Haaheim L R, Tomasov C C, Barr I G, Hampson A W, Komadina N
WHO Collaborating Centre for Reference and Research on Influenza, 45 Poplar Road, Parkville, Vic. 3052, Australia.
Vaccine. 2006 Nov 10;24(44-46):6708-11. doi: 10.1016/j.vaccine.2006.05.088. Epub 2006 Jun 12.
Antigenic variants probably arise in the field by escaping herd immunity. We have earlier found that sera from small children are more strain-specific than sera from adults and could therefore, provide favourable conditions for selecting antigenic escape mutants. We had access to small volumes of anonymous sera collected in Norway after the epidemic season 1999/00, which was dominated by the A/Panama/2007/99 (H3N2) variant. The HA gene of the representative strain of that season was genetically identical to A/South Australia/147/99 (H3N2) and was selected for this study. Two sera from children aged 4 and 3 years, respectively, and one adult (64 years old) were used to attempt selecting antigenic escape mutants. Virus was grown in MDCK cells in the presence of human serum and escaped variants were tested by haemagglutination-inhibition tests. Although variant strains were occasionally identified, their HA1 genetic sequence did not identify obvious changes at known antigenic sites. However, by cloning and subsequent sequencing, the genetic diversity of the parent virus was found to be significantly reduced when grown in the presence of human sera. Data also showed that the two children's sera selected additional mutants from those already present in the parent pool and that the two sera selected different mutants. On a community level, it is possible that antigenic changes could be accumulated in a step-wise manner when epidemic virus is transmitted from one small child to the next, each with a restricted and possibly variant antibody repertoire.
抗原变异株可能是在野外通过逃避群体免疫而产生的。我们之前发现，幼儿血清比成人血清更具毒株特异性，因此可能为选择抗原逃逸突变体提供有利条件。我们获得了1999/00流行季节后在挪威收集的少量匿名血清，该季节以A/巴拿马/2007/99（H3N2）变异株为主。该季节代表性毒株的血凝素（HA）基因与A/南澳大利亚/147/99（H3N2）在基因上相同，本研究选用了该毒株。分别使用两名4岁和3岁儿童以及一名64岁成人的血清来尝试选择抗原逃逸突变体。病毒在人血清存在的情况下在犬肾传代细胞（MDCK）中培养，逃逸变异株通过血凝抑制试验进行检测。虽然偶尔能鉴定出变异株，但其HA1基因序列在已知抗原位点未发现明显变化。然而，通过克隆及后续测序发现，在人血清存在的情况下培养时，亲代病毒的遗传多样性显著降低。数据还表明，两名儿童的血清从亲代病毒库中已有的毒株中筛选出了额外的突变体，且这两份血清筛选出的突变体不同。在社区层面，当流行病毒从一个幼儿传播到下一个幼儿时，抗原变化有可能以逐步的方式积累，每个幼儿都有受限且可能不同的抗体库。
