Preparation of a standardized, efficacious agricultural H5N3 vaccine by reverse genetics

Ming Liu, John M. Wood , Trevor Ellis, Scott Krauss, Patrick Seiler, Christie Johnson, Erich Hoffmann, Jennifer Humber, Diane Hulse, Yun Zhang, Robert G. Webster  and Daniel R. Perez

Abstract
Biosecurity measures and vaccination with inactivated vaccines are options for the control of  avian influenza H5N1.

Commercially available H5N2 influenza vaccine prevents disease signs and reduces virus load but does not completely prevent virus shedding after challenge with H5N1 virus.

In this study an H5N3 vaccine was prepared using reverse genetics. The N3 neuraminidase, derived from A/Duck/Germany/1215/73 (H2N3), permitted discrimination between vaccinated and naturally infected birds.

 The virus construct failed to replicate in quail and chickens. Similar to parental A/PR/8/34 (H1N1), it replicated in mice and ferrets and spread to the brains of mice; therefore, it should not be used as a live-attenuated vaccine.

The H5N3 vaccine induced HI antibodies in chickens and prevented death, signs of disease, and markedly reduced virus shedding after challenge with A/CK/HK/86.3/02 (H5N1) but did not provide sterilizing immunity.

Thus, reverse genetics allows the inexpensive preparation of standardized, efficacious H5N3 poultry vaccines that may also reduce the re-emergence of H5N1 genotypes.