Multivalent HA DNA Vaccination Protects against Highly Pathogenic H5N1 Avian Influenza Infection in Chickens and Mice

Srinivas Rao,Hongquan Wan,Daniel Perez,Darrel Styles,Wing-Pui Kong,Chih-Jen Wei,Erin M Sorrell,Zhi-Yong Yang,Martha Nason,Louis J Detolla,Gary J Nabel,Haichen Song,Gloria C Ramirez-Nieto,David M Ojcius

doi:10.1371/journal.pone.0002432

Abstract

BackgroundSustained outbreaks of highly pathogenic avian influenza (HPAI) H5N1 in avian species increase the risk of reassortment and adaptation to humans. The ability to contain its spread in chickens would reduce this threat and help maintain the capacity for egg-based vaccine production. While vaccines offer the potential to control avian disease, a major concern of current vaccines is their potency and inability to protect against evolving avian influenza viruses.Methodology / Principal FindingsThe ability of DNA vaccines encoding hemagglutinin (HA) proteins from different HPAI H5N1 serotypes was evaluated for its ability to elicit neutralizing antibodies and to protect against homologous and heterologous HPAI H5N1 strain challenge in mice and chickens after DNA immunization by needle and syringe or with a pressure injection device. These vaccines elicited antibodies that neutralized multiple strains of HPAI H5N1 when given in combinations containing up to 10 HAs. The response was dose-dependent, and breadth was determined by the choice of the influenza virus HA in the vaccine. Monovalent and trivalent HA vaccines were tested first in mice and conferred protection against lethal H5N1 A/Vietnam/1203/2004 challenge 68 weeks after vaccination. In chickens, protection was observed against heterologous strains of HPAI H5N1 after vaccination with a trivalent H5 serotype DNA vaccine with doses as low as 5 µg DNA given twice either by intramuscular needle injection or with a needle-free device.Conclusions/SignificanceDNA vaccines offer a generic approach to influenza virus immunization applicable to multiple animal species. In addition, the ability to substitute plasmids encoding different strains enables rapid adaptation of the vaccine to newly evolving field isolates.

Highlights

The highly pathogenic H5N1 influenza virus causes lethal multi-organ disease in poultry, resulting in significant economic losses and a public health concern in many parts of the world
The findings suggest that it is possible to develop a multivalent DNA vaccine for poultry that can protect against multiple highly pathogenic avian influenza (HPAI) H5N1 strains and that could keep pace with the continued evolution of avian influenza viruses
Animals were immunized with each expression vector intramuscularly (IM) at three week intervals, and the antisera were evaluated on day 14 after the third immunization for their ability to neutralize HPAI H5N1 pseudotyped lentiviral vectors as previously described [35,36]

Summary

Introduction

The highly pathogenic H5N1 influenza virus causes lethal multi-organ disease in poultry, resulting in significant economic losses and a public health concern in many parts of the world. DNA vaccines have been shown to elicit robust immune responses in various animal species, from mice to nonhuman primates [1,2,3,4,5,6,7,8,9,10,11] In human trials, these vaccines elicit cellular and humoral immune responses against various infectious agents, including influenza, SARS, SIV and HIV. These vaccines elicit cellular and humoral immune responses against various infectious agents, including influenza, SARS, SIV and HIV In addition to their ability to elicit antibody responses, they stimulate antigenspecific and sustained T cell responses [1,2,3,6,12,13]. While vaccines offer the potential to control avian disease, a major concern of current vaccines is their potency and inability to protect against evolving avian influenza viruses

Methods

Results

Conclusion