Search

Problem: HSV-2 infected more than 491 million people aged 15-49 world-wide in 2016. The morbidity associated with recurrent infections and the increased risk of HIV infection make this a major health problem. To date there is no effective vaccine. Because HSV-2 ascends to the dorsal route ganglion within 12-18 h of infection, an effective vaccine will need to elicit a strong local resident CD8+ T cell response to prevent the infection from becoming life-long., Method of Study: Using a mouse model we investigated the potential of oral immunization with a novel lipid adjuvant (Liporale TM ) followed by local vaginal application of an inflammatory agents to protect against primary HSV-2 infections., Results: Oral vaccination of mice with live-attenuated HSV-2 in Liporale followed by vaginal application of DNFB or CXCL9/10 led to recruitment of tissue-resident CD8 + memory cells into the genital epithelia. This prime and pull vaccination strategy provided complete protection against wild-type HSV-2 challenge and prevented viral dissemination to the spinal cords., Conclusions: Activation of mucosal immunity by oral immunization, combined with induction of transient local genital inflammation can recruit long-lived tissue resident CD8 + T cells into the genital epithelium, providing significant protection against primary HSV-2 infection., (© 2022 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Problem: Group B Streptococcus (GBS) is a common colonizer of the female genital tract at the time of pregnancy and has been associated with severe neonatal infections. Despite trials for GBS vaccines already being underway, the factors influencing vaginal GBS colonization and clearance are currently poorly understood., Method of Study: Within this study, we investigated the host immune responses to GBS infections in mice that affect GBS vaginal colonization and clearance. Cervicovaginal swabs were used to measure vaginal GBS persistence, and vaginal cytokine responses were measured using the BioPlex ® system. Lymphocytes isolated from spleens were stimulated with UV-killed GBS to examine systemic cellular responses. Additional in vitro cellular experiments using human vaginal epithelial cells were also performed, examining the effect pregnancy level hormones had on GBS adhesion, invasion, and cytokine responses., Results: We observed significant differences in the ability of GBS serotype V infections to persist, compared with GBS serotype Ia vaginal infections. Vaginal cytokine response examination identified temporal changes in cytokine production (IL10, IFNγ, IL6, IL1β, and TNFα) in relation to GBS serotype and clearance or colonization. Lymphocyte proliferation assays also revealed robust cellular immune responses to GBS vaginal infections irrespective of clearance or colonization. In vitro human cellular analyses also identified that vaginal epithelial cell line cytokine production was suppressed in the presence of hormones despite no alteration in adhesion/invasion., Conclusion: Here, we establish previously unknown, serotype specific, temporal immune responses which may be associated with vaginal GBS colonization or clearance in the female genital tract., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)