Early Versus Delayed BCG Vaccination of HIV-exposed Infants

NCT ID: NCT02062580

Last Updated: 2017-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 149 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30

Brief Summary

In sub-Saharan Africa (SSA), more than 300,000 babies with HIV die each year. HIV-infected children develop AIDS and die faster in SSA than those in developed countries. Bacille Calmette-Guerin (BCG) vaccine is given to infants at birth in SSA to protect them from severe forms of TB. BCG is known to cause immune cells to be active and replicate faster. The immune system of neonates also responds differently to BCG that to other vaccines and infections. We hypothesize that the routine immunization of neonates with BCG contributes to generalized immune activation in HIV-exposed infants resulting in skewed immune responses to vaccines and infections and increased rates of disease progression in those infants that become HIV-infected. However, delaying BCG until HIV testing is completed would result in operational difficulties, and may not induce the appropriate immune response. Delayed BCG would also render many HIV-exposed uninfected infants at high risk for disseminated TB. We plan to assess immune cells in infants to determine the impact of the timing of BCG vaccination on immune responses to tuberculosis (TB) and other vaccines. We will also compare the immune activation and disease progression of those infants that become HIV-infected in the BCG or control arms. Our results will provide key insights into the effect of BCG vaccination on immune responses to HIV as well as inform the optimal timing of BCG vaccination for HIV-exposed infants.

Conditions

HIV Exposure; HIV Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Delayed BCG

BCG delayed to 8 weeks of age

Group Type: ACTIVE_COMPARATOR

BCG

Intervention Type: BIOLOGICAL

Early BCG

BCG at birth; standard of care

Group Type: OTHER

BCG

Intervention Type: BIOLOGICAL

Interventions

BCG

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Healthy neonate
• Maternal HIV
• > 36 weeks gestation
• Birth weight > 2.4kg
• Remaining in area 4 months

Exclusion Criteria

• Complications during pregnancy and delivery
• Household TB contacts

• Maximum Eligible Age: 24 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Seattle Children's Hospital

OTHER

Sponsor Role: collaborator

University of Stellenbosch

OTHER

Sponsor Role: collaborator

University of Cape Town

OTHER

Sponsor Role: lead

Responsible Party

Dr Heather Jaspan

Senior Lecturer

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Heather B Jaspan, MD, PHD

Role: PRINCIPAL_INVESTIGATOR

University of Cape Town

References

Gasper MA, Hesseling AC, Mohar I, Myer L, Azenkot T, Passmore JS, Hanekom W, Cotton MF, Crispe IN, Sodora DL, Jaspan HB. BCG vaccination induces HIV target cell activation in HIV-exposed infants in a randomized trial. JCI Insight. 2017 Apr 6;2(7):e91963. doi: 10.1172/jci.insight.91963.

Reference Type: DERIVED

PMID: 28405623 (View on PubMed)

Blakney AK, Tchakoute CT, Hesseling AC, Kidzeru EB, Jones CE, Passmore JA, Sodora DL, Gray CM, Jaspan HB. Delayed BCG vaccination results in minimal alterations in T cell immunogenicity of acellular pertussis and tetanus immunizations in HIV-exposed infants. Vaccine. 2015 Sep 11;33(38):4782-9. doi: 10.1016/j.vaccine.2015.07.096. Epub 2015 Aug 7.

Reference Type: DERIVED

PMID: 26259542 (View on PubMed)

Tchakoute CT, Hesseling AC, Kidzeru EB, Gamieldien H, Passmore JA, Jones CE, Gray CM, Sodora DL, Jaspan HB. Delaying BCG vaccination until 8 weeks of age results in robust BCG-specific T-cell responses in HIV-exposed infants. J Infect Dis. 2015 Feb 1;211(3):338-46. doi: 10.1093/infdis/jiu434. Epub 2014 Aug 8.

Reference Type: DERIVED

PMID: 25108027 (View on PubMed)

Other Identifiers

MV-00-9-900-01871

Identifier Type: -

Identifier Source: org_study_id