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Title: Development and evaluation of a potential universal Salmonella-vectored avian influenza vaccine

item HARGIS, B
item LAYTON, S
item Kapczynski, Darrell
item COLE, K
item COX, M
item YWON, Y
item Liljebjelke, Karen
item BOTTJE, W

Submitted to: Poultry Science Association Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 6/10/2008
Publication Date: 7/20/2008
Citation: Hargis, B.M., Layton, S.L., Kapczynski, D.R., Cole, K., Cox, M.M., Ywon, Y.M., Bergham, L.R., Liljebjelke, K.A., Bottje, W.J. 2008. Development and evaluation of a potential universal Salmonella-vectored avian influenza vaccine [abstract]. Poultry Science Association Centennial Meeting, July 20-23, 2008, Ontario, Canada. CDROM.

Interpretive Summary:

Technical Abstract: Development of vaccines for effective control of avian influenza (AI) virus in poultry and wild birds is in high demand. Most AI vaccines target the immunodominant antigens such as hemagglutinin (HA) and neuraminidase (NA); however, these vaccines only provide protection against a particular AI serotype. Among the many vaccine strategies, bacterial vectored vaccines expressing an antigenic property of AI are a promising strategy. We have recently created a Salmonella-based AI vaccine which targets the extracellular domain of the universally conserved ion channel protein M2 or M2e. Antibodies against M2e have previously been shown to provide protection against influenza challenge. Wild type Salmonella enteritidis 13A was attenuated (del-aroA/del-htrA) and the genome manipulated to express M2e protein epitopes (M2e: EVETPIRN, EVETPTRN) as a fusion with the outer membrane protein LamB. In addition, a short 10aa sequence of CD154 (WAEKGYYTMS) was inserted to test its potential immune-enhancing function. Following vaccination with the Salmonella recombinant vaccine, chickens demonstrated significantly increased M2e-specific IgG antibody titers. Virus neutralization assays in chicken embryos resulted in neutralizing titers in the range of 5.8-6.3 (log2), indicating the antibodies induced were effective at neutralizing AI. Direct sub-lethal challenge of vaccinated chicks with A/Turkey/Virginia/158512/2002 (TV/02) H7N2 low pathogen AI (LPAI) and A/Egret/Hong Kong/757.2/2002 (Eg/02) H5N1 high pathogenic AI (HPAI) viruses showed a significant decrease in morbidity and duration of clinical signs. However, protection from mortality was not observed against direct lethal challenge with HPAI in a subsequent trial. These data suggest that this candidate vaccine may provide broad protection against LPAI, however additional epitopes might be required for protection against lethal HPAI challenge.