Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/29/2009
Publication Date: 10/6/2009
Citation: Jadhao, S.J., Lee, C., Sylte, M.J., Suarez, D.L. 2009. Comparative efficacy of North American and antigenically matched reverse genetics derived H5N9 DIVA marker vaccines against highly pathogenic Asian H5N1 avian influenza in chickens. Vaccine. 27:6247-6260.
Interpretive Summary: Avian influenza virus can cause a mild to severe disease in poultry. The highly virulent form of the virus, which causes high mortality in chickens, is called highly pathogenic avian influenza. The recent emergence of one particular strain of highly pathogenic avian influenza, H5N1 Asian lineage, has been the most severe causing outbreaks in over 60 countries on 3 continents. Vaccination is used as a control tool in several countries, and the most commonly used vaccines are killed influenza virus. This type of vaccine can provide good protection, but it is difficult to separate by antibody tests which birds were vaccinated and which were naturally infected. This study looked at ways to make new vaccines using the current technology of killed vaccines that allows differentiation of infected from vaccinated birds (DIVA). We demonstrated that vaccines made with an rare neuraminidase subtype gene, natural found in avian influenza viruses, provided good protection in experimental studies, and that it could be used as a DIVA vaccine. This approach can provide additional tools to control avian influenza in the field.
Technical Abstract: Highly pathogenic (HP) H5N1 avian influenza has become endemic in several countries in Asia and Africa, and vaccination is being widely used as a control tool. However, there is a need for efficacious vaccines preferably utilizing a DIVA (differentiate infected from vaccinated animals) marker strategy to allow for improved surveillance of influenza in poultry. Using a reverse genetics approach, we generated Asian rgH5N9 vaccine strain deriving the hemagglutinin gene from A/chicken/Indonesia/7/2003 (H5N1) with modification of the cleavage site to be low pathogenic (LP) and a neuraminidase gene from a North American LP A/turkey/Wisconsin/1968 (H5N9) virus. The recombinant rgH5N9, A/turkey/Wisconsin/1968 (H5N9) A/chicken/Hidalgo/232/1994 (H5N2), and wild type HP A/chicken/Indonesia/7/2003 (H5N1) viruses were used to prepare inactivated oil emulsified whole virus vaccines. Two weeks after vaccination, chickens were challenged with either Asian HP H5N1 viruses, A/chicken/Indonesia/07/2003 (WHO clade 2.1) or A/chicken/Supranburi Thailand /2/2004 (WHO clade 1.0). The H5 HA1 of the North American vaccine strains exhibited 12% amino acid differences including amino acid changes in the major antigenic sites as compared to the Asian HP H5N1 challenge viruses, serologically exhibited substantial antigenic difference, but still provided 100% protection from mortality. However, challenge virus shedding was significantly higher in chickens receiving American lineage vaccines as compared to the antigenically matched Asian rgH5N9 and the wild type Asian H5N1 vaccine. This study demonstrates the value of using a vaccine containing antigenically matched H5 hemagglutinin for control of HP H5N1 avian influenza in poultry and the potential utility of a heterologous neuraminidase as a DIVA marker.