Does neonatal BCG vaccination produce short and longer-term protection againstheterologous invasive infectious disease by enhancing the innate immune system? (360G-Wellcome-102915_Z_13_Z)

Bacillus-Calmette Guerin (BCG) vaccination at birth has been shown to reduce all-cause mortality in the neonatal period in low-birth-weight infants in a high-mortality setting. This is believed to occur due to broad protection against heterologous pathogens, but no biological mechanism has been elucidated. Epidemiological evidence suggests that this enhanced protection also occurs in term infants and persists long-term. This study will investigate short and longer-term alterations in the innate immune system response to non-mycobacterial pathogens induced by neonatal BCG vaccination. A single-blind, randomised controlled trial of BCG vaccination at birth vs. BCG vaccination at seven weeks of age will be conducted on 560 Ugandan infants. This will compare BCG vaccinated/unvaccinated infants until seven weeks of age and early/delayed BCG vaccination subsequently. The intervention groups will be compared shortly after vaccination and at distant time-points to assess differences in 1) innate cytokine levels following in-vitro stimulation with various pathogens and 2) inflammatory alterations in the hepcidin-iron axis. The potential for BCG-induced epigenetic modification of macrophages to produce long-term up-regulation of the innate immune response against heterologous pathogens will also be investigated. Discovery of a broadly protective effect of neonatal BCG vaccination would have profound implications for public healthcare policy.

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Grant Details

Amount Awarded 335043
Applicant Surname Prentice
Approval Committee PhD Studentships
Award Date 2013-08-30T00:00:00+00:00
Financial Year 2012/13
Grant Programme: Title PhD Training Fellowship for Clinicians
Internal ID 102915/Z/13/Z
Lead Applicant Dr Sarah Prentice
Partnership Value 335043
Planned Dates: End Date 2017-11-30T00:00:00+00:00
Planned Dates: Start Date 2013-09-30T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
Sponsor(s) Prof Alison Elliott, Prof David Mabey