Vaccines work by stimulating the body to produce a high-quality, rapid and specific immune response upon exposure to infection by a particular disease-causing microorganism - the microorganism targeted by the vaccine. Evidence is emerging that some vaccines may have additional 'non-specific effects' (NSEs); that is, effects on the immune system beyond the direct protection against the diseases for which the vaccines were developed. It has been proposed that rabies vaccine has protective NSEs in people and animals, with receipt of rabies vaccine in children associated with a reduced risk of meningitis and cerebral malaria in one study, and a history of rabies vaccination in free-roaming dogs associated with increased survival rates in another study. Studies in mice have shown that prior rabies vaccination protects against bacterial sepsis. The biological mechanism of action of any such NSE of rabies vaccine is unknown. Other vaccines with reported protective NSEs (e.g. bacillus Calmette-Guerin vaccine against tuberculosis, a disease caused by Mycobacterium tuberculosis) have been show to reprogram the immune system, leading to enhanced protection against infection with disease-causing microorganisms unrelated to M. tuberculosis.

In this study, we will test the hypothesis that rabies vaccine has non-specific protective effects against common infectious disease (CID) syndromes (upper respiratory illness, diarrhea and fever) in a population of veterinary students. We will randomly assign previously-unvaccinated students who volunteer for the study to receive a primary course of three injections of rabies vaccine (experimental group) or an identical course of three injections of sterile water (control group). Participants will not know to which group they have been assigned. We will ask all participants to report episodes of illness through an online survey each week for 26 weeks, and will also record all clinically- and laboratory-confirmed cases of illness with CID syndromes. We hypothesize that rates of self-reported new episodes of CID illness over 26 weeks will be at least 25% lower in the experimental group, relative to the control group.

Inclusion Criteria:

A student registered at RUSVM, and in the Veterinary Preparatory (VP) program or the 1st or 5th semester of the Doctor of Veterinary Medicine (DVM) program

Exclusion Criteria:

A student registered at RUSVM and in the VP program or the 1st or 5th semester of the DVM program will be excluded from the study if s/he:

1. has previously received a dose of rabies vaccine, or
2. is intending to undertake activities during the course of participation in the study that would increase their risk category of rabies exposure above that of the U.S. population at large, as defined by the Advisory Committee on Immunization Practices (ACIP) for human rabies prevention, or
3. does not provide informed consent for participation, or
4. enrolls in the study but does not present for the first injection within the first 12 weeks of the semester (up to and including Week 12), or
5. has a contraindication to rabies vaccine as described in the Rabivax-S package insert

Participants will be blinded to their study arm allocation. The intervention procedure will be identical for both arms (intramuscular injections at Student Health Services on days 0, 7 and 21). Participants allocated to the control group will receive an intramuscular injection of sterile water for injection using identical syringes and needles as for the vaccine group. The injection will be prepared in a separate room to maintain participant blinding.