Human Leukocyte Antigens and Cellular Immune Responses to Anthrax Vaccine Adsorbed
Human Leukocyte Antigens and Cellular Immune Responses to Anthrax Vaccine Adsorbed
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DOI：
10.1128/iai.00269-13
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发表时间：
2013-07-01
影响因子：
3.1
通讯作者：
Poland, Gregory A.
中科院分区：
文献类型：
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作者：
Ovsyannikova, Inna G.;Pankratz, V. Shane;Poland, Gregory A.
疫苗诱导的免疫应答的个体间差异部分是由于人类白细胞抗原（HLA）和其他基因家族中的宿主遗传多态性。本研究检测了健康受试者接种吸附炭疽疫苗（AVA）后HLA基因型、单倍型和纯合性与保护性抗原（PA）特异性细胞免疫应答之间的相关性。虽然在单个HLA等位基因或单倍型与对AVA的可变淋巴细胞增殖（LP）反应之间观察到有限的关联，但纯合子分析支持“杂合子优势”的假设。任何HLA位点纯合的个体表现出的PA特异性LP显著低于所有8个位点杂合的受试者（中位刺激指数[SI]，1.84 vs 2.95，P = 0.009）。同样，我们发现，I类（HLA-A）和II类（HLA-DQA 1和HLA-DQB 1）的纯合性与LP的总体减少显着相关，而杂合性在这三个位点。具体而言，在这些基因座上纯合的个体具有显著低于HLA-A（中位数SI，1.48对2.13，P = 0.005）、HLA-DQA 1（中位数SI，1.75对2.11，P = 0.007）和HLA-DQB 1（中位数SI，1.48对2.13，P = 0.002）基因座杂合的受试者的PA特异性LP。最后，HLA基因座纯合性的增加（>= 4）与LP反应的降低（P < 0.001）呈剂量依赖性。需要进一步的研究来重现这些发现，并确定HLA杂合子个体是否比HLA纯合子个体对其他毒力因子（炭疽杆菌LF和EF）产生更强的细胞免疫应答。
Interindividual variations in vaccine-induced immune responses are in part due to host genetic polymorphisms in the human leukocyte antigen (HLA) and other gene families. This study examined associations between HLA genotypes, haplotypes, and homozygosity and protective antigen (PA)-specific cellular immune responses in healthy subjects following immunization with Anthrax Vaccine Adsorbed (AVA). While limited associations were observed between individual HLA alleles or haplotypes and variable lymphocyte proliferative (LP) responses to AVA, analyses of homozygosity supported the hypothesis of a "heterozygote advantage." Individuals who were homozygous for any HLA locus demonstrated significantly lower PA-specific LP than subjects who were heterozygous at all eight loci (median stimulation indices [SI], 1.84 versus 2.95, P = 0.009). Similarly, we found that class I (HLA-A) and class II (HLA-DQA1 and HLA-DQB1) homozygosity was significantly associated with an overall decrease in LP compared with heterozygosity at those three loci. Specifically, individuals who were homozygous at these loci had significantly lower PA-specific LP than subjects heterozygous for HLA-A (median SI, 1.48 versus 2.13, P = 0.005), HLA-DQA1 (median SI, 1.75 versus 2.11, P = 0.007), and HLA-DQB1 (median SI, 1.48 versus 2.13, P = 0.002) loci, respectively. Finally, homozygosity at an increasing number (>= 4) of HLA loci was significantly correlated with a reduction in LP response (P < 0.001) in a dose-dependent manner. Additional studies are needed to reproduce these findings and determine whether HLA-heterozygous individuals generate stronger cellular immune response to other virulence factors (Bacillus anthracis LF and EF) than HLA-homozygous subjects.