title: Persistence of the immune response induced by BCG vaccination.
abstract: BACKGROUND
  Although BCG vaccination is recommended in most countries of the world, little is known of the persistence of BCG-induced immune responses. As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination, evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective.
  
  
  METHODS
  A randomised control study of UK adolescents was carried out to investigate persistence of BCG immune responses. Adolescents were tested for interferon-gamma (IFN-gamma) response to Mycobacterium tuberculosis purified protein derivative (M.tb PPD) in a whole blood assay before, 3 months, 12 months (n = 148) and 3 years (n = 19) after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination (n = 16).
  
  
  RESULTS
  A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination, but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees. Some individuals (11/86; 13%) failed to make a detectable antigen-specific response three months after vaccination, or lost the response after 1 (11/86; 13%) or 3 (3/19; 16%) years. IFN-gamma response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months. A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 (81%) made a detectable IFN-gamma response to M.tb PPD 14 years after infant vaccination as compared to 6/16 (38%) matched unvaccinated controls (p = 0.012); teenagers vaccinated in infancy were 19 times more likely to make an IFN-gamma response of > 500 pg/ml than unvaccinated teenagers.
  
  
  CONCLUSIONS
  BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the majority of vaccinees, although the magnitude of the peripheral blood response wanes from 3 months to 12 months and from 12 months to 3 years post vaccination. The data presented here suggest that because of such waning in the response there may be scope for boosting anti-tuberculous immunity in BCG vaccinated children anytime from 3 months post-vaccination. This supports the prime boost strategies being employed for some new TB vaccines currently under development.
authors.affiliation: London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. drw@gn.apc.org
authors.forename: Rosemary E
authors.initials: RE
authors.lastname: Weir
authors.forename: Patricia
authors.initials: P
authors.lastname: Gorak-Stolinska
authors.forename: Sian
authors.initials: S
authors.lastname: Floyd
authors.forename: Maeve K
authors.initials: MK
authors.lastname: Lalor
authors.forename: Sally
authors.initials: S
authors.lastname: Stenson
authors.forename: Keith
authors.initials: K
authors.lastname: Branson
authors.forename: Rose
authors.initials: R
authors.lastname: Blitz
authors.forename: Anne
authors.initials: A
authors.lastname: Ben-Smith
authors.forename: Paul E M
authors.initials: PE
authors.lastname: Fine
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Dockrell
mesh_terms: D000293:Adolescent; D001500:BCG Vaccine / Q000276:immunology*; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013997:Time Factors; D014376:Tuberculosis / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D006113:United Kingdom
chemical_list: D001500:BCG Vaccine; D007371:Interferon-gamma