Limits...
A safe vaccine (DV-STM-07) against Salmonella infection prevents abortion and confers protective immunity to the pregnant and new born mice.

Negi VD, Nagarajan AG, Chakravortty D - PLoS ONE (2010)

Bottom Line: The altered immune response of the pregnant female leads to increased susceptibility to invading pathogens, resulting in abortion and congenital defects of the fetus and a subnormal response to vaccination.These results suggest that our vaccine DV-STM-07 can be very useful in preventing abortion in the pregnant individuals and confer immunity to the new born.Since there are no such vaccine candidates which can be given to the new born and to the pregnant women, this vaccine holds a very bright future to combat Salmonella induced pregnancy loss.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Cell Biology, Centre for Infectious Disease Research and Biosafety Laboratories, Indian Institute of Science, Bangalore, India.

ABSTRACT
Pregnancy is a transient immuno-compromised condition which has evolved to avoid the immune rejection of the fetus by the maternal immune system. The altered immune response of the pregnant female leads to increased susceptibility to invading pathogens, resulting in abortion and congenital defects of the fetus and a subnormal response to vaccination. Active vaccination during pregnancy may lead to abortion induced by heightened cell mediated immune response. In this study, we have administered the highly attenuated vaccine strain DeltapmrG-HM-D (DV-STM-07) in female mice before the onset of pregnancy and followed the immune reaction against challenge with virulent S. Typhimurium in pregnant mice. Here we demonstrate that DV-STM-07 vaccine gives protection against Salmonella in pregnant mice and also prevents Salmonella induced abortion. This protection is conferred by directing the immune response towards Th2 activation and Th1 suppression. The low Th1 response prevents abortion. The use of live attenuated vaccine just before pregnancy carries the risk of transmission to the fetus. We have shown that this vaccine is safe as the vaccine strain is quickly eliminated from the mother and is not transmitted to the fetus. This vaccine also confers immunity to the new born mice of vaccinated mothers. Since there is no evidence of the vaccine candidate reaching the new born mice, we hypothesize that it may be due to trans-colostral transfer of protective anti-Salmonella antibodies. These results suggest that our vaccine DV-STM-07 can be very useful in preventing abortion in the pregnant individuals and confer immunity to the new born. Since there are no such vaccine candidates which can be given to the new born and to the pregnant women, this vaccine holds a very bright future to combat Salmonella induced pregnancy loss.

Show MeSH

Related in: MedlinePlus

Pre-pregnancy vaccination of mice reduces bacterial burden in pups.Non- pregnant nice were given 3 doses of 104 cfu of vaccine strain at an interval of one week. A week after the last vaccination the mice were mated. The pups of vaccinated and unvaccinated mice were challenged with 107 cfu of WT bacteria and on the 5th day of post infection of pups (4 weeks), organ CFU of Spleen and Liver (A) and PP and MLN (B) was recorded. Data shows the representative of three independent experiments performed. * p<0.05, ** p<0.001 (Mann-Whitney test).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2818715&req=5

pone-0009139-g003: Pre-pregnancy vaccination of mice reduces bacterial burden in pups.Non- pregnant nice were given 3 doses of 104 cfu of vaccine strain at an interval of one week. A week after the last vaccination the mice were mated. The pups of vaccinated and unvaccinated mice were challenged with 107 cfu of WT bacteria and on the 5th day of post infection of pups (4 weeks), organ CFU of Spleen and Liver (A) and PP and MLN (B) was recorded. Data shows the representative of three independent experiments performed. * p<0.05, ** p<0.001 (Mann-Whitney test).

Mentions: Transmissions of immunity to pups were assessed by measuring the levels of immunity of pups from vaccinated and unvaccinated mothers. The mother received 3 doses of vaccine strain before pregnancy (104 CFU/mice) or one dose (107) during pregnancy. PBS administered, uninfected mice were used as controls. After delivery, when 5–10 days old pups of WT infected mother were sacrificed and checked for organ CFU, very heavy load of bacteria was present in the liver, spleen, PP and MLN of the pup (Table 1). The remaining pups of all the groups were allowed to grow till 4–5 weeks of age and were infected with 107 CFU/mouse of WT Salmonella. We observed very high numbers of bacteria in the uninfected PBS control mother's pups and significantly less number of bacteria in the various organs like liver, spleen (Figure 2A), MLN and PP (Figure 2B) of the vaccinated mother's pups. WT infected mother's pups also showed less bacterial load (Figure 2A and B), which could be due to neonatal exposure of pups to Salmonella in WT infected mother. To show the vaccine strain is safe and is able to transmit immunity to pups even if administered before pregnancy, we conducted an experiment administering 3 doses of vaccination with 104 CFU per dose given before mating and the pregnancy outcome was recorded (Table 4). The pups of these vaccinated and unvaccinated mothers were challenged at 4 weeks of age with 107 WT bacteria per mouse. The pups were then sacrificed 5 days after challenge and their organs were plated to determine the bacterial load. The CFU in spleen, liver (Figure 3A), PP and MLN (Figure 3B) were lesser than the unvaccinated group. This was found to be statistically significant except in case of MLN. This suggests that immunity is being transferred to the next generation. The possible route of transmission of immunity can be through trans-placental transfer of anti-Salmonella IgG or through trans-colostral transfer of antibodies [31]. In another set of experiment the vaccinated and control mother were challenged with 107CFU/mouse of WT Salmonella and monitored for pregnancy outcome (Table 2).


A safe vaccine (DV-STM-07) against Salmonella infection prevents abortion and confers protective immunity to the pregnant and new born mice.

Negi VD, Nagarajan AG, Chakravortty D - PLoS ONE (2010)

Pre-pregnancy vaccination of mice reduces bacterial burden in pups.Non- pregnant nice were given 3 doses of 104 cfu of vaccine strain at an interval of one week. A week after the last vaccination the mice were mated. The pups of vaccinated and unvaccinated mice were challenged with 107 cfu of WT bacteria and on the 5th day of post infection of pups (4 weeks), organ CFU of Spleen and Liver (A) and PP and MLN (B) was recorded. Data shows the representative of three independent experiments performed. * p<0.05, ** p<0.001 (Mann-Whitney test).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2818715&req=5

pone-0009139-g003: Pre-pregnancy vaccination of mice reduces bacterial burden in pups.Non- pregnant nice were given 3 doses of 104 cfu of vaccine strain at an interval of one week. A week after the last vaccination the mice were mated. The pups of vaccinated and unvaccinated mice were challenged with 107 cfu of WT bacteria and on the 5th day of post infection of pups (4 weeks), organ CFU of Spleen and Liver (A) and PP and MLN (B) was recorded. Data shows the representative of three independent experiments performed. * p<0.05, ** p<0.001 (Mann-Whitney test).
Mentions: Transmissions of immunity to pups were assessed by measuring the levels of immunity of pups from vaccinated and unvaccinated mothers. The mother received 3 doses of vaccine strain before pregnancy (104 CFU/mice) or one dose (107) during pregnancy. PBS administered, uninfected mice were used as controls. After delivery, when 5–10 days old pups of WT infected mother were sacrificed and checked for organ CFU, very heavy load of bacteria was present in the liver, spleen, PP and MLN of the pup (Table 1). The remaining pups of all the groups were allowed to grow till 4–5 weeks of age and were infected with 107 CFU/mouse of WT Salmonella. We observed very high numbers of bacteria in the uninfected PBS control mother's pups and significantly less number of bacteria in the various organs like liver, spleen (Figure 2A), MLN and PP (Figure 2B) of the vaccinated mother's pups. WT infected mother's pups also showed less bacterial load (Figure 2A and B), which could be due to neonatal exposure of pups to Salmonella in WT infected mother. To show the vaccine strain is safe and is able to transmit immunity to pups even if administered before pregnancy, we conducted an experiment administering 3 doses of vaccination with 104 CFU per dose given before mating and the pregnancy outcome was recorded (Table 4). The pups of these vaccinated and unvaccinated mothers were challenged at 4 weeks of age with 107 WT bacteria per mouse. The pups were then sacrificed 5 days after challenge and their organs were plated to determine the bacterial load. The CFU in spleen, liver (Figure 3A), PP and MLN (Figure 3B) were lesser than the unvaccinated group. This was found to be statistically significant except in case of MLN. This suggests that immunity is being transferred to the next generation. The possible route of transmission of immunity can be through trans-placental transfer of anti-Salmonella IgG or through trans-colostral transfer of antibodies [31]. In another set of experiment the vaccinated and control mother were challenged with 107CFU/mouse of WT Salmonella and monitored for pregnancy outcome (Table 2).

Bottom Line: The altered immune response of the pregnant female leads to increased susceptibility to invading pathogens, resulting in abortion and congenital defects of the fetus and a subnormal response to vaccination.These results suggest that our vaccine DV-STM-07 can be very useful in preventing abortion in the pregnant individuals and confer immunity to the new born.Since there are no such vaccine candidates which can be given to the new born and to the pregnant women, this vaccine holds a very bright future to combat Salmonella induced pregnancy loss.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Cell Biology, Centre for Infectious Disease Research and Biosafety Laboratories, Indian Institute of Science, Bangalore, India.

ABSTRACT
Pregnancy is a transient immuno-compromised condition which has evolved to avoid the immune rejection of the fetus by the maternal immune system. The altered immune response of the pregnant female leads to increased susceptibility to invading pathogens, resulting in abortion and congenital defects of the fetus and a subnormal response to vaccination. Active vaccination during pregnancy may lead to abortion induced by heightened cell mediated immune response. In this study, we have administered the highly attenuated vaccine strain DeltapmrG-HM-D (DV-STM-07) in female mice before the onset of pregnancy and followed the immune reaction against challenge with virulent S. Typhimurium in pregnant mice. Here we demonstrate that DV-STM-07 vaccine gives protection against Salmonella in pregnant mice and also prevents Salmonella induced abortion. This protection is conferred by directing the immune response towards Th2 activation and Th1 suppression. The low Th1 response prevents abortion. The use of live attenuated vaccine just before pregnancy carries the risk of transmission to the fetus. We have shown that this vaccine is safe as the vaccine strain is quickly eliminated from the mother and is not transmitted to the fetus. This vaccine also confers immunity to the new born mice of vaccinated mothers. Since there is no evidence of the vaccine candidate reaching the new born mice, we hypothesize that it may be due to trans-colostral transfer of protective anti-Salmonella antibodies. These results suggest that our vaccine DV-STM-07 can be very useful in preventing abortion in the pregnant individuals and confer immunity to the new born. Since there are no such vaccine candidates which can be given to the new born and to the pregnant women, this vaccine holds a very bright future to combat Salmonella induced pregnancy loss.

Show MeSH
Related in: MedlinePlus