine was tested in the target species as well as in several non-target wild and domestic species. Because of its safety and heat-stability, this recombinant virus should offer an excellent alternative to the attenuated strains of rabies virus currently used in the field. A large scale field trial was conducted in Belgium in October 1988 to assess the efficacy of this new vaccine-bait systems.

A freeze-dried vaccine against Rinderpest was prepared from modified virus multiplied in calf kidney cell culture. Characteristics of the vaccine are as follows: high titre after freeze-drying (10(4) CCID50/dose), well-adapted freeze-drying stabilizer which ensures maintenance of the infective titre of the vaccinal virus, even under severe conditions (3.5 days at +45 degrees C), use of an appropriate solvent: magnesium sulphate molar solution or more simply physiological saline (for stability after reconstitution even at high temperatures--up to 4 h at +45 degrees C). The activity of the vaccine, tested in cattle by antibody titration and resistance to specific challenge perfectly satisfies requirements set by the WHO and OIE.

A field trial of fox vaccination against rabies using a vaccinia-rabies recombinant virus was carried out in Belgium on October 24, 1987. Each vaccine capsule contained a suspension of 10(8) TCID50 of the recombinant virus and was introduced into a chicken head. Each chicken head contained 150 mg of tetracycline as a marker of uptake. Two hundred and fifty heads were distributed in an area of 6 km2 situated within a military zone. The bait uptake was monitored for 15 days after the distribution. Sixty-three per cent of the chicken heads were taken by wild animals within that period. The trial was controlled according to the rules defined by the World Health Organisation.