Živković Irena, Petrović Raisa, Arsenović-Ranin Nevena, Petrušić Vladimir, Minić Rajna, Bufan Biljana, Popović Olga, Leposavić Gordana
Immunology Research Centre "Branislav Janković", Institute of Virology, Vaccines and Sera "Torlak", Belgrade, Serbia.
Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Biologicals. 2018 Mar;52:18-24. doi: 10.1016/j.biologicals.2018.01.007. Epub 2018 Feb 14.
The study explored influence of biological sex on development of humoral immune response to seasonal trivalent whole inactivated virus (WIV) and split virus (SV) influenza vaccines in outbred Swiss mouse model. To this end, mice of both sexes were immunized with WIV (WIV mice) and SV vaccines (SV mice) and examined for specific antibody response. Irrespective of sex, total IgG and neutralizing antibody responses to distinct virus strains were weaker in SV than in WIV mice. In WIV mice of both sexes, irrespective of strain specificity, IgG isotype response was dominated by IgG2a antibodies, while in SV mice nearly equal representation of IgG2a and IgG1 antibodies was found. The analyses of sex differences showed higher titers of H1N1-specific and both H1N1- and H3N2-specific total IgG and neutralizing antibodies in female WIV and SV mice, respectively. Additionally, sexual dimorphism in IgG subclass profile depended on vaccine type. Specifically, compared with males, in females WIV shifted IgG2a/IgG1 antibody ratio towards IgG2a isotype on the account of weaker IgG1 response, whereas in SV mice, irrespective of virus strain, IgG2a and IgG1 isotypes were equally represented in both sexes. These findings indicate the vaccine type-dependent sex bias in antibody response to inactivated influenza vaccines.
该研究在远交系瑞士小鼠模型中探讨了生物性别对季节性三价全病毒灭活疫苗（WIV）和裂解病毒（SV）流感疫苗体液免疫反应发展的影响。为此，对雌雄小鼠分别用WIV（WIV小鼠）和SV疫苗（SV小鼠）进行免疫，并检测其特异性抗体反应。无论性别如何，SV小鼠对不同病毒株的总IgG和中和抗体反应均弱于WIV小鼠。在两性WIV小鼠中，无论毒株特异性如何，IgG同种型反应均以IgG2a抗体为主，而在SV小鼠中，IgG2a和IgG1抗体的比例几乎相等。性别差异分析显示，雌性WIV和SV小鼠中H1N1特异性以及H1N1和H3N2特异性总IgG和中和抗体的滴度分别更高。此外，IgG亚类谱中的性别二态性取决于疫苗类型。具体而言，与雄性相比，雌性WIV小鼠中由于IgG1反应较弱，IgG2a/IgG1抗体比例向IgG2a同种型偏移，而在SV小鼠中，无论病毒株如何，两性中IgG2a和IgG1同种型的比例相等。这些发现表明，在对灭活流感疫苗的抗体反应中存在疫苗类型依赖性的性别偏差。
