Herpes simplex virus 2 (HSV-2) infects more than 23 million people each year and can be fatal to the immunocompromised and newborns. Within 18 hours of initial exposure, HSV-2 establishes a lifelong infection by infecting the nerve endings in the genital tract. The speed of infection highlights the need for a vaccine to elicit an antibody and tissue resident memory cell response to protect the genital epithelia. Previous attempts using injected vaccines have not elicited the mucosal immunity necessary to prevent HSV-2 infection. Conversely, vaccines delivered by only mucosal routes (nasal, oral, vaginal and rectal) can elicit mucosal immunity and enhance protection against HSV-2. Vaccines must also be easy to administer for mass immunisation and stable enough to reach remote communities without the need for refrigeration. In this study, we developed an orally delivered vaccine that can maintain viability for long periods without refrigeration and reduced vaginal shedding of HSV-2.
HSV-2 was incorporated into adjuvant X and virus was stable for 3 months at 4oC, and for 2 weeks at room temperature and 37oC. Naïve mice were orally immunised four times with adjuvant X mixed with HSV-2. Capacity of mucosal antibodies generated following vaccination to neutralise HSV-2 was tested in vitro. Protection against external genital pathology (redness, swelling and ulceration) and HSV-2 vaginal shedding in immunised mice was determined by intravaginal challenge with HSV-2. Orally immunised mice had significantly reduced pathology and viral shedding in the genital tract compared to unimmunised controls. Protected mice had increased antibody levels in the serum and vaginal lavage that were able to neutralise more than 50% of HSV-2 in vitro. Our oral vaccine is resilient against interruptions in cold chain storage, is easily utilised to immunise mass populations and has the potential to protect against genital HSV-2 infection.