ABSTRACT
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 (deltaaroA, deltahtrA and deltaaroAdeltahtrA) of S. Abortusequi were tested in guinea pig model for attenuation, safety, immunogenicity, humoral immune response, protective efficacy and persistence in host. The deltahtrA and deltaaroAdeltahtrA mutants were found to be safe on oral inoculation in doses as high as 4.2 x 10(9) cfu/animal. Also through subcutaneous inoculation deltaaroAdeltahtrA mutant did not induce any abortion in pregnant guinea pigs. All the three mutants did not induce any illness or death in 1-2 week-old baby guinea pigs except deltahtrA 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 deltaaroA and htrA mutants was detected up to 45 days of inoculation in guinea pigs while deltaaroAdeltahtrA mutant could not be detected after 21 days of inoculation. The results indicated that the double deletion mutant (deltaaroAdeltahtrA) was the most effective and safe candidate for vaccination against S. Abortusequi through mucosal route of inoculation.
Subject(s)
Mutation , Salmonella Infections, Animal/prevention & control , Salmonella Vaccines/immunology , Salmonella enterica/genetics , Animals , Animals, Newborn , Antibody Formation , Female , Gene Deletion , Guinea Pigs , India , Male , Pregnancy , Pregnancy, Animal , Salmonella Infections, Animal/genetics , Salmonella Infections, Animal/immunology , Salmonella Vaccines/genetics , Time Factors , VaccinationABSTRACT
Erythrocyte deformability improves blood flow in the microvessels and in large arteries at high shear rate. The major determinants of RBC deformability include cell geometry, cell shape and internal viscosity (i.e., mean cell hemoglobin concentration and components of the erythrocyte membrane). The deformability is measured by several techniques but filtration of erythrocytes through micro-pore membranes and ektacytometry are two sensitive techniques to detect changes in erythrocytes under varied experimental and diseased conditions. Diabetes mellitus (DM) is a metabolic disorder, characterized by varying or persistent hyperglycemia, which induces several changes in the erythrocyte membrane and its cytoplasm, leading to alteration in the deformability. A decreasing trend of deformability in these patients is observed. The shape descriptor form factor, as determined by processing of erythrocyte images, increases with the increase of blood glucose levels and shows a pattern similar to filtration time of erythrocyte suspensions through cellulose membranes. Fluidity of the membrane as measured in erythrocytes of these patients is decreased. With prolonged diabetic conditions the deformability of erythrocytes is further decreased, which may complicate the flow of these cells in microvessels.