Cross-protection against H5N1 influenza virus infection is afforded by intranasal inoculation with seasonal trivalent inactivated influenza vaccine
Cross-protection against H5N1 influenza virus infection is afforded by intranasal inoculation with seasonal trivalent inactivated influenza vaccine
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DOI：
10.1086/521304
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发表时间：
2007-11-01
影响因子：
6.4
通讯作者：
Hasegawa, Hideki
中科院分区：
文献类型：
--
作者：
Ichinohe, Takeshi;Tamura, Shin-ichi;Hasegawa, Hideki
背景禽H5 N1甲型流感病毒是一种新出现的病原体，有可能导致人类大量发病和死亡。我们评估了目前批准的季节性流感疫苗在小鼠中对高致病性H5 N1流感病毒的交叉保护能力。BALB/c小鼠鼻内或皮下接种日本2005-2006年季节许可的三价灭活流感疫苗3次。疫苗包括A/NewCaledonia/20/99（H1N1）、A/NewYork/55/2004（H3 N2）和B/Shanghai/361/2002病毒株，并与作为佐剂的poly（I）：poly（C12 U）（Ampligen）一起施用。在最后一次接种后14天，用A/HongKong/483/97、A/Vietnam/1194/04或A/Indonesia/6/05株H5 N1流感病毒攻击接种小鼠。与未接种的小鼠相比，那些鼻内接种表现出交叉反应的粘膜伊加和血清IgG与H5 N1病毒，以及降低H5 N1病毒滴度在鼻洗样品和增加生存，与H5 N1病毒的挑战后。皮下接种不诱导交叉反应性伊加应答，也不提供抗H5 N1病毒感染的保护作用。鼻内接种每年一次的流感疫苗加上Toll样受体-3激动剂poly（I）：poly（C-12 U），可通过提供针对具有大流行潜力的H5 N1病毒的交叉保护性粘膜免疫来克服H5 N1病毒疫苗供应有限的问题。
Background. Avian H5N1 influenza A virus is an emerging pathogen with the potential to cause substantial human morbidity and mortality. We evaluated the ability of currently licensed seasonal influenza vaccine to confer cross-protection against highly pathogenic H5N1 influenza virus in mice.Methods. BALB/c mice were inoculated 3 times, either intranasally or subcutaneously, with the trivalent inactivated influenza vaccine licensed in Japan for the 2005-2006 season. The vaccine included A/NewCaledonia/20/99 (H1N1), A/NewYork/55/2004 (H3N2), and B/Shanghai/361/2002 viral strains and was administered together with poly(I): poly(C 12 U) (Ampligen) as an adjuvant. At 14 days after the final inoculation, the inoculated mice were challenged with either the A/HongKong/483/97, the A/Vietnam/1194/04, or the A/Indonesia/6/05 strain of H5N1 influenza virus.Results. Compared with noninoculated mice, those inoculated intranasally manifested cross-reactivity of mucosal IgA and serum IgG with H5N1 virus, as well as both a reduced H5N1 virus titer in nasal-wash samples and increased survival, after challenge with H5N1 virus. Subcutaneous inoculation did not induce a cross-reactive IgA response and did not afford protection against H5N1 viral infection.Conclusions. Intranasal inoculation with annual influenza vaccine plus the Toll-like receptor -3 agonist, poly(I): poly(C-12 U), may overcome the problem of a limited supply of H5N1 virus vaccine by providing cross-protective mucosal immunity against H5N1 viruses with pandemic potential.