Amount and avidity of serum antibodies against native glycoproteins and denatured virus after repeated influenza whole-virus vaccination
Amount and avidity of serum antibodies against native glycoproteins and denatured virus after repeated influenza whole-virus vaccination
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DOI：
10.1016/j.vaccine.2004.08.053
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发表时间：
2005-02-03
期刊：
影响因子：
5.5
通讯作者：
Air, GM
中科院分区：
文献类型：
--
作者：
Gulati, U;Kumari, K;Air, GM
流感疫苗保护作用的相关因素仍存在不确定性。为了确定血凝抑制（HI）滴度与血清抗体的特异性和亲合力之间的关系，我们分析了来自流感疫苗效力的纵向试验（1983-1987）的血清[Keitel WA，Cate TR，Couch RB，Huggins LL，Hess KR.流感病毒灭活疫苗5年内每年重复免疫的有效性。Vaccine 1997; 15（10）：1114-22]。我们用胎球蛋白捕获天然病毒颗粒，并分别测量相对抗体水平和抗体对天然糖蛋白和变性病毒蛋白的抗体的亲和力。大多数受试者预先存在抗A/维多利亚/75的抗体，尽管70%的受试者在接种疫苗后抗A/Philippines/82的抗体增加了2倍以上，但只有30%的受试者显示抗A/维多利亚/75的抗体增加，表明原始抗原sin不占优势。与天然抗原相比，未折叠抗原的抗体水平存在变化，但针对变性蛋白的抗体从未超过针对天然病毒的抗体。在某些情况下，亲合力增加而抗体浓度没有显著增加，这可能解释了为什么一些低HI滴度的疫苗接种者表现出足够的保护。我们发现，接种前HI滴度和接种后的增加之间的负相关性也被视为抗体直接测量时，但HI滴度和抗体对天然糖蛋白，无论是在数量或亲合力之间的关系不大。我们的检测方法也适用于不与胎球蛋白结合的流感病毒，可能有助于疫苗评价。(C)2004爱思唯尔有限公司保留所有权利。
There is still uncertainty on the correlates of protection by influenza vaccine. To determine the relationship between hemagglutination-inhibition (HI) titer and the specificity and avidity of serum antibodies, we analyzed serum from a longitudinal trial (1983-1987) of influenza vaccine efficacy [Keitel WA, Cate TR, Couch RB, Huggins LL, Hess KR. Efficacy of repeated annual immunization with inactivated influenza virus vaccines over a five year period. Vaccine 1997; 15(10):1114-22]. We captured native virus particles with fetuin and separately measured relative antibody levels and avidities of antibodies against native glycoproteins and antibodies against denatured viral proteins. Most subjects had pre-existing antibodies against A/Victoria/75 and, although 70% had >two-fold increased antibodies against A/Philippines/82 after vaccination, only 30% showed increased antibodies to A/Victoria/75 indicating no dominance of original antigenic sin. There was variation in the levels of antibodies to unfolded antigens compared to native, but antibodies against denatured proteins never exceeded those against native virus. In some cases, the avidity increased without a significant increase in antibody concentration, which might explain why some vaccinees with low HI titer demonstrate adequate protection. We found that the negative correlation between pre-vaccination HI titer and the increase after vaccination is also seen when antibodies are measured directly, but that there is little relationship between HI titer and antibodies against native glycoproteins, either in amount or avidity. Our assay, which has also been adapted for recent influenza viruses that do not bind to fetuin, may be useful for vaccine evaluation. (C) 2004 Elsevier Ltd. All rights reserved.