Esposito Martina, Minnai Francesca, Copetti Massimiliano, Miscio Giuseppe, Perna Rita, Piepoli Ada, De Vincentis Gabriella, Benvenuto Mario, D'Addetta Paola, Croci Susanna, Baldassarri Margherita, Bruttini Mirella, Fallerini Chiara, Brugnoni Raffaella, Cavalcante Paola, Baggi Fulvio, Corsini Elena Maria Grazia, Ciusani Emilio, Andreetta Francesca, Dragani Tommaso A, Fratelli Maddalena, Carella Massimo, Mantegazza Renato E, Renieri Alessandra, Colombo Francesca
National Research Council, Institute for Biomedical Technologies, Segrate, MI, Italy.
Department of Medical Biotechnology and Translational Medicine (BioMeTra), Università degli Studi di Milano, Milan, Italy.
Commun Med (Lond). 2024 Apr 4;4(1):63. doi: 10.1038/s43856-024-00490-2.
Since the beginning of the anti-COVID-19 vaccination campaign, it has become evident that vaccinated subjects exhibit considerable inter-individual variability in the response to the vaccine that could be partly explained by host genetic factors. A recent study reported that the immune response elicited by the Oxford-AstraZeneca vaccine in individuals from the United Kingdom was influenced by a specific allele of the human leukocyte antigen gene HLA-DQB1.
We carried out a genome-wide association study to investigate the genetic determinants of the antibody response to the Pfizer-BioNTech vaccine in an Italian cohort of 1351 subjects recruited in three centers. Linear regressions between normalized antibody levels and genotypes of more than 7 million variants was performed, using sex, age, centers, days between vaccination boost and serological test, and five principal components as covariates. We also analyzed the association between normalized antibody levels and 204 HLA alleles, with the same covariates as above.
Our study confirms the involvement of the HLA locus and shows significant associations with variants in HLA-A, HLA-DQA1, and HLA-DQB1 genes. In particular, the HLA-A*03:01 allele is the most significantly associated with serum levels of anti-SARS-CoV-2 antibodies. Other alleles, from both major histocompatibility complex class I and II are significantly associated with antibody levels.
These results support the hypothesis that HLA genes modulate the response to Pfizer-BioNTech vaccine and highlight the need for genetic studies in diverse populations and for functional studies aimed to elucidate the relationship between HLA-A*03:01 and CD8+ cell response upon Pfizer-BioNTech vaccination.
自新冠疫苗接种运动开始以来，很明显接种疫苗的个体对疫苗的反应存在相当大的个体差异，这部分可以由宿主遗传因素来解释。最近一项研究报告称，牛津-阿斯利康疫苗在英国个体中引发的免疫反应受人类白细胞抗原基因HLA-DQB1的一个特定等位基因影响。
我们开展了一项全基因组关联研究，以调查在意大利三个中心招募的1351名受试者组成的队列中，对辉瑞-BioNTech疫苗抗体反应的遗传决定因素。使用性别、年龄、中心、加强接种与血清学检测之间的天数以及五个主成分作为协变量，对超过700万个变异的标准化抗体水平与基因型进行线性回归分析。我们还分析了标准化抗体水平与204个HLA等位基因之间的关联，协变量与上述相同。
我们的研究证实了HLA基因座的参与，并显示与HLA-A、HLA-DQA1和HLA-DQB1基因中的变异存在显著关联。特别是，HLA-A*03:01等位基因与抗SARS-CoV-2抗体的血清水平最显著相关。来自主要组织相容性复合体I类和II类的其他等位基因也与抗体水平显著相关。
这些结果支持了HLA基因调节对辉瑞-BioNTech疫苗反应的假设，并强调了在不同人群中进行遗传研究以及开展旨在阐明HLA-A*03:01与辉瑞-BioNTech疫苗接种后CD8 +细胞反应之间关系的功能研究的必要性。
