Primary oral vaccination followed by a vaginal pull protects mice against genital HSV‐2 infection

• Published in: American journal of reproductive immunology (1989) 2023-03, Vol.89 (3), p.e13668-n/a
• Main Authors: Mulvey, Peter B. M., Trim, Logan K., Aaskov, John G., Bryan, Emily R., Sweeney, Emma L., Kollipara, Avinash, Plenderleith, Mark B., Aldwell, Frank E., Beagley, Kenneth W.
• Format: Article
• Language: English
• Subjects: CD8 antigen; CD8-Positive T-Lymphocytes; Dinitrofluorobenzene; Epithelium; Female; herpes; Herpes Genitalis - prevention & control; Herpesvirus 2, Human; HIV; HIV Infections; Human immunodeficiency virus; Humans; Immunological memory; Infections; Inflammation; Lymphocytes T; Memory cells; Morbidity; Mucosal immunity; oral vaccination; prime and pull; Recurrent infection; tissue‐resident memory; Vaccination; Vaccines; Vagina
• ISSN: 1046-7408; 1600-0897
• DOI: 10.1111/aji.13668

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 (LiporaleTM) 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.