Submitted to: Vaccine
Publication Type: Peer reviewed journal
Publication Acceptance Date: 1/15/2004
Publication Date: 8/1/2004
Citation: Lee, C.W., Senne, D., Suarez, D.L. 2004. Generation of Reassortant Influenza Vaccines By Reverse Genetics That Allows Utilization Of A Diva (Differentiating Infected From Vaccinated Animals)Strategy For The Control Of Avian Influenza. Vaccine 22(2004) 3175-3181. Interpretive Summary: Avian influenza can cause either a mild or serious disease in poultry depending on the strain of the virus. Vaccination has been one method used to try to control the disease. Two subtypes of avian influenza, the H5 and H7 subtype, are of greatest concern, because these are the subtypes that can cause the severe disease. Even though most H5 or H7 viruses in poultry cause only the mild disease, many of the U.S. foreign trading partners will not accept our poultry if infected with either the H5 or H7 subtype because of concern that the virus may change to the more virulent form. Our trading partners also have not accepted vaccinated birds, because in the past it was difficult to determine if the birds had been vaccinated or naturally infected with influenza virus. Therefore we typically have not vaccinated for H5 or H7 influenza, but instead have used potentially more expensive eradication programs. We created a new vaccine whch allows us to easily differentiate the birds that were naturally infected with influenza from those that were vaccinated. This is called a DIVA strategy. The DIVA strategy can potentially allow U.S. poultry producers to use vaccination to control mild H5 or H7 outbreaks, and still potentially be able to market our poultry to our foreign markets.
Technical Abstract: Vaccination of poultry with inactivated influenza vaccine can be an effective tool in the control of avian influenza (AI). One major concern of using inactivated vaccine is vaccine-induced antibody interference with serologic surveillance and epidemiology. In the United States, low pathogenic H5 and H7 subtype AI viruses have routinely caused problems in the poultry industry. Most of these viruses also have the accompanying N2 subtype and no H5N1 or H7N8 subtype AI viruses have been identified in poultry in the U.S. In order to allow the differentiation of infected from vaccinated animals (DIVA) while maintaining maximum efficacy of the vaccine, we generated reassortant viruses by reverse genetics that contained the same H5 and H7 hemagglutinin (HA) gene as the challenge virus, but a heterologous N1 or N8 neuraminidase (NA) gene. In vaccination-challenge experiments in 2-week-old specific pathogen free chickens, reassortant influenza vaccines (rH5N1 and rH7N8) demonstrated similar antibody profiles and comparable protection rates as homologous H5N2 and H7N2 vaccines. Further, we were able to differentiate the sera from infected and vaccinated birds by neuraminidase inhibition test and indirect immunofluorescent antibody assay on the basis of different antibodies elicited by their NA proteins. These results demonstrate the usefulness of a reverse genetic system for the rapid generation of reassortant AI virus that allows utilization of the DIVA strategy for the control of AI infections in poultry.