Kreijtz J H C M, Bodewes R, van Amerongen G, Kuiken T, Fouchier R A M, Osterhaus A D M E, Rimmelzwaan G F
Department of Virology, Erasmus Medical Centre, P.O. Box 1738, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
Vaccine. 2007 Jan 8;25(4):612-20. doi: 10.1016/j.vaccine.2006.08.036. Epub 2006 Sep 7.
In order to assess the level of protection against a lethal influenza virus infection provided by a primary infection with a virus strain of another subtype, C57BL/6 mice were infected with the sublethal influenza virus X-31 (H3N2) and subsequently challenged with the lethal strain A/PR/8/34 (H1N1). The outcome of the challenge infection was compared with that in mice that did not experience an infection with influenza virus X-31 prior to the challenge infection. The X-31 experienced mice cleared the infection with influenza virus A/PR/8/34 in an accelerated fashion, displayed less clinical signs and a reduction of lesions in the lungs resulting in improved survival rates of these mice compared to the naive mice. The improved outcome of the challenge infection with influenza virus A/PR/8/34 in the X-31 experienced mice correlated with priming for anamnestic virus-specific CD8(+) cytotoxic T lymphocyte (CTL) responses as was demonstrated by the detection of CTL specific for the H-2D(b) restricted NP(366-374) epitope that was shared by the influenza viruses X-31 and A/PR/8/34. Thus previous exposure to influenza A viruses affords partial protection against infection in the absence of virus-neutralizing antibodies specific for the hemagglutinin and the neuraminidase. The implications of these observations are discussed in the light of the current pandemic threat and development of vaccines that aim at the induction of virus-specific CTL.
为了评估由另一种亚型病毒株的初次感染所提供的针对致死性流感病毒感染的保护水平，将C57BL/6小鼠感染亚致死性流感病毒X-31（H3N2），随后用致死性毒株A/PR/8/34（H1N1）进行攻击。将攻击感染的结果与在攻击感染前未感染流感病毒X-31的小鼠的结果进行比较。经历过X-31感染的小鼠以加速方式清除了A/PR/8/34流感病毒感染，表现出较少的临床症状，肺部病变减少，与未感染的小鼠相比，这些小鼠的存活率提高。在经历过X-31感染的小鼠中，A/PR/8/34流感病毒攻击感染的改善结果与记忆性病毒特异性CD8(+)细胞毒性T淋巴细胞（CTL）反应的启动相关，这通过检测对H-2D(b)限制性NP(366-374)表位具有特异性的CTL得以证明，该表位由流感病毒X-31和A/PR/8/34共享。因此，既往接触甲型流感病毒在缺乏针对血凝素和神经氨酸酶的病毒中和抗体的情况下能提供部分抗感染保护。根据当前的大流行威胁以及旨在诱导病毒特异性CTL的疫苗的研发，对这些观察结果的意义进行了讨论。
