Mouse strain and sex as determinants of immune response to trivalent influenza vaccine

• Published in: Life sciences (1973) 2018-08, Vol.207, p.117-126
• Main Authors: Petrović, Raisa, Bufan, Biljana, Arsenović-Ranin, Nevena, Živković, Irena, Minić, Rajna, Radojević, Katarina, Leposavić, Gordana
• Format: Article
• Language: English
• Subjects: Antibodies; Antibody response; Antigens; Flow cytometry; Gender differences; Germinal center reaction; Hemagglutinins; Immune system; Immunization; Influenza; Influenza vaccine; Mouse genetic background; Rodents; Sex; Sex differences; Vaccines
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2018.05.056

The study examined the influence of sex and mouse strain on germinal center (GC) reaction and antibody responses to seasonal split trivalent influenza vaccine (TIV). C57BL/6 and BALB/c mice of both sexes were immunized with TIV and examined for specific antibody response by ELISA. Splenic T follicular regulatory (Tfr), T follicular helper (Tfh) and GC B cells are detected by flow cytometry. The proliferative response of splenocytes, and concentrations of IFN-γ and IL-4 upon restimulation with vaccine antigens were examined by 7-AAD staining and ELISA, respectively. BALB/c mice developed more robust IgG responses to vaccine type A antigens than their sex-matched C57BL/6 counterparts, while that to B antigen did not differ between strains. In both strains IgG responses against type A vaccine antigens were greater in females than in males. The greater IgG responses correlated with lower splenic Tfr/Tfh and Tfr/GC B cell ratios and greater vaccine antigen-specific proliferative responses of CD4+ and B cells in splenocyte cultures. In both mouse strains IgG2a(c)/IgG1 ratios were comparable between sexes, but lower in BALB/c than in C57BL/6 mice indicating a shift in Th1/Th2 balance towards Th2 response in BALB/c ones. Consistently, splenocytes from BALB/c mice produced more IL-4 and less IFN-γ than those from C57BL/6 mice. The study indicated that magnitude of humoral response to influenza type A haemagglutinins depends on mouse strain and sex, and thereby set background for the vaccination strategies taking into account biological sex, and in a longterm perspective individual differences in immune reactivity.