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Early versus late BCG vaccination in HIV-1-exposed infants in Uganda: study protocol for a randomized controlled
Victoria Nankabirwa1,2, James K Tumwine3, Olive Namugga4
1Department of Epidemiology and Biostatics, School of Public Health, College of Health Sciences, Makerere University, Kampala, Uganda. nankabirwav@gmail.com.
Insights
Bacillus Calmette-Guérin (BCG) vaccination timing impacts infant health. This study compares early vs. later BCG in HIV-exposed infants to optimize protection against infections and improve immune responses.
Area of Science:
- Immunology
- Pediatrics
- Infectious Diseases
Background:
- Bacillus Calmette-Guérin (BCG) vaccination may offer broader protection against childhood infections beyond tuberculosis (TB).
- The optimal timing of BCG vaccination is debated, particularly for HIV-1-exposed infants who may have impaired immunity.
- Existing research, primarily observational, shows conflicting results on BCG's nonspecific effects.
Purpose of the Study:
- To compare the effects of BCG vaccination at birth versus at 14 weeks of age in HIV-1-exposed infants.
- To assess the impact of BCG timing on severe illness and immune responses to various antigens.
- To inform optimal BCG vaccination strategies for vulnerable infant populations.
Main Methods:
- Individually randomized controlled trial involving 2200 HIV-1-exposed infants in Uganda.
- Intervention: BCG vaccination within 24 hours of birth.
- Comparator: BCG vaccination at 14 weeks of age.
Main Results:
- Co-primary outcomes include severe illness rates within 14 weeks and cytokine production (TNF, IL-1β, IL-6, IFN-γ) in response to antigens.
- Data collection and analysis are ongoing to determine significant differences between the two BCG timing groups.
Conclusions:
- Well-timed BCG vaccination holds potential for significant nonspecific benefits in HIV-1-exposed infants.
- This trial's findings will guide the development of evidence-based BCG vaccination schedules for this population.
Background:
Bacillus Calmette-Guérin (BCG) vaccination may have nonspecific effects, i.e., effects on childhood morbidity and mortality that go beyond its effect on the risk of childhood tuberculosis (TB). Though the available scientific literature is mostly from observational studies, and is fraught with controversy, BCG vaccination at birth may protect infants in high-mortality populations against serious infections other than TB. Yet, other studies indicate that giving BCG later in infancy may modify immune responses to non-TB antigens and potentially enhance immunity, potentially also against tuberculosis (TB). It is unclear whether BCG vaccination very early in life offers adequate protection against TB and other infections among HIV-1-exposed children because even those who remain uninfected with HIV-1 show signs of impaired immunocompetence early in infancy. This study will compare BCG vaccination at birth with BCG vaccination at 14 weeks of age in HIV-1-exposed infants.
Methods:
This is an individually randomized controlled trial in 2200 HIV-1-exposed infants. The intervention is BCG vaccination within 24 h of birth while the comparator is BCG given at 14 weeks of age. The study co-primary outcomes are severe illness in the first 14 weeks of life, and production of tumor necrosis factor, interleukin (IL)-1β, IL-6 and interferon-γ in response to mycobacterial and nonmycobacterial antigens. The study is being conducted in three health centers in Uganda.
Discussion:
A well-timed BCG vaccination could have important nonspecific effects in HIV-1-exposed infants. This trial could inform the development of appropriate timing of BCG vaccination for HIV-1-exposed infants.
Trial Registration:
ClinicalTrials.gov, identifier: NCT02606526 . Registered on 12 November 2015.
