Clinical trial NCT02062580: Early Versus Delayed BCG Vaccination of HIV-exposed Infants
Official title: Influence of BCG Immunization on Immune Responses and Disease Progression in South African HIV Exposed and Infected Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Exposure
HIV Infection
Keywords: Vaccine immunogenicity
Immune activation
Lead sponsor: University of Cape Town
Sponsor class: OTHER
Collaborators: name: Seattle Children's Hospital
name: University of Stellenbosch
First posted: 2014-02-13
Enrollment: 149
Sex: ALL
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: T Cell Activation
timeFrame: at 6 weeks
Secondary outcomes:
measure: Vaccine Immunogenicity
timeFrame: 6 weeks after BCG vaccination
Other outcomes:
Locations:
Study officials:
affiliation: University of Cape Town
name: Heather B Jaspan, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.