Intrauterine delivery of subunit vaccines induces a systemic and mucosal immune response in rabbits.
PROBLEM
Mucosal vaccines have long been sought after to improve protection though the production of both a mucosal and systemic immune response, and are thought to be particularly effective at the site of induction. Development of such vaccines has, however, been delayed by the general propensity to develop immune tolerance to antigens encountered at mucosal sites. This study aimed to determine whether an appropriately formulated subunit vaccine delivered to the uterine lumen would effectively trigger induction of immunity over tolerance.


METHODS
Ovalbumin (OVA), truncated glycoprotein D (tGD) from bovine herpesvirus, and a fusion protein of porcine parvovirus VP2 and bacterial thioredoxin (rVP2-TrX) were each formulated with a tri-adjuvant combination of Poly(I : C) (PIC), a host defense peptide (HDP), and a polyphosphazene (PCEP). A single dose of vaccine was delivered either intramuscularly (IM) or into the uterine lumen of intact female rabbits, and the humoral response subsequently evaluated both systemically and at local and distal mucosal sites.


RESULTS
Vaccination through either route-induced antigen-specific humoral responses systemically and within the local (uterus) and distal mucosa (lungs and vagina). The observed mucosal response was not compartmentalized to, or within, the upper genital tract and the degree of response appeared to be at least in part antigen dependant.


CONCLUSION
The results of this study provide proof of principle that the uterus can be used as an induction site for subunit vaccination and that vaccine formulation with appropriate adjuvants can trigger both systemic and mucosal immunity when administered IM or into the uterine lumen.
['Pasternak|Jonathan Alexander|JA|http://orcid.org/0000-0001-8596-3057', 'Hamonic|Glenn|G|', 'Forsberg|Nikki M|NM|', 'Wheler|Colette L|CL|', 'Dyck|Michael K|MK|', 'Wilson|Heather L|HL|']
D000276:Adjuvants, Immunologic D000818:Animals D000941:Antigens D002417:Cattle D005260:Female D006801:Humans D007108:Immune Tolerance D056724:Immunity, Humoral D018928:Immunity, Mucosal D011817:Rabbits D013552:Swine D014599:Uterus D014611:Vaccination D022223:Vaccines, Subunit
intrauterine subunit mucosal vaccine humoral reproductive tract