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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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Expression level of Cryptdine in intestine of vaccinated mice is not altered.RT-PCR showing expression level of Cryptdine in intestine of vaccinated; pregnant (Vacci-preg), non-pregnant (Vacci-N-preg) and non-vaccinated; pregnant (NonVacci-preg), non-pregnant (NonVacci-N-preg) mice (A). From each group of mice (Explained in material and methods) intestine was isolated and the RNA isolated using Trizol (SIGMA). RT-PCR was done and densitometric analysis for the expression levels of Cryptdine 1 (B), Cryptdine 4 (C and E) and Cryptdine 5 (D) as against β-actin used as internal control. Data shows that the various cryptdine levels are not down regulated after infection with DV-STM-07 and are similar to control.
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pone-0009139-g001: Expression level of Cryptdine in intestine of vaccinated mice is not altered.RT-PCR showing expression level of Cryptdine in intestine of vaccinated; pregnant (Vacci-preg), non-pregnant (Vacci-N-preg) and non-vaccinated; pregnant (NonVacci-preg), non-pregnant (NonVacci-N-preg) mice (A). From each group of mice (Explained in material and methods) intestine was isolated and the RNA isolated using Trizol (SIGMA). RT-PCR was done and densitometric analysis for the expression levels of Cryptdine 1 (B), Cryptdine 4 (C and E) and Cryptdine 5 (D) as against β-actin used as internal control. Data shows that the various cryptdine levels are not down regulated after infection with DV-STM-07 and are similar to control.

Mentions: The immune reaction against Salmonella involves both the innate and the adaptive immunity. A strong cell mediated immunity though protective can cause abortion by increasing the Th1 cytokines which can lead to fetal rejection. The protection offered by DV-STM-07 against challenge with WT Salmonella was surprising as this was achieved without inducing abortion. We suspected that the vaccine strain has a high degree of attenuation which does not elicit a strong inflammatory response but still is able to evoke a protective immune response. WT Salmonella is able to suppress the levels of antimicrobial peptide (AMP) cryptdine in the intestine which helps it to proliferate and spread [30]. AMPs are small cationic peptide with potent bactericidal activity. We looked at the level of cryptdine, in the vaccinated and unvaccinated mice. Small intestine was isolated and RNA was extracted. The RNA was reverse transcribed and semi-quantitative RT-PCR with mouse cryptdine 1, 4 and 5 specific primers was performed. We observed that vaccine strain did not down-regulate the different cryptdine levels as reported for WT Salmonella. Moreover, during pregnancy, the levels of all cryptdine tested were more in vaccinated pregnant mice compared to the control pregnant mice though not statistically significant (Figure 1A, B, C and D). The vaccine strain unlike the WT is unable to down regulate the levels of cryptdine ( Figure 1E). This may be one of the reasons why the vaccine strain is easily cleared from the host. Also the host cryptdine may induce lysis of bacteria leading to better antigen presentation.


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)

Expression level of Cryptdine in intestine of vaccinated mice is not altered.RT-PCR showing expression level of Cryptdine in intestine of vaccinated; pregnant (Vacci-preg), non-pregnant (Vacci-N-preg) and non-vaccinated; pregnant (NonVacci-preg), non-pregnant (NonVacci-N-preg) mice (A). From each group of mice (Explained in material and methods) intestine was isolated and the RNA isolated using Trizol (SIGMA). RT-PCR was done and densitometric analysis for the expression levels of Cryptdine 1 (B), Cryptdine 4 (C and E) and Cryptdine 5 (D) as against β-actin used as internal control. Data shows that the various cryptdine levels are not down regulated after infection with DV-STM-07 and are similar to control.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2818715&req=5

pone-0009139-g001: Expression level of Cryptdine in intestine of vaccinated mice is not altered.RT-PCR showing expression level of Cryptdine in intestine of vaccinated; pregnant (Vacci-preg), non-pregnant (Vacci-N-preg) and non-vaccinated; pregnant (NonVacci-preg), non-pregnant (NonVacci-N-preg) mice (A). From each group of mice (Explained in material and methods) intestine was isolated and the RNA isolated using Trizol (SIGMA). RT-PCR was done and densitometric analysis for the expression levels of Cryptdine 1 (B), Cryptdine 4 (C and E) and Cryptdine 5 (D) as against β-actin used as internal control. Data shows that the various cryptdine levels are not down regulated after infection with DV-STM-07 and are similar to control.
Mentions: The immune reaction against Salmonella involves both the innate and the adaptive immunity. A strong cell mediated immunity though protective can cause abortion by increasing the Th1 cytokines which can lead to fetal rejection. The protection offered by DV-STM-07 against challenge with WT Salmonella was surprising as this was achieved without inducing abortion. We suspected that the vaccine strain has a high degree of attenuation which does not elicit a strong inflammatory response but still is able to evoke a protective immune response. WT Salmonella is able to suppress the levels of antimicrobial peptide (AMP) cryptdine in the intestine which helps it to proliferate and spread [30]. AMPs are small cationic peptide with potent bactericidal activity. We looked at the level of cryptdine, in the vaccinated and unvaccinated mice. Small intestine was isolated and RNA was extracted. The RNA was reverse transcribed and semi-quantitative RT-PCR with mouse cryptdine 1, 4 and 5 specific primers was performed. We observed that vaccine strain did not down-regulate the different cryptdine levels as reported for WT Salmonella. Moreover, during pregnancy, the levels of all cryptdine tested were more in vaccinated pregnant mice compared to the control pregnant mice though not statistically significant (Figure 1A, B, C and D). The vaccine strain unlike the WT is unable to down regulate the levels of cryptdine ( Figure 1E). This may be one of the reasons why the vaccine strain is easily cleared from the host. Also the host cryptdine may induce lysis of bacteria leading to better antigen presentation.

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