Development and use of fowlpox vectored vaccines for avian influenza

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.