Laboratory of Population Genetics, Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh.
Laboratory of Population Genetics, Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh.
Vaccine. 2024 Aug 30;42(21):126157. doi: 10.1016/j.vaccine.2024.126157. Epub 2024 Jul 30.
IFN-γ is an immunological modulator influencing IgG isotype and concentration, which present a correlate of protection to evaluate vaccine efficacy. As transiently expressed, stable genetic and epigenetic signatures of the cytokine's expression may exist. This study investigates correlation between plasma IFN-γ and anti-SARS-CoV-2 IgG levels, seeking genetic polymorphisms and epigenetic variations within the IFN-γ gene proximal promoter. 200 COVID-19-vaccinated adults were classified into seropositive and seronegative groups based on plasma anti-SARS-CoV-2 IgG. Upon correlation analysis between anti-SARS-CoV-2 IgG and IFN-γ levels, IFN-γ gene proximal promoter region was subjected to nucleotide sequencing for two subsets: seronegative (21 < Days post-vaccination ≤180, n = 11) and seropositive (IgG > Q and Days post-vaccination >180, n = 24). Relative unmethylation of IFN-γ proximal promoter was assessed for the latter subset and its correlation with plasma IFN-γ and IgG levels was evaluated. A statistically significant positive correlation (r = 0.492, p = 0.018) was observed between IFN-γ and anti-SARS-CoV-2 IgG in the seropositive group with persistently high IgG titre (IgG > Q Days elapsed post-vaccination >180). A heterozygous 5'-UTR variant (rs776667149:C>T) identified in one seronegative individual revealed a potential impact on PKR-mediated translational attenuation of IFN-γ mRNA. No significant correlation was found between IFN-γ proximal promoter unmethylation and its plasma levels among HAR individuals with Days post-vaccination of either >180 (r = 0.14, p = 0.679) or < 180 (r = -0.062, p = 0.693). This study demonstrates an extent of humoral immunity against SARS-CoV-2 among COVID-19 vaccinated Bangladeshi population. This study suggests plasma IFN-γ may play a role in maintaining persistent anti-SARS-CoV-2 IgG levels, which warrants further investigation along with genetic and/or epigenetic basis to fully establish its protective nature in COVID-19 vaccination.
IFN-γ 是一种免疫调节剂，影响 IgG 同种型和浓度，这是评估疫苗效力的保护相关因素。作为瞬时表达，细胞因子表达的稳定遗传和表观遗传特征可能存在。本研究调查了血浆 IFN-γ 与抗 SARS-CoV-2 IgG 水平之间的相关性，同时研究了 IFN-γ 基因近端启动子内的遗传多态性和表观遗传变异。根据血浆抗 SARS-CoV-2 IgG 将 200 名 COVID-19 疫苗接种成年人分为血清阳性和血清阴性组。在抗 SARS-CoV-2 IgG 与 IFN-γ 水平之间进行相关性分析后，对 IFN-γ 基因近端启动子区域进行核苷酸测序，分为两个亚组：血清阴性（21 < 接种后第天≤180，n = 11）和血清阳性（IgG > Q 和接种后第天 >180，n = 24）。对后者亚组进行 IFN-γ 近端启动子的相对非甲基化评估，并评估其与血浆 IFN-γ 和 IgG 水平的相关性。在 IgG 持续高滴度（IgG > Q 天接种后> 180）的血清阳性组中，观察到 IFN-γ 与抗 SARS-CoV-2 IgG 之间存在统计学上显著的正相关（r = 0.492，p = 0.018）。在一个血清阴性个体中鉴定出的 5'-UTR 变体（rs776667149：C>T）可能会影响 PKR 介导的 IFN-γ mRNA 翻译衰减。在接种后第天> 180（r = 0.14，p = 0.679）或 < 180（r = -0.062，p = 0.693）的 HAR 个体中，IFN-γ 近端启动子非甲基化与其血浆水平之间未发现显著相关性。本研究证明了 COVID-19 疫苗接种的孟加拉国人群中 SARS-CoV-2 的体液免疫程度。本研究表明，血浆 IFN-γ 可能在维持持续的抗 SARS-CoV-2 IgG 水平中发挥作用，这需要进一步研究，同时研究遗传和/或表观遗传基础，以充分确定其在 COVID-19 疫苗接种中的保护作用。
