tetano
Editor, Senior Moderator
Emerg Microbes Infect. 2020 Apr 23:1-29. doi: 10.1080/22221751.2020.1756696. [Epub ahead of print]
IFITM3 Affects the Level of Antibody Response after Influenza Vaccination.
Lei N[SUP]1,[/SUP][SUP]2[/SUP], Li Y[SUP]1[/SUP], Sun Q[SUP]1,[/SUP][SUP]3[/SUP], Lu J[SUP]1[/SUP], Zhou J[SUP]1[/SUP], Li Z[SUP]1[/SUP], Liu L[SUP]1[/SUP], Guo J[SUP]1[/SUP], Qin K[SUP]1[/SUP], Wang H[SUP]2[/SUP], Zhao J[SUP]2[/SUP], Li C[SUP]2[/SUP], Sun L[SUP]2[/SUP], Wang D[SUP]1[/SUP], Zhao Z[SUP]4[/SUP], Shu Y[SUP]1,[/SUP][SUP]3[/SUP].
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Abstract
Interferon-induced transmembrane protein 3 (IFITM3) as an antiviral factor can inhibit replication of several viruses including influenza virus. A single-nucleotide polymorphism rs12252-C of IFITM3 results in a truncated IFITM3 protein lacking its first 21 amino acids, which is much higher in the Han Chinese population and associated with severe illness in adults infected with pandemic influenza H1N1/09 virus. To investigate if IFITM3 or IFITM3 rs12252-C could affect the antibody response after influenza vaccination, we detected the haemagglutination inhibition (HI) of 171 healthy young adult volunteers (IFITM3 rs12252-C/C, C/T, T/T carriers) and in an IFITM3-deletion mouse model (Ifitm3[SUP]-/-[/SUP]) after trivalent inactivated vaccine (TIV) immunization. Seroconversion rates for H1N1, H3N2 and B viruses in IFITM3 rs12252-C/C genotype carriers was lower compared with C/T and T/T donors. Significantly lower levels of specific antibodies to H1N1, H3N2 and B viruses and total IgG were observed in Ifitm3[SUP]-/-[/SUP] mice. Correspondingly, the numbers of splenic germinal center (GC) B cells, plasma cells, TIV-specific IgG[SUP]+[/SUP] antibody secreting cells and T follicular helper cells in Ifitm3[SUP]-/-[/SUP] mice were lower compared with wild type mice. However, the number of memory B cells was higher in Ifitm3[SUP]-/-[/SUP] mice at day 7 after booster. The HI level of Ifitm3[SUP]-/-[/SUP] mice remained lower than WT mice after third vaccination. Moreover, the transcriptional network regulating GC B cell and plasma cell differentiation was abnormal in Ifitm3[SUP]-/-[/SUP] mice. Our results indicate that IFITM3 deletion attenuated the antibody response. The mechanism of influenza-IFITM3 interactions affecting the antibody response requires further investigation.
KEYWORDS:
IFITM3; Immune response; Influenza virus; Interferon-induced transmembrane protein 3; SNP rs12252; Trivalent inactivated vaccine
PMID:32321380DOI:10.1080/22221751.2020.1756696
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IFITM3 Affects the Level of Antibody Response after Influenza Vaccination.
Lei N[SUP]1,[/SUP][SUP]2[/SUP], Li Y[SUP]1[/SUP], Sun Q[SUP]1,[/SUP][SUP]3[/SUP], Lu J[SUP]1[/SUP], Zhou J[SUP]1[/SUP], Li Z[SUP]1[/SUP], Liu L[SUP]1[/SUP], Guo J[SUP]1[/SUP], Qin K[SUP]1[/SUP], Wang H[SUP]2[/SUP], Zhao J[SUP]2[/SUP], Li C[SUP]2[/SUP], Sun L[SUP]2[/SUP], Wang D[SUP]1[/SUP], Zhao Z[SUP]4[/SUP], Shu Y[SUP]1,[/SUP][SUP]3[/SUP].
Author information
Abstract
Interferon-induced transmembrane protein 3 (IFITM3) as an antiviral factor can inhibit replication of several viruses including influenza virus. A single-nucleotide polymorphism rs12252-C of IFITM3 results in a truncated IFITM3 protein lacking its first 21 amino acids, which is much higher in the Han Chinese population and associated with severe illness in adults infected with pandemic influenza H1N1/09 virus. To investigate if IFITM3 or IFITM3 rs12252-C could affect the antibody response after influenza vaccination, we detected the haemagglutination inhibition (HI) of 171 healthy young adult volunteers (IFITM3 rs12252-C/C, C/T, T/T carriers) and in an IFITM3-deletion mouse model (Ifitm3[SUP]-/-[/SUP]) after trivalent inactivated vaccine (TIV) immunization. Seroconversion rates for H1N1, H3N2 and B viruses in IFITM3 rs12252-C/C genotype carriers was lower compared with C/T and T/T donors. Significantly lower levels of specific antibodies to H1N1, H3N2 and B viruses and total IgG were observed in Ifitm3[SUP]-/-[/SUP] mice. Correspondingly, the numbers of splenic germinal center (GC) B cells, plasma cells, TIV-specific IgG[SUP]+[/SUP] antibody secreting cells and T follicular helper cells in Ifitm3[SUP]-/-[/SUP] mice were lower compared with wild type mice. However, the number of memory B cells was higher in Ifitm3[SUP]-/-[/SUP] mice at day 7 after booster. The HI level of Ifitm3[SUP]-/-[/SUP] mice remained lower than WT mice after third vaccination. Moreover, the transcriptional network regulating GC B cell and plasma cell differentiation was abnormal in Ifitm3[SUP]-/-[/SUP] mice. Our results indicate that IFITM3 deletion attenuated the antibody response. The mechanism of influenza-IFITM3 interactions affecting the antibody response requires further investigation.
KEYWORDS:
IFITM3; Immune response; Influenza virus; Interferon-induced transmembrane protein 3; SNP rs12252; Trivalent inactivated vaccine
PMID:32321380DOI:10.1080/22221751.2020.1756696
Free full text