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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.

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Th2 cytokine levels were higher in vaccinated than unvaccinated pregnant mice.Vaccinated and unvaccinated mice were sacrificed and checked for the cytokine profile. IL-4 was significantly more in vaccinated mice as compared to the unvaccinated mice (A) Levels of Serum IL-6 was enhanced in vaccinated mice but reverse was observed in case of the amniotic fluid of vaccinated and unvaccinated mice (B). Data shows the representative of three independent experiments performed. * p<0.05, ** p<0.001(Student “t” test).
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pone-0009139-g007: Th2 cytokine levels were higher in vaccinated than unvaccinated pregnant mice.Vaccinated and unvaccinated mice were sacrificed and checked for the cytokine profile. IL-4 was significantly more in vaccinated mice as compared to the unvaccinated mice (A) Levels of Serum IL-6 was enhanced in vaccinated mice but reverse was observed in case of the amniotic fluid of vaccinated and unvaccinated mice (B). Data shows the representative of three independent experiments performed. * p<0.05, ** p<0.001(Student “t” test).

Mentions: The cytokines regulating humoral immunity classified as Th2 cytokine, IL-4 signaling is very important for the development of plasma cells from pre B cells which is the most important step in the development of an effective humoral immunity. IL-4 also suppresses the development of Th1 mediated immune response. Hence, we checked the level of IL-4 secreted by the lymphocytes following vaccination. The splenocytes were isolated from vaccinated and unvaccinated pregnant mice and were maintained for 72 hrs in culture. The IL-4 levels were measured from the culture supernatants. Th2 cytokine IL-4 was increased almost by 2-folds in vaccinated pregnant mice (Figure 7A). We further analyzed the level of another Th2 cytokine IL-6, which plays a crucial role in immune regulation during pregnancy. Following vaccination, the IL-6 levels were determined in the serum of the mother and the amniotic fluid. IL-6 showed a contrasting profile in the serum and the amniotic fluid compartments. With vaccination, IL-6 level in the serum increased by 2-fold but the increase was not statistically significant. Level of IL-6 in amniotic fluid was 4-fold less in vaccinated pregnant mice as compared to the unvaccinated pregnant mice (Figure 7B). This drop is significant in preventing abortion, as IL-6 release stimulates prostaglandin synthesis by uterine tissues [32], [33]. The increase in the IL-4 and IL-6 levels in the maternal serum shows that the immune response has been biased towards the Th2 immune response. The drop in the IL-6 levels in the amniotic fluid also reveals that these levels do not follow the serum cytokine levels. But the overall change in the Th2 cytokine in maternal serum indicates the development of a fetus protecting cytokine milieu in the amniotic fluid compartment. Th2 serum cytokine profile also was not altered in the non-pregnant mice upon vaccination (Figure 6).


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)

Th2 cytokine levels were higher in vaccinated than unvaccinated pregnant mice.Vaccinated and unvaccinated mice were sacrificed and checked for the cytokine profile. IL-4 was significantly more in vaccinated mice as compared to the unvaccinated mice (A) Levels of Serum IL-6 was enhanced in vaccinated mice but reverse was observed in case of the amniotic fluid of vaccinated and unvaccinated mice (B). Data shows the representative of three independent experiments performed. * p<0.05, ** p<0.001(Student “t” test).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0009139-g007: Th2 cytokine levels were higher in vaccinated than unvaccinated pregnant mice.Vaccinated and unvaccinated mice were sacrificed and checked for the cytokine profile. IL-4 was significantly more in vaccinated mice as compared to the unvaccinated mice (A) Levels of Serum IL-6 was enhanced in vaccinated mice but reverse was observed in case of the amniotic fluid of vaccinated and unvaccinated mice (B). Data shows the representative of three independent experiments performed. * p<0.05, ** p<0.001(Student “t” test).
Mentions: The cytokines regulating humoral immunity classified as Th2 cytokine, IL-4 signaling is very important for the development of plasma cells from pre B cells which is the most important step in the development of an effective humoral immunity. IL-4 also suppresses the development of Th1 mediated immune response. Hence, we checked the level of IL-4 secreted by the lymphocytes following vaccination. The splenocytes were isolated from vaccinated and unvaccinated pregnant mice and were maintained for 72 hrs in culture. The IL-4 levels were measured from the culture supernatants. Th2 cytokine IL-4 was increased almost by 2-folds in vaccinated pregnant mice (Figure 7A). We further analyzed the level of another Th2 cytokine IL-6, which plays a crucial role in immune regulation during pregnancy. Following vaccination, the IL-6 levels were determined in the serum of the mother and the amniotic fluid. IL-6 showed a contrasting profile in the serum and the amniotic fluid compartments. With vaccination, IL-6 level in the serum increased by 2-fold but the increase was not statistically significant. Level of IL-6 in amniotic fluid was 4-fold less in vaccinated pregnant mice as compared to the unvaccinated pregnant mice (Figure 7B). This drop is significant in preventing abortion, as IL-6 release stimulates prostaglandin synthesis by uterine tissues [32], [33]. The increase in the IL-4 and IL-6 levels in the maternal serum shows that the immune response has been biased towards the Th2 immune response. The drop in the IL-6 levels in the amniotic fluid also reveals that these levels do not follow the serum cytokine levels. But the overall change in the Th2 cytokine in maternal serum indicates the development of a fetus protecting cytokine milieu in the amniotic fluid compartment. Th2 serum cytokine profile also was not altered in the non-pregnant mice upon vaccination (Figure 6).

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