DNA vaccine expressing conserved influenza virus proteins protective against H5N1 challenge infection in mice.
Influenza vaccination practice, which is based on neutralizing antibodies, requires being able to predict which viral strains will be circulating. If an unexpected strain, as in the 1997 H5N1 Hong Kong outbreak, or even a pandemic emerges, appropriate vaccines may take too long to prepare. Therefore, strategies based on conserved influenza antigens should be explored. We studied DNA vaccination in mice with plasmids expressing conserved nucleoprotein (NP) and matrix (M) from an H1N1 virus. After vaccination, mice were challenged with A/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). After HK/156 exposure, mice survived rechallenge with A/Hong Kong/483/97 (HK/483), although the DNA vaccination alone protected poorly against this highly virulent strain. In the absence of antigenically matched hemagglutinin-based vaccines, DNA vaccination with conserved influenza genes may provide a useful first line of defense against a rapidly spreading pandemic virus.
Food and Drug Administration, Rockville, Maryland 20852-1448, USA. epsteins@cber.fda.gov
Suzanne L
SL
Epstein
Terrence M
TM
Tumpey
Julia A
JA
Misplon
Chia-Yun
CY
Lo
Lynn A
LA
Cooper
Kanta
K
Subbarao
Mary
M
Renshaw
Suryaprakash
S
Sambhara
Jacqueline M
JM
Katz
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology*; D029521:Alphainfluenzavirus / Q000145:classification / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control*; D010957:Plasmids / Q000235:genetics; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D007252:Influenza Vaccines; D019444:Vaccines, DNA