DEVELOPMENT, STANDARDIZATION AND USE OF INFLUENZA VIRUS VACCINES

该计划旨在了解和改善流感病毒 包括流感病毒生物学的基础研究 复制以及临床研究的免疫学特性， 流感疫苗。甲型流感病毒是由甲型流感病毒 Rico/8/34（PR 8），H1N1毒株，作为增加产量和电流的供体 作为血凝素（HA）和神经氨酸酶供体的人甲型流感病毒 (NA)希望疫苗。抑制剂的基因组组成是 与复制能力相比。在一个系列中，125个中的不到10% 单卵后代H3抗性体产生类似于PR 8的HA（HAU）单位 最终发现它们都含有来自PR 8的NA的N1基因。虽然 N1基因片段并不总是在早期被鉴定， HAU转化为N1（有或没有PR 8基质基因）后， 后续通道。这表明NA有助于病毒活力， 低数量的持续H3 N1病毒粒子比 大多数H3 N2病毒粒子。这一发现适用于标准化 抑制剂的选择。 研究婴儿的免疫启动， 了解启动对随后流感反应的影响 疫苗先前的研究表明，自然感染的启动导致 对加强免疫的抗体应答的幅度大于 用现有的流感疫苗做初免。作为确认，婴儿 一岁以下的儿童随机接受减毒活疫苗的初免。 疫苗（H1N1）和灭活疫苗（H3 N2和B）或通过 灭活疫苗（H1N1、H3 N2和B）。再次免疫后， 灭活疫苗接种6个月后，几何平均滴度（GMT）和 血凝抑制（HI）的单个滴度明显高于 在接种活疫苗的婴儿中， 接种灭活疫苗的婴儿。两周内HI GMT 其他疫苗成分在两组之间没有差异， 婴儿。研究结果支持了以前的发现，并表明， 减毒疫苗可能为免疫引发提供上级策略 婴儿对流感病毒的抵抗力。

This program provides for understanding and improving influenza virus vaccines and includes basic studies of the biology of influenza virus replication as well as clinical studies of the immunologic properties of influenza vaccines. Reassortant influenza viruses are produced with A/Puert Rico/8/34 (PR8), an H1N1 strain, as a donor of increased yield and current human influenza A viruses as donors of hemagglutinin (HA) and neuraminidase (NA) desired for vaccines. The genomic composition of the reassortants is compared to the ability to replicate. In one series, less than 10% of 125 single egg progeny H3 reassortants yielded units of HA (HAU) similar to PR8 All ultimately were found to contain the N1 gene for NA from PR8. Although the N1 gene segment was not always identified early, all strains with high HAU converted to N1 (with or without PR8 matrix gene) after several subsequent passages. This indicates that NA contributes to viral vigor, tha low numbers of persisting H3N1 virions have survival advantage over the majority H3N2 virions. The finding is applicable to standardization of selection of reassortants. Immunologic priming in infants is studied to understand the impact of priming on subsequent responses to influenza vaccine. Previous studies indicate that priming by natural infection result in a greater magnitude of antibody response to booster immunization than does priming with current influenza vaccines. As a confirmation, infants under one year of age were randomized to receive priming by live attenuated vaccine (H1N1) and inactivated vaccine (H3N2 and B) or priming by inactivated vaccine (H1N1, H3N2 and B). After reimmunization with inactivated vaccine six months later, geometric mean titers (GMT) and individual titers for hemagglutination inhibition (HI) were clearly higher for H1N1 among the infants who were primed by live vaccine than for the infants who received inactivated vaccine for priming. GMTs by HI for the tw other vaccine components were no different between the two groups of infants. The results support previous findings and suggest that live attenuated vaccine may provide a superior strategy for immunologic priming of infants against influenza viruses.