When estrogen deficiency meets immune responses induced by rabies vaccination

Estrogen deficiency in postmenopausal women is accompanied by immune status alterations, leading to a chronic low-grade inflammatory phenotype. Immediate rabies postexposure prophylaxis (PEP) following a transdermal bite or scratch from a rabies-infected animal is urgently needed. However, whether immune alterations in postmenopausal women influence the reaction to rabies vaccination remains unclear. Bilateral ovariectomized (OVX) and Sham mice were immunized with modified live vaccine RABV LBNSE. LBNSE immunization had no obvious pathological effect on the mice in either group and effectively protected all mice from RABV attack. Although 100% protection was found, the reduction rate of viral neutralizing antibody titers in the LBNSE-OVX mice was greater than that in the LBNSE-Sham mice. LBNSE immunization recruited/activated fewer dendritic cells (DCs) and B cells in the lymph nodes, while more B cells were detected in the blood of LBNSE-OVX mice than in that of LBNSE-Sham mice. Th1 and Th2 immune responses are both rapidly induced in LBNSE-OVX-subjected mice and are inclined toward a Th2-biased immune response. LBNSE immunization in OVX mice elicited similar amounts of RABV-specific CD4⁺ and CD8⁺ T cells as those in Sham mice. Our data revealed that the protective efficacy of rabies vaccination was slightly decreased by estrogen deficiency and that DC and B lymphocyte recruitment/activation and Th-mediated responses in splenocytes were partly altered; however, rabies vaccination offered sufficient protection against RABV within the observation period, helping alleviate anxiety related to rabies virus exposure after menopause. Additional measures might be helpful to improve long-term effective protection in postmenopausal women.IMPORTANCEMenopause has a distinct effect on the decrease in the female immune system, and whether protection efficacy after rabies vaccination in postmenopausal women is influenced requires evaluation. Our findings demonstrated that although viral neutralizing antibody (VNA) titers in the LBNSE-OVX mice were similar to those in the LBNSE-Sham mice, VNAs declined faster than those in the LBNSE-Sham mice within the observation period. Fewer dendritic cells in the lymph nodes were recruited/activated in LBNSE-OVX mice than in LBNSE-Sham mice, whereas B cells in the lymph nodes and peripheral blood exhibited the opposite tendency. Th2-biased immune responses were induced in LBNSE-OVX mice, and no significant changes were observed in RABV-specific CD4⁺ or CD8⁺ T cells. These results provide evidence that rabies vaccination could provide effective protection for postmenopausal women within the observation period, but other measures might be needed to improve protection, which is beneficial for alleviating anxiety of menopausal women when facing rabies immunization.