Ignite Creation Date:
2024-05-05 @ 11:53 AM
Last Modification Date:
2024-10-26 @ 9:15 AM
Study NCT ID:
NCT00168545
Status:
COMPLETED
Last Update Posted:
2011-09-22
First Post:
2005-09-09
Brief Title:
Immunology of Non-specific Effects of Vaccine
Sponsor:
Bandim Health Project
Organization:
Bandim Health Project
Study Overview
Official Title:
Non-specific Effects of Vaccines - In Search of the Immunological Background
Status:
COMPLETED
Status Verified Date:
2006-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
OBJECTIVES
General To investigate the immunological background for the non-specific effects of diphtheria-tetanus-pertussis DTP and measles vaccines on child mortality
Specific Examine the cytokine responses and possible association with morbidity in a study of DTP vaccinated children who will be randomised to receive a measles vaccine or no vaccine at 4½ months of age All children will receive a measles vaccine at 9 months of age
General To investigate the immunological background for the non-specific effects of diphtheria-tetanus-pertussis DTP and measles vaccines on child mortality
Specific Examine the cytokine responses and possible association with morbidity in a study of DTP vaccinated children who will be randomised to receive a measles vaccine or no vaccine at 4½ months of age All children will receive a measles vaccine at 9 months of age
Detailed Description:
Non-specific effects of vaccines The idea of vaccines having non-specific effects was first proposed in 1991 from a study in Senegal West Africa It was discovered that children receiving high-titre measles vaccine HT at 6 months of age had higher mortality than children who received the standard titre measles vaccine STD at 9 months of age The difference was found only for girls A study from Haiti confirmed the effect Since children vaccinated with HT had lower mortality than their equivalents who had not received any measles vaccine the difference in mortality between recipients of HT vaccine and STD vaccine was explained by a non-specific beneficial effect of the STD measles vaccine rather than a harmful effect of the HT vaccine The non-specific beneficial effect of STD measles vaccine on child mortality has been reconfirmed in many data-sets
Also the BCG vaccine is associated with striking effects on child mortality reducing mortality by about 50 Further among BCG vaccinated children having a BCG scar or a positive tuberculin reaction was associated with about 55 lower mortality in the following 12 months than among children who had a negative tuberculin reaction or who did not have a BCG scar
The effect of OPV is difficult to separate from the effects of BCG and DTP vaccines since OPV is normally given together with these vaccines There have though been some periods without DTP in Bissau due to global shortage of vaccines and we have compared the case fatality at the hospital for children who received only OPV and children who received both the prescribed OPV and DTP Children having received OPV had 3-fold lower mortality than children having received both vaccines Data from an OPV vaccination campaign that took place in Guinea-Bissau also suggested a non-specific beneficial effect for the recipients Further studies from Chile and the Soviet Union have suggested that OPV had a beneficial effect on mortality and morbidity
In contrast DTP HBV and inactivated polio vaccine IPV seem to exert a non-specific detrimental effect on child mortality although the findings on DTP were considered controversial by a recent review Current studies indicate that the negative effect of DTP may be neutralized by a subsequent measles vaccination It is striking that all the vaccines with a non-specific beneficial effect are live whereas the vaccines with an apparently harmful effect are killed Results from animal studies have shown that attenuated live vaccines tend to induce a Th1 response and offer better protection against severe disease than the corresponding inactivated vaccines which tend to induce a Th2 response So far very few studies have examined whether these effects differ between male and female animals One study reported that BCG-vaccinated female mice were better protected against malaria parasites than male mice 31 There is therefore an urgent need to conduct studies that can help uncover the immunology behind the non-specific effects
Sex-specific effects All epidemiological studies carried out so far confirms the observation that non-specific effects are sex-specific Live vaccines measles BCG OPV have a beneficial effect that is particularly good for girls whereas inactivated vaccines DTP HBV IPV have a negative effect for girls To date there are no immunological studies which have examined whether routine vaccines affect the immune system differently for boys and girls
We thus propose to study in a randomised controlled trial of measles vaccination taking place in Guinea-Bissau the immunology of non-specific effects of vaccination and their interaction with sex Specifically among children who have received the 3 recommended doses of DTP we will be able to compare the cytokine and antibody profiles of children who receive an early dose of measles vaccine at 4½ months of age with children who receive no additional vaccine at this age
Also the BCG vaccine is associated with striking effects on child mortality reducing mortality by about 50 Further among BCG vaccinated children having a BCG scar or a positive tuberculin reaction was associated with about 55 lower mortality in the following 12 months than among children who had a negative tuberculin reaction or who did not have a BCG scar
The effect of OPV is difficult to separate from the effects of BCG and DTP vaccines since OPV is normally given together with these vaccines There have though been some periods without DTP in Bissau due to global shortage of vaccines and we have compared the case fatality at the hospital for children who received only OPV and children who received both the prescribed OPV and DTP Children having received OPV had 3-fold lower mortality than children having received both vaccines Data from an OPV vaccination campaign that took place in Guinea-Bissau also suggested a non-specific beneficial effect for the recipients Further studies from Chile and the Soviet Union have suggested that OPV had a beneficial effect on mortality and morbidity
In contrast DTP HBV and inactivated polio vaccine IPV seem to exert a non-specific detrimental effect on child mortality although the findings on DTP were considered controversial by a recent review Current studies indicate that the negative effect of DTP may be neutralized by a subsequent measles vaccination It is striking that all the vaccines with a non-specific beneficial effect are live whereas the vaccines with an apparently harmful effect are killed Results from animal studies have shown that attenuated live vaccines tend to induce a Th1 response and offer better protection against severe disease than the corresponding inactivated vaccines which tend to induce a Th2 response So far very few studies have examined whether these effects differ between male and female animals One study reported that BCG-vaccinated female mice were better protected against malaria parasites than male mice 31 There is therefore an urgent need to conduct studies that can help uncover the immunology behind the non-specific effects
Sex-specific effects All epidemiological studies carried out so far confirms the observation that non-specific effects are sex-specific Live vaccines measles BCG OPV have a beneficial effect that is particularly good for girls whereas inactivated vaccines DTP HBV IPV have a negative effect for girls To date there are no immunological studies which have examined whether routine vaccines affect the immune system differently for boys and girls
We thus propose to study in a randomised controlled trial of measles vaccination taking place in Guinea-Bissau the immunology of non-specific effects of vaccination and their interaction with sex Specifically among children who have received the 3 recommended doses of DTP we will be able to compare the cytokine and antibody profiles of children who receive an early dose of measles vaccine at 4½ months of age with children who receive no additional vaccine at this age
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| LÆGEVIDENSKABENS FREMME-2623 | None | None | None |
| NOVO-2624 | None | None | None |