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.