Intrauterine vaccination induces a dose-sensitive primary humoral response with limited evidence of recall potential.

PROBLEM: Induction of the local mucosal immune system within the reproductive tract is widely considered to be a key component in the development of effective prophylactic vaccines to control the spread of sexually transmitted infections. Here, we examine the capacity of the upper reproductive tract to act as a site of immune induction following. METHOD OF STUDY: Two vaccines formulated with a triple adjuvant combination and either recombinant bovine herpesvirus (tgD) protein or ovalbumin (OVA) were delivered at varying doses to the uterine lumen of rabbits and the resulting immune response evaluated after 32 days. RESULTS: Intrauterine vaccination produced a dose-dependent induction of both antigen-specific IgG and IgA in serum. Both uterine and broncheoalveolar lavage of the high and medium-dose vaccine group contained a significant increase in both anti-OVA and anti-tgD IgG, but no significant quantities of antigen-specific IgA were observed. The restimulation of splenocytes from the high-dose vaccine group with ovalbumin (OVA) only resulted in a small but significant increase in gene expression of the Th1 cytokines (IL2/IFNγ) in the absence of an observable increase in proliferation. CONCLUSION: Collectively, the results confirm the capacity of the uterine immune system to generate a primary response following stimulation.

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.