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首页> 美国卫生研究院文献>Infection and Immunity >Live Victoria/75-ts-1E Influenza A Virus Vaccines in Adult Volunteers: Role of Hemagglutinin Immunity in Protection Against Illness and Infection Caused by Influenza A Virus
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Live Victoria/75-ts-1E Influenza A Virus Vaccines in Adult Volunteers: Role of Hemagglutinin Immunity in Protection Against Illness and Infection Caused by Influenza A Virus

机译：成人志愿者中的活维多利亚/ 75-ts-1 E甲型流感病毒疫苗：血凝素免疫在预防甲型流感病毒引起的疾病和感染中的作用

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摘要

To explore the relationship between neuraminidase immunity and the degree of attenuatíon of live influenza A virus vaccines, a comparative evaluation of three Victoria/75-ts-1[E] (Vic/75-ts-1[E]) recombinant viruses in serum hemagglutination-inhibiting-negative (titer, ≤1:8) adult volunteers was performed. These three ts-1[E] viruses had a similar restriction of replication at 38°C in vitro, and each possessed the two attenuating genes of the ts-1[E] donor strain (13). However, Vic/75-ts-1[E] recombinants 81 and 113 possessed both Vic/75 hemagglutinin (H375) and Vic/75 neuraminidase (N275), whereas Vic/75-ts-1[E] recombinant 67 had Vic/75 hemagglutinin but the N265 neuraminidase. Vic/75-ts-1[E] recombinant 67 was significantly more attenuated than Vic/75-ts-1[E] recombinants 81 and 113 in that fewer local and systemic signs and symptoms of illness were observed in those volunteers who received clone 67. These findings were consistent with our previous observations which suggested that the following two factors contribute to the attenuation of ts-1[E] vaccine strains in adults: (i) the attenuating effect of the two ts-1[E] genes and (ii) the neuraminidase immunity of the host. Vic/75-ts-1[E] recombinant clone 67 vaccinees developed an immunological response to the H375 hemagglutinin in the absence of a response to the N275 neuraminidase. To assess the role that anti-hemagglutinin immunity induced by an attenuated live virus vaccine plays in resistance to influenza A virus, vaccinees who received recombinant 67 were challenged with Vic/75 wild-type virus, and their responses were compared with those of Vic/75-ts-1[E] vaccinees who received recombinant 81 or 113. Each of the three groups of ts-1[E] vaccinees was significantly protected against illness induced by wild-type virus infection, although resistance was not complete. However, the clone 67 vaccinees were protected less against infection. The infection-permissive resistance induced by clone 67 resembled that previously described for inactivated neuraminidase-specific vaccines. These results suggested that a ts-1[E] recombinant that possessed the hemagglutinin of a new pandemic variant, the neuraminidase of the preceding subtype, and the two ts-1[E] ts genes would be satisfactorily attenuated for children and adults with neuraminidase immunity and could induce resistance to illness caused by the new pandemic wild-type influenza A virus.
机译：为了探讨神经氨酸酶免疫力与活甲型流感病毒疫苗减毒程度之间的关系，对三种血清中的Victoria / 75-ts-1 [E]（Vic / 75-ts-1 [E]）重组病毒进行比较评估进行血凝抑制阴性（滴度，≤1：8）成年志愿者。这三种ts-1 [E]病毒在38°C的体外具有类似的复制限制，并且各自具有ts-1 [E]供体菌株的两个减毒基因（13）。但是，Vic / 75-ts-1 [E]重组体81和113同时具有Vic / 75血凝素（H375）和Vic / 75神经氨酸酶（N275），而Vic / 75-ts-1 [E]重组体67具有Vic / 75血凝素，但N265神经氨酸酶。 Vic / 75-ts-1 [E]重组体67比Vic / 75-ts-1 [E]重组体81和113显着减弱，因为在接受克隆的志愿者中观察到的局部和全身性疾病迹象和症状较少67.这些发现与我们以前的观察结果一致，表明以下两个因素有助于成人ts-1 [E]疫苗株的减毒：（i）两个ts-1 [E]基因的减毒作用和（ii）宿主的神经氨酸酶免疫力。 Vic / 75-ts-1 [E]重组克隆67个疫苗在没有对N275神经氨酸酶的应答的情况下对H375血凝素产生了免疫应答。为了评估减毒活病毒疫苗诱导的抗血凝素免疫在抵抗甲型流感病毒中的作用，接受重组67疫苗的疫苗受到Vic / 75野生型病毒的攻击，并将其反应与Vic / 75进行比较。接受重组81或113的75-ts-1 [E]疫苗。三组ts-1 [E]疫苗中的每一组都得到了明显的保护，可以抵抗野生型病毒感染引起的疾病，尽管耐药性还不完全。但是，克隆67种疫苗接种者受到的保护较少，不会受到感染。克隆67诱导的允许感染的抗药性类似于先前针对灭活的神经氨酸酶特异性疫苗所描述的抗药性。这些结果表明，对于具有神经氨酸酶的儿童和成人，具有新大流行变体血凝素，先前亚型的神经氨酸酶和两个ts-1 [E] ts基因的ts-1 [E]重组体将令人满意地减毒。免疫力，并可以诱导对新型大流行野生型A型流感病毒引起的疾病的抵抗力。

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