Low pathogenic avian influenza (H9N2) in chicken: Evaluation of an ancestral H9-MVA vaccine.
Modified Vaccinia Ankara (MVA) has proven its efficacy as a recombinant vector vaccine for numerous pathogens including influenza virus. The present study aimed at evaluating a recombinant MVA candidate vaccine against low pathogenic avian influenza virus subtype H9N2 in the chicken model. As the high genetic and antigenic diversity of H9N2 viruses increases vaccine design complexity, one strategy to widen the range of vaccine coverage is to use an ancestor sequence. We therefore generated a recombinant MVA encoding for the gene sequence of an ancestral hemagglutinin H9 protein (a computationally derived amino acid sequence of the node of the H9N2 G1 lineage strains was obtained using the ANCESCON program). We analyzed the genetics and the growth properties of the MVA vector virus confirming suitability for use under biosafety level 1 and tested its efficacy when applied either as an intra-muscular (IM) or an oral vaccine in specific pathogen free chickens challenged with A/chicken/Tunisia/12/2010(H9N2). Two control groups were studied in parallel (unvaccinated and inoculated birds; unvaccinated and non-inoculated birds). IM vaccinated birds seroconverted as early as four days post vaccination and neutralizing antibodies were detected against A/chicken/Tunisia/12/2010(H9N2) in all the birds before challenge. The role of local mucosal immunity is unclear here as no antibodies were detected in eye drop or aerosol vaccinated birds. Clinical signs were not detected in any of the infected birds even in absence of vaccination. Virus replication was observed in both vaccinated and unvaccinated chickens, suggesting the MVA-ancestral H9 vaccine may not stop virus spread in the field. However vaccinated birds showed less histological damage, fewer influenza-positive cells and shorter virus shedding than their unvaccinated counterparts.
IIHAP, Université de Toulouse, INRA, ENVT, Toulouse, France. Electronic address: m.ducatez@envt.fr.
Mariette F
MF
Ducatez
IIHAP, Université de Toulouse, INRA, ENVT, Toulouse, France; Lehrstuhl für Virologie, Institut für Infektionsmedizin und Zoonosen, Ludwig-Maximilians-Universität München Munich, Germany.
Jens
J
Becker
Lehrstuhl für Virologie, Institut für Infektionsmedizin und Zoonosen, Ludwig-Maximilians-Universität München Munich, Germany.
Astrid
A
Freudenstein
IIHAP, Université de Toulouse, INRA, ENVT, Toulouse, France.
Maxence
M
Delverdier
IIHAP, Université de Toulouse, INRA, ENVT, Toulouse, France.
Mattias
M
Delpont
Lehrstuhl für Virologie, Institut für Infektionsmedizin und Zoonosen, Ludwig-Maximilians-Universität München Munich, Germany.
Gerd
G
Sutter
IIHAP, Université de Toulouse, INRA, ENVT, Toulouse, France.
Jean-Luc
JL
Guérin
Lehrstuhl für Virologie, Institut für Infektionsmedizin und Zoonosen, Ludwig-Maximilians-Universität München Munich, Germany.
Asisa
A
Volz
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002645:Chickens; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology; D053127:Influenza A Virus, H9N2 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000592:standards*; D005585:Influenza in Birds / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D011201:Poultry Diseases / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D013047:Specific Pathogen-Free Organisms; D019444:Vaccines, DNA; D014616:Vaccinia virus / Q000235:genetics; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D006389:Hemagglutinins, Viral; D007252:Influenza Vaccines; C560489:MVA vaccine; D019444:Vaccines, DNA; D014765:Viral Vaccines
Chicken model; Influenza virus; Modified Vaccinia Ankara vector; Vaccine