Evaluation of vaccine candidate potential of AaroA, AhtrA and AaroAAhtrA mutants of Salmonella enterica subspecies enterica serovar Abortusequi in guinea pigs

摘要

Salmonella enterica subspecies enterica serovar Abortusequi (S. Abortusequi), a host adapted Salmonella causes abortions, still births and foal mortality in equids. Though known since more than 100 years, it is still a problem in many of the developing countries including India. There is dearth of really good vaccine affording immunity lasting at least for one full gestation. In search of a potential vaccine candidate, three defined deletion mutants (AaroA, AhtrA and AaroAAhtrA) of S. Abortusequi were tested in guinea pig model for attenuation safety, immunogenicity, humoral immune response, protective efficacy and persistence in host. The AhtrA and AaroAAhtrA mutants were found to be safe on oral inoculation in doses as high as 4.2xl0~9 cfu/animal.Also through subcutaneous inoculation AaroAAhtrA mutant did not induce any abortion in pregnant guinea pigs. All the three mutants did not induce ajiy illness or death in 1-2 week-old baby guinea pigs except AhtrA mutant which caused mortality on intraperitoneal inoculation. Inoculation with mutants protected against challenge and increased breeding efficiency of guinea pigs. After >4.5 months of mutant inoculation, guinea pigs were protected against abortifacient dose of wild type S. Abortusequi and mother guinea pigs also conferred resistance to their babies to the similar challenge. Early humoral immune response of S. Abortusequi mutants was characteristic. Faecal excretion of AaroA and htrA mutants was detected up to 45 days of inoculation in guinea pigs while AaroAAhtrA mutant could not be detected after 21 days of inoculation. The results indicated that the double deletion mutant (AaroAAhtrA) was the most effective and safe candidate for vaccination against S. Abortusequi through mucosal routeof inoculation.