Evaluation of live avian-human reassortant influenza A H3N2 and H1N1 virus vaccines in seronegative adult volunteers.
Evaluation of live avian-human reassortant influenza A H3N2 and H1N1 virus vaccines in seronegative adult volunteers.
复制标题
在血清阴性成年志愿者中评估活禽-人重配甲型 H3N2 和 H1N1 流感病毒疫苗。
DOI：
10.1128/jcm.23.5.852-857.1986
复制
发表时间：
1986
影响因子：
9.4
通讯作者：
Murphy,BR
中科院分区：
文献类型：
--
作者：
Snyder,MH;Clements,ML;Betts,RF;Dolin,R;Buckler-White,AJ;Tierney,EL;Murphy,BR
一种禽-人抗流感A病毒，其编码血凝素和神经氨酸酶的基因来自人流感A/华盛顿/897/80（H3 N2）病毒，其六个“内部”基因来自禽流感A/野鸭/NY/6750/78（H2 N2）病毒（即，一种六基因重组子）以前被证明是安全的、传染性的、非传染性的，并且作为成年人的活病毒疫苗是免疫原性的。另外两种来源于野生型人流感A/加州/10/78（H1 N1）和A/韩国/1/82（H3 N2）病毒与禽流感A/野鸭/NY/78病毒交配的6基因禽-人流感病毒在血清阴性中进行了评价，（血凝抑制滴度，小于或等于1：8）成年志愿者的安全性，传染性，和免疫原性，以确定是否可以通过转移禽流感A/Mallard/NY/78病毒的六个内部基因来可重复地减毒人流感A病毒。50%人感染剂量为H1N1抗病毒的10（4.9）50%组织培养感染剂量和H3 N2抗病毒的10（5.4）50%组织培养感染剂量。这两个rereflectants是令人满意的减毒只有5%（H1N1）和2%（H3 N2）的感染疫苗接受不到400 - 50%的人类感染剂量发展疾病。与这种减毒水平一致，与野生型病毒产生的病毒相比，接种后病毒脱落的幅度降低了100倍（H1N1）至10，000倍（H3 N2）。疫苗的病毒脱落持续时间是接受野生型病毒的对照的三分之一。在40至100 50%的人类感染剂量，病毒特异性免疫反应，在77%至93%的志愿者。当接种了10（7.5）50%组织培养感染剂量的H3 N2疫苗的接种者用同源野生型人病毒进行实验性攻击时，19名接种者中只有2名（11%）患病，而14名未接种血清阴性对照中有7名（50%）患病（P < 0.025;保护效力，79%）。因此，通过获得禽流感A/Mallard/NY/78病毒的六个内部基因，已经令人满意地减毒了三种不同的毒性人流感A病毒。观察到这种供体病毒可以可重复地减毒人甲型流感病毒，这表明禽-人甲型流感疫苗应作为潜在的甲型流感病毒活疫苗进行进一步研究。
An avian-human reassortant influenza A virus deriving its genes coding for the hemagglutinin and neuraminidase from the human influenza A/Washington/897/80 (H3N2) virus and its six "internal" genes from the avian influenza A/Mallard/NY/6750/78 (H2N2) virus (i.e., a six-gene reassortant) was previously shown to be safe, infectious, nontransmissible, and immunogenic as a live virus vaccine in adult humans. Two additional six-gene avian-human reassortant influenza viruses derived from the mating of wild-type human influenza A/California/10/78 (H1N1) and A/Korea/1/82 (H3N2) viruses with the avian influenza A/Mallard/NY/78 virus were evaluated in seronegative (hemagglutination inhibition titer, less than or equal to 1:8) adult volunteers for safety, infectivity, and immunogenicity to determine whether human influenza A viruses can be reproducibly attenuated by the transfer of the six internal genes of the avian influenza A/Mallard/NY/78 virus. The 50% human infectious dose was 10(4.9) 50% tissue culture infectious doses for the H1N1 reassortant virus and 10(5.4) 50% tissue culture infectious doses for the H3N2 reassortant virus. Both reassortants were satisfactorily attenuated with only 5% (H1N1) and 2% (H3N2) of infected vaccines receiving less than 400 50% human infectious doses developing illness. Consistent with this level of attenuation, the magnitude of viral shedding after inoculation was reduced 100-fold (H1N1) to 10,000-fold (H3N2) compared with that produced by wild-type virus. The duration of virus shedding by vaccines was one-third that of controls receiving wild-type virus. At 40 to 100 50% human infectious doses, virus-specific immune responses were seen in 77 to 93% of volunteers. When vaccinees who has received 10(7.5) 50% tissue culture infectious doses of the H3N2 vaccine were experimentally challenged with a homologous wild-type human virus only 2 of 19 (11%) vaccinees became ill compared with 7 of 14 (50%) unvaccinated seronegative controls ( P < 0.025; protective efficacy, 79%). Thus, three different virulent human influenza A viruses have been satisfactorily attenuated by the acquisition of the six internal genes of the avian influenza A/Mallard/NY/78 virus. The observation that this donor virus can reproducibly attenuate human influenza A viruses indicates that avian-human influenza A reassortants should be further studied as potential live influenza A virus vaccines.