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Sex-specific differences of humoral immunity and transcriptome diversification in older adults vaccinated with inactivated quadrivalent influenza vaccines.

ABSTRACT: Clinical data showed sex variability in the immune response to influenza vaccination, this study aimed to investigate differentially expressed genes (DEGs) that contribute to sex-bias immunity to quadrivalent inactivated influenza vaccines (QIVs) in the elderly. 60 healthy adults aged 60-80 yrs were vaccinated with QIVs, and gene expression was analyzed before and after vaccination. The humoral immunity was analyzed by HAI assay, and the correlation of gene expression patterns of two sex groups with humoral immunity was analyzed. The DEGs involved in type I interferon signaling pathway and complement activation of classical pathway were upregulated within 3 days in females. At Day 28, the immune response showed a male-bias pattern associated with the regulation of protein processing and complement activation of classical pathway. A list of DEGs associated with variant responses to influenza vaccination between females and males were identified by biology-driven clustering. Old females have a greater immune response to QIVs but a rapid antibody decline, while old males have the advantages to sustain a durable response. In addition, we identified genes that may contribute to the sex variations toward influenza vaccination in the aged. Our findings highlight the importance of developing personalized seasonal influenza vaccines.

SUBMITTER: Yang J

PROVIDER: S-EPMC8064175 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Influenza B virus (FLUBV) is a major respiratory pathogen of humans. Seasonal influenza vaccines include either one or both FLUBV lineage strains, Victoria, and Yamagata. Vaccine mismatch occurs frequently, particularly in countries where vaccines contain only one of the lineages. We have previously described the safety and efficacy of modified live attenuated FLUBV vaccines based on either virus with rearranged genomes (FluB-RAM and FluB-RANS) or carrying a PB1 segment with a combination of temperature sensitive mutations and a C-terminal HA tag (FluB-att). We compared side by side the immunological responses in female and male DBA/2J mice vaccinated with either one of these vaccines and those with isogenic backgrounds encoding a chimeric HA segment carrying an N-terminal peptide encoding the IgA inducing peptide (IGIP). Recombinant viruses with or without the IGIP modification were genetically stable over multiple passages in eggs. In mice, introduction of IGIP improved attenuation of the vaccine candidates, particularly for the FluB-RAM/IGIP compared with the non-IGIP FluB-RAM counterpart. In a prime-boost regime, mice were completely protected against lethal challenge with a homologous FLUBV strain. Recombinant viruses induced antibodies against HA considered of protective value. Antibodies against NA and NP were readily detected. Compared to male mice and regardless of the vaccine used, female mice showed a clear trend towards enhanced humoral and cross-reactive IgG and IgA anti-HA responses as well as against NA and NP. The presence of IGIP in the vaccine resulted in an overall trend towards reduced anti-HA responses but enhanced anti-NA and anti-NP responses, particularly of the IgA isotype. Mucosal and serological responses two weeks after challenge showed similar trends with clear differences observed based on sex, vaccine backbone, and whether the vaccine carried the IGIP modification. These findings are significant for the development of universal influenza vaccines.

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Sex-specific differences of humoral immunity and transcriptome diversification in older adults vaccinated with inactivated quadrivalent influenza vaccines.

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