IFITM3 affects the level of antibody response after influenza vaccination

Lei, Na; Li, Yan; Sun, Qiang; Lü, Jian; Zhou, Jianfang; Li, Zi; Liu, Liqi; Guo, Jianhua; Qin, Kun; Wang, Haibin; Zhao, Jianhong; Li, Chong; Sun, Lingli; Wang, Dayang; Zhao, Zhendong; Shu, Yuelong

doi:10.1080/22221751.2020.1756696

Cited by 24 publications

(19 citation statements)

References 43 publications

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“…If functional differences between the examined IFITM3 haplotypes are shown to produce distinct profiles of COVID-19 progression in severe patients, then an improved understanding of the underlying mechanisms may allow more adequate or personalized treatment protocols. Last but not least important, is the need for investigating the examined variant implications in raising an effective immune response after future vaccination against SARS-CoV-2, as it was recently demonstrated that homozygote rs12252:GG, actually reduces the level of antibody response after influenza vaccination (Lei et al, 2020). It could be important to verify whether this also stands for the upcoming SARS-CoV-2 vaccines, and whether a reduced antibody response could be instead elicited in this case by the major allele (rs12252:A), as was suggested throughout our analysis regarding COVID-19 severity.…”

Section: Resultsmentioning

confidence: 99%

Peer Review #1 of "The frequency of combined IFITM3 haplotype involving the reference alleles of both rs12252 and rs34481144 is in line with COVID-19 standardized mortality ratio of ethnic groups in England (v0.1)"

Jin¹

2020

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Section: Resultsmentioning

confidence: 99%

Peer Review #1 of "The frequency of combined IFITM3 haplotype involving the reference alleles of both rs12252 and rs34481144 is in line with COVID-19 standardized mortality ratio of ethnic groups in England (v0.1)"

Jin¹

2020

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“…If functional differences between the examined IFITM3 haplotypes are shown to produce distinct profiles of COVID-19 progression in severe patients, then an improved understanding of the underlying mechanisms may allow more adequate or personalized treatment protocols. Last but not least important, is the need for investigation of the examined variant implications in raising an effective immune response after future vaccination against SARS-CoV-2, as it was recently demonstrated that homozygote rs12252:GG, specifically, is reducing the level of antibody response after influenza vaccination (Lei et al, 2020). It could be important to verify whether this also stands for the upcoming SARS-CoV-2 vaccines, or whether the effect could be the opposite; namely with the reference alleles to be associated with reduced antibody response, as was suggested throughout this analysis regarding COVID-19 severity.…”

Section: Resultsmentioning

confidence: 99%

The Frequency of Combined IFITM3 Haplotype Involving the Reference Alleles of Both rs12252 and rs34481144 is in Line with COVID-19 Standardized Mortality Ratio of Ethnic Groups in England

Nikoloudis¹,

Kountouras²,

Hiona³

2020

Preprint

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Evidence was brought forward in England and the USA that Black, Asian, Latino and Minority Ethnic people exhibit higher mortality risk from COVID-19 than White people. While socioeconomic factors were suggested to contribute to this trend, they arguably do not explain the range of the differences observed, allowing for possible genetic implications. Almost concurrently, the analysis of a cohort in Chinese COVID-19 patients proposed an association between the severity of the disease and the presence of the minor allele of rs12252 of the Interferon-induced transmembrane protein 3 (IFITM3) gene. This SNP, together with rs34481144, are the two most studied polymorphisms of IFITM3 and have been associated in the past with increased severity in Influenza, Dengue, Ebola, and HIV viruses. IFITM3 is an immune effector protein that is pivotal for the restriction of viral replication, but also for the regulation of cytokine production. Following up to these two developments in the ongoing SARS-CoV-2 pandemic, the present study investigates a possible association between the differences in mortality of ethnic groups in England and the combined haplotypes of rs12252 and rs34481144. The respective allele frequencies were collected for 26 populations from 1000 Genomes Project and subgroups were pooled wherever possible to create correspondences with ethnic groups in England. A significant correlation (r=0.9687, p= 0.0003) was observed between the reported Standardized Mortality Ratios and the frequency of the combined haplotype of both reference alleles, suggesting that the combination of reference alleles of the specific SNPs may be implicated in more severe outcomes of COVID-19. This study calls for further focus on the role of IFITM3 variants in the mechanism of cellular invasion of SARS-CoV-2, their impact in COVID-19 severity and their possible implications in vaccination efficacy.

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“…IFITM3 is a kind of ISG. Lei et al reported that the deletion of IFITM3 attenuated the antibody response to influenza vaccination (35). However, no association has been investigated between IQGAP2 and IFITM3.…”

Section: Discussionmentioning

confidence: 99%

Identification of Two Novel Candidate Genetic Variants Associated With the Responsiveness to Influenza Vaccination

et al. 2021

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BackgroundAnnual vaccination is the most effective prevention of influenza infection. Up to now, a series of studies have demonstrated the role of genetic variants in regulating the antibody response to influenza vaccine. However, among the Chinese population, the relationship between genetic factors and the responsiveness to influenza vaccination has not been clarified through genome-wide association study (GWAS).MethodA total of 1,968 healthy volunteers of Chinese descent were recruited and 1,582 of them were available for the subsequent two-stage analysis. In the discovery stage, according to our inclusion criteria, 123 of 1,582 subjects were selected as group 1 and received whole-genome sequencing to identify potential variants and genes. In the verification stage, 29 candidate variants identified by GWAS were selected for further validation in 481 subjects in group 2. Besides, we also analyzed nine variants from previously published reports in our study.ResultsMultivariate logistic regression analysis showed that compared with the TT genotype of ZBTB46 rs2281929, the TC + CC genotype was associated with a lower risk of low responsiveness to influenza vaccination adjusted for gender and age (Group 2: P = 7.75E-05, OR = 0.466, 95%CI = 0.319–0.680; Combined group: P = 1.18E-06, OR = 0.423, 95%CI = 0.299–0.599). In the combined group, IQGAP2 rs2455230 GC + CC genotype was correlated with a lower risk of low responsiveness to influenza vaccination compared with the GG genotype (P = 8.90E-04, OR = 0.535, 95%CI = 0.370–0.774), but the difference was not statistically significant in group 2 (P = 0.008). The antibody fold rises of subjects with ZBTB46 rs2281929 TT genotype against H1N1, H3N2,and B were all significantly lower than that of subjects with TC + CC genotype (P < 0.001). Compared with IQGAP2 rs2455230 GC + CC carriers, GG carriers had lower antibody fold rises to H1N1 (P = 0.001) and B (P = 0.032). The GG genotype of rs2455230 tended to be correlated with lower antibody fold rises (P = 0.096) against H3N2, but the difference was not statistically significant. No correlation was found between nine SNPs from previously published reports and the serological response to influenza vaccine in our study.ConclusionOur study identified two novel candidate missense variants, ZBTB46 rs2281929 and IQGAP2 rs2455230, were associated with the immune response to influenza vaccination among the Chinese population. Identifying these variants will provide more evidence for future research and improve the individualized influenza vaccination program.

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IFITM3 affects the level of antibody response after influenza vaccination

Cited by 24 publications

References 43 publications

Peer Review #1 of "The frequency of combined IFITM3 haplotype involving the reference alleles of both rs12252 and rs34481144 is in line with COVID-19 standardized mortality ratio of ethnic groups in England (v0.1)"

Peer Review #1 of "The frequency of combined IFITM3 haplotype involving the reference alleles of both rs12252 and rs34481144 is in line with COVID-19 standardized mortality ratio of ethnic groups in England (v0.1)"

The Frequency of Combined IFITM3 Haplotype Involving the Reference Alleles of Both rs12252 and rs34481144 is in Line with COVID-19 Standardized Mortality Ratio of Ethnic Groups in England

Identification of Two Novel Candidate Genetic Variants Associated With the Responsiveness to Influenza Vaccination

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