Non-specific effects of rabies vaccine on the incidence of common infectious disease episodes: study protocol for a randomized controlled trial

Darryn Knobel, Christianah Ibironke Odita, Anne Conan, Donna Barry, Marshalette Smith-Anthony, Juliet Battice, Shianne England, Bradford D Gessner, Darryn Knobel, Christianah Ibironke Odita, Anne Conan, Donna Barry, Marshalette Smith-Anthony, Juliet Battice, Shianne England, Bradford D Gessner

Abstract

Background: Vaccines may cause non-specific effects (NSEs) on morbidity and mortality through immune-mediated mechanisms that are not explained by the prevention of the targeted disease. Much of the evidence for NSEs comes from observational studies with a high risk of bias, and there is a clear need for new data from randomized controlled trials. Recently, it was proposed that rabies vaccine has protective NSEs in people and in animals. The aim of the proposed study is to determine whether rabies vaccine reduces the incidence rate of episodes of common infectious disease syndromes in a population of veterinary students on the island of St. Kitts.

Methods: The trial design is a single-site, two-arm, parallel-group, participant-blinded, randomized, placebo-controlled, two-sided comparative study, with an internal pilot study for blinded sample size re-estimation. Allocation to study arm is by block randomization stratified by sex within cohort with a 1:1 allocation ratio. The primary study outcome is the number of new weekly episodes of common infectious diseases including respiratory, diarrheal and febrile illnesses. A vaccine immunogenicity ancillary study is planned.

Discussion: Demonstration of a non-specific protective effect of rabies vaccine against unrelated respiratory, gastrointestinal and febrile illnesses would provide supportive evidence for the design of similar studies in children in populations with a high burden of these illnesses.

Trial registration: ClinicalTrials.gov, ID: NCT03656198. Registered on 24 August 2018.

Keywords: Diarrhea; Fever; Influenza-like illness; Non-specific effects of vaccines; Rabies vaccine; Upper respiratory disease.

Conflict of interest statement

BDG worked for Agence de Médecine Préventive (AMP) through 2017 and currently advises the company. AMP has received grant support from Sanofi Pasteur, a manufacturer of rabies vaccine. BDG currently serves as the Global Medical Lead for Pneumococcal Vaccines at Pfizer, but Pfizer has no role in the current study and Dr. Gessner participates in the current trial outside of his duties with Pfizer. The other authors declare that they have no competing interests.

Figures

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Fig. 1
Participant flow diagram

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Source: PubMed

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