Skip to main content
ARS Home » Research » Publications at this Location » Publication #128876
Title: DNA VACCINE EXPRESSING CONSERVED INFLUENZA VIRUS PROTEINS PROTECTS AGAINST CHALLENGE WITH H5N1 VIRUSES OF LOW OR INTERMEDIATE VIRULENCE IN MICE

Author
item EPSTEIN, SUZANNE - FDA - ROCKVILLE, MD
item Tumpey, Terrence
item MISPLON, JULIA - FDA - ROCKVILLE, MD
item CHIA-YUN, LO - FDA - ROCKVILLE, MD
item COOPER, LYNN - CDC - ATLANTA, GA
item SUBBARAO, KANTA - CDC - ATLANTA, GA
item RENSHAW, MARY - CDC - ATLANTA, GA
item SAMBHARA, SURYAPRAKASH - CDC - ATLANTA, GA
item KATZ, JACQUELINE - CDC - ATLANTA, GA

Submitted to: Emerging Infectious Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/13/2002
Publication Date: 8/1/2002
Citation: N/A

Interpretive Summary: In 1997 in Hong Kong, six deaths were recorded from eighteen confirmed H5N1 influenza cases and was the first time that a purely avian virus was shown to cause respiratory disease in humans. This outbreak has raised concern that conventional immunization strategies will have significant limitations. This is largely due to the fact that some avian viruses such as the 1997 Hong Kong H5N1 viruses are lytic to avian cells and are difficult or impossible to grow by conventional methods in embryonated chicken eggs. Production of vaccines against such viruses may also be complicated by the higher levels of biosafety containment required in the initial stages of development. Therefore, it is believed that different strategies need to be explored to improve the efficacy of the current influenza vaccine. We studied DNA vaccination in mice using genetic material expressing conserved influenza proteins. DNA vaccination reduced replication of several 1997 Hong Kong H5N1 viruses, however DNA vaccination alone did not protect against one highly virulent strain. this approach might be useful as a first line of defense against a rapidly spreading influenza pandemic, and should be further explored.

Technical Abstract: Current influenza vaccination based on neutralizing antibodies requires predicting which viral strains will be circulating. If unexpected strains, such as the H5N1 Hong Kong outbreak in 1997, or even a pandemic emerges, such vaccines may take too long to prepare, so strategies based on conserved influenza antigens should be explored. We studied DNA vaccination nin mice using plasmids expressing conserved nucleoprotein (NP) and matrix (M) from H1N1, and challenge with H5N1 viruses of low, intermediate, and high lethality. A/NP+A/M DNA vaccination reduced replication of A/Hong Kong/486/97 (HK/486), a nonlethal H5N1 strain, and protected against lethal challenge with more virulent A/Hong Kong/156/97 (HK/156). Following HK/156 exposure, mice survived rechallenge with A/Hong Kong/483/97 (HK/483), although the DNA vaccination alone did not protect against this highly virulent strain. In the absence of antigenically-matched HA-based vaccines, ,DNA vaccination with conserved influenza genes may provide a useful first line of defense against a rapidly spreading pandemic virus.