Kodihalli S, Goto H, Kobasa D L, Krauss S, Kawaoka Y, Webster R G
Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
J Virol. 1999 Mar;73(3):2094-8. doi: 10.1128/JVI.73.3.2094-2098.1999.
In Hong Kong in 1997, a highly lethal H5N1 avian influenza virus was apparently transmitted directly from chickens to humans with no intermediate mammalian host and caused 18 confirmed infections and six deaths. Strategies must be developed to deal with this virus if it should reappear, and prospective vaccines must be developed to anticipate a future pandemic. We have determined that unadapted H5N1 viruses are pathogenic in mice, which provides a well-defined mammalian system for immunological studies of lethal avian influenza virus infection. We report that a DNA vaccine encoding hemagglutinin from the index human influenza isolate A/HK/156/97 provides immunity against H5N1 infection of mice. This immunity was induced against both the homologous A/HK/156/97 (H5N1) virus, which has no glycosylation site at residue 154, and chicken isolate A/Ck/HK/258/97 (H5N1), which does have a glycosylation site at residue 154. The mouse model system should allow rapid evaluation of the vaccine's protective efficacy in a mammalian host. In our previous study using an avian model, DNA encoding hemagglutinin conferred protection against challenge with antigenic variants that differed from the primary antigen by 11 to 13% in the HA1 region. However, in our current study we found that a DNA vaccine encoding the hemagglutinin from A/Ty/Ir/1/83 (H5N8), which differs from A/HK/156/97 (H5N1) by 12% in HA1, prevented death but not H5N1 infection in mice. Therefore, a DNA vaccine made with a heterologous H5 strain did not prevent infection by H5N1 avian influenza viruses in mice but was useful in preventing death.
1997年在香港，一种高致死性H5N1禽流感病毒显然直接从鸡传染给人类，没有中间哺乳动物宿主，导致18例确诊感染和6人死亡。如果这种病毒再次出现，必须制定应对策略，还必须研发前瞻性疫苗以应对未来的大流行。我们已确定未适应的H5N1病毒对小鼠具有致病性，这为致死性禽流感病毒感染的免疫学研究提供了一个明确的哺乳动物系统。我们报告，一种编码来自人类流感首例分离株A/HK/156/97血凝素的DNA疫苗可使小鼠获得针对H5N1感染的免疫力。这种免疫力针对同源的A/HK/156/97（H5N1）病毒（其在154位残基处没有糖基化位点）以及鸡分离株A/Ck/HK/258/97（H5N1）（其在154位残基处有糖基化位点）均有诱导作用。小鼠模型系统应能在哺乳动物宿主中快速评估该疫苗的保护效力。在我们之前使用禽类模型的研究中，编码血凝素的DNA可对与主要抗原在HA1区域相差11%至13%的抗原变异株攻击提供保护。然而，在我们目前的研究中，我们发现一种编码来自A/Ty/Ir/1/83（H5N8）血凝素的DNA疫苗（其在HA1中与A/HK/156/97（H5N1）相差12%）可防止小鼠死亡，但不能预防H5N1感染。因此，用异源H5毒株制成的DNA疫苗不能预防小鼠感染H5N1禽流感病毒，但有助于预防死亡。
