Establishment of a guinea pig model for evaluating the protective effects of new TB vaccines in BCG prime-boost regimen

Abstract

Objective To establish a suitable guinea pig model for evaluating the protective effects of new TB vaccines in BCG prime-boost regimen .Methods Two different immunization strategies by using the recombinant TB vaccine were employed to boost BCG primed guinea pigs in this study .One was for short-term evaluation with 14 weeks interval between prime and boost immunization and another was for long -term evaluation with 54 weeks interval .In the short-term evaluation group , guinea pigs were boosted twice with the recombinant TB vaccine （ AEC/BC02 ） in every two weeks , while guinea pigs in the long-term evaluation group were boosted for three times with two weeks interval between each injection .A negative con-trol group （ NS→NS） and a BCG control group （ BCG→NS） were both set up in two evaluation groups .One week after the last immunization , all guinea pigs were challenged with M.tuberculosis.Six to seven weeks after bacteria challenge , all animals were euthanized and dissected to evaluate lesion scores of liver , spleen and lung, as well as the viable bacterial load in spleen .Results In the short-term evaluation group , the le-sion scores in those boosted with vaccine （3.33±5.00） was lower than that of BCG control group （5.56± 7.27） （P〉0.05） and negative control group （47.00±28.11） （P=0.0001）.The difference between BCG control group and negative control group in lesion score was also significant .The animals in vaccine boosted group had lower bacterial loads （0.78±1.55 log10 ） in spleen than that in BCG control group （1.06±1.87） （P〉0.05） and negative control group （5.47±0.61） （P=0.0003）.In the long-term evaluation group, the lesion score in those boosted with vaccine was lower （5.0±7.6） than that in BCG control group （14.4± 13.5） （P=0.0394） and negative control group （56.9±14.1） （P〈0.0001）.The animals in vaccine boos-ted group （1.00±1.86 log10） had lower bacterial loads in spleen than that in BCG control group （1.46± 1.94） （P〉0.05） and negative control group （5.43±0.56） （P=0.01）.There was a significant difference in bacterial load between BCG control group and negative group （P=0.0089）.Conclusion The results suggest that the interval time between BCG-prime and boost immunization should be properly prolonged in the guinea pig model used for evaluating the protective effects of new TB vaccines in BCG prime -boost regimen . Key words: Tuberculosis; BCG-prime boost regimen; Animal model; Guinea pig; Recombinant TB vaccine