Fowlpox

Abstract: The coding sequences of VP 2 from a virulent strain, 52/70, of infectious bursal disease virus (IBDV) were excised from a cDNA clone and inserted into a fowlpox plasmid insertion vector. The resulting plasmid, pIBD 1, was used to construct a recombinant fowlpox virus, fpIBD 1, which expressed VP 2 as a β-galactosidase fusion protein. Chickens vaccinated with fpIBD 1 at 1 and 14 days of age, were challenged at 28 days with either IBDV strain 52/70 or the highly virulent strain CS 89. These chickens were protected against mortality, but not against damage to the bursa of Fabricius. The protection achieved by the use of fpIBD 1 shows that VP 2 is a host protective antigen.

Abstract: The avian influenza (AI) vaccine designated TROVAC-AIV H5 (TROVAC-H5) contains a live recombinant fowlpox rec. (FP) recombinant (recFP), expressing the hemagglutinin (HA) gene of an AI H5 subtype isolate. This recombinant vaccine was granted a license in the United States for emergency use in 1998 and full registration in Mexico, Guatemala, and El Salvador where over 2 billion doses have been administered. One injection of TROVAC-H5 protects chickens against AI-induced mortality and morbidity for at least 20 weeks, and significantly decreases shedding after challenge with a wide panel of H5-subtype AI strains, regardless of neuraminidase subtype. Recently, excellent protection was demonstrated against 2003 and 2004 Asian highly pathogenic H5N1 isolates. Whereas TROVAC-H5 AI H5 efficacy was not inhibited by anti-AI or anti-fowlpox maternal antibodies (passive immunity), protection to AI was significantly decreased in chickens previously vaccinated or infected with FP (active immunity). Advantages of the TROVAC-H5 vaccine over inactivated AI vaccines are: (a) single administration at 1 day of age and early onset (1 week) of protection, (b) easy monitoring of AI infection in vaccinated flocks with agar gel precipitation (AGP) and enzyme-linked immunosorbent assay (ELISA) used as tests to differentiate infected from vaccinated animals (DIVA tests), and (c) no residue problem due to adjuvant. These features make TROVAC-H5 an ideal AI vaccine for routine administration of day-of-age chicks in hatcheries. RecFP expressing HA from three lineages of H7 subtype (Eurasian, American, and Australian) were also tested for efficacy against a highly pathogenic avian influenza (HPAI) Eurasian HPAI H7N1. Only the recFP expressing the Eurasian H7 gene provided sufficient protection indicating that the breadth of protection induced by recFP is apparently restricted for H7 isolates. The fowlpox vector technology can also be used for the production of an emergency vaccine: once the HA sequence of an emerging AI virus is known, recFP can be rapidly generated. TROVAC-H5 has recently been shown to be immunogenic in cats and could therefore also be considered for use in mammals.

Abstract: The advent of recombinant DNA techniques and advances in immunology have provided a means for dissecting the immunobiology of disease-causing agents. Identification and expression of individual genes from the pathogens in heterologous systems, such as VV, have yielded valuable information regarding structural properties of the gene products and their role in eliciting protective immunity. Targets of both humoral and/or cellular immunity for many disease-causing agents have been identified or confirmed using a VV expression system (Section IV). Additionally, specific VV recombinants have induced a protective immune response in experimental animals. The ability of VV recombinants to induce pertinent immune responses necessary for protection, the potential to develop polyvalent vaccines, and the successful history of VV as an immunizing agent provide the impetus for engineering VV as a live recombinant vaccine candidate. Critical to the refinement of poxviruses as recombinant immunizing agents is a more in-depth knowledge of the molecular biology of these viruses. Although significant advances have been made in this area within the past 10 years, a greater understanding of the mechanisms governing gene expression and viral virulence factors should enable the development of more safe and effective vaccine candidates. Progression of VV vector technology to other members of the poxvirus family has been successful. Development of other poxviruses as vectors may, therefore, provide a means of generating host-restricted vaccines. Fowlpox recombinant viruses, for instance, may yield candidate vaccines in the poultry industry. Interestingly, it was also demonstrated that these host-restricted recombinant viruses can be used as immunizing vehicles in other species. The ability of a nonreplicating viral vector to elicit a protective immune response is especially intriguing in light of the observation by Morgan et al. that a VV/EBV gp340/220 recombinant, derived from an avirulent VV strain, was unable to protect cottontop tamarins from a live EBV challenge.