IMMUNIZATION WITH PURIFIED N1 AND N2 INFLUENZA-VIRUS NEURAMINIDASES DEMONSTRATES CROSS-REACTIVITY WITHOUT ANTIGENIC-COMPETITION
IMMUNIZATION WITH PURIFIED N1 AND N2 INFLUENZA-VIRUS NEURAMINIDASES DEMONSTRATES CROSS-REACTIVITY WITHOUT ANTIGENIC-COMPETITION
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DOI：
10.1073/pnas.91.6.2358
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发表时间：
1994-03-15
影响因子：
11.1
通讯作者：
KILBOURNE, ED
中科院分区：
文献类型：
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作者：
JOHANSSON, BE;KILBOURNE, ED
基于缺乏血清学交叉反应性，甲型流感病毒的神经氨酸酶（NAs）被分为抗原离散亚型，类似于它们共享病毒粒子表面的血凝素（HA）主要抗原。一种创新的流感疫苗接种方法利用了NA作为次要表面抗原免疫的感染容许性。然而，有证据表明，当HA和NA一起出现在完整的病毒粒子中时，HA主导免疫反应，这促使人们对最终需要用于人类疫苗接种的NA亚型混合物免疫过程中可能存在的竞争效应进行研究。纯化的N1-和n2亚型NAs免疫BALB/c小鼠，在原发性或继发性应答中没有抗原竞争。然而，当免疫后感染同型或异型时，发现N1和N2之间存在交叉反应性抗体，并且“反向抗原竞争”发生，初始NA引物抑制含有同源NA的病毒感染后对HA的反应。这些抗原混合物的研究对在流感以外的疾病中使用联合抗原嵌合疫苗具有启示意义。
Based on the absence of serologic crossreactivity, the neuraminidases (NAs) of influenza A viruses are divided into antigenically discrete subtypes, analogous to the hemagglutinin (HA) major antigens with which they share the virion surface. An innovative approach to influenza vaccination takes advantage of the infection-permissive nature of immunization with NA as the minor surface antigen. However, evidence that HA dominates immune response when HA and NA are presented together in the intact virion prompted investigation of possible competing effects during immunization of NA subtype mixtures ultimately required for human vaccination. Immunization of BALB/c mice with purified N1- and N2-subtype NAs demonstrated no antigenic competition in primary or secondary response. However, when homotypic or heterotypic infection followed immunization, cross-reactive antibodies between N1 and N2 were found and ''reverse antigen competition'' occurred with initial NA priming suppressing response to HA following infection with virus containing homologous NA. These studies of antigen mixtures have implications for the use of combined ana chimeric vaccines for diseases other than influenza.