Effects of buprenorphine on immunogenicity and protective efficacy in the guinea pig keratoconjunctivitis model (Sereny test)

Shigellosis is a disease of global proportions, with an estimated 164.7 mil lion episodes annually throughout the world as well as an estimated 1.1 mil lion associated mortalities in developing countries. Due to increasing inci dence, and continued emergence of multi-drug resistant strains, Shigella va ccine development is considered a top public health priority. The guinea pi g keratoconjunctivitis model, the basis for the Sereny test, remains the mo st reliable in vivo indicator of virulence of Shigella strains and immunoge nicity and protective efficacy of Shigella vaccine candidates. The model is effective in evaluating the ability of Shigella strains to invade the corn eal epithelia of guinea pigs and spread to contiguous cells, with the more virulent strains causing ulcerative keratoconjunctivitis, However, analgesi a is not routinely used to relieve this painful condition because of potent ial immunomodulation and confounding of experimental results. The objective of the study reported here was to evaluate use of buprenorphine hydrochlor ide as an analgesic during the Sereny test, Local and systemic immune respo nses were measured in guinea pigs given buprenorphine versus those response s in controls. Results of this study suggest that buprenorphine, administer ed at an analgesic dose of 0.05 mg/kg of body weight twice daily, can be su ccessfully used with the model without significantly affecting immunologic evaluation of Shigella vaccine candidates. However, in buprenorphine-treate d animals, there was a significant increase in the amount of mucopurulent o cular discharge, requiring frequent cleaning of the affected eyes. Addition ally, animals treated with buprenorphine had significant reduction in body weight, in comparison with saline controls.