To identify BCG immune correlates of protection against TB in children
whose understanding is critical for TB vaccine development.
1. To determine whether the post-vaccination number, function
and/or antigenic repertoire of specific conventional CD4+ and
CD8+ T cells correlate with protection against TB
2. To determine whether the post-vaccination number and/or
function of specific regulatory CD4+ T cells correlate with
protection against TB
3. To determine whether the post-vaccination gene expression
and cytokine secretion profiles of whole blood, and of PBMC,
correlate with protection against TB.
There were no differences in plasma levels of interferon-gamma, a
cytokine commonly used to measure vaccination outcome, or any other
cytokine, between the TB protected and TB non-protected children.
However, when combinations of cytokines were evaluated, a model that
included fractalkine, interleukin 12p40 and epidermal growth factor,
correct discrimination in 82% of “protected” and “unprotected” infants
was possible. Combinations of cytokines from plasma from blood
incubated for 7 hours without antigen also allowed correct
discrimination between the 2 groups. The studies on correlates of
protective immunity from BCG have strengthened laboratories at SATVI
which has since been awarded several EDCTP grants for TB vaccine
studies and trials. This fellowship supported the return of Willem
Hanekom to the country to re-establish his research career in South
|Hatherill M, Hawkridge T, Whitelaw A, Tameris M, Mahomed H, Moyo S, Hanekom W, Hussey G. Isolation of Non-Tuberculous Mycobacteria in Children Investigated for Pulmonary Tuberculosis. PLoS ONE. 2006 Dec;1:e21
|Hanekom WA. The immune response to BCG vaccination of newborns. Ann N Y Acad Sci. 2005 Dec;1062:69-78
|Murray RA, Mansoor N, Harbacheuski R, Soler J, Davids V, Soares A, Hawkridge A, Hussey GD, Maecker H, Kaplan G, Hanekom WA. Bacillus Calmette Guerin vaccination of human newborns induces a specific, functional CD8+ T cell response. J Immunol. 2006 Oct 15;177(8):5647-51
|Hanekom WA, Abel B, Scriba TJ. Immunological protection against tuberculosis. S Afr Med J. 2007 Oct;97(10 Pt 2):973-7
|Hussey G, Hawkridge T, Hanekom W. Childhood tuberculosis: old and new vaccines. Paediatr Respir Rev. 2007 Jun;8(2):148-54
|Scriba TJ, Kalsdorf B, Abrahams D-A, Isaacs F, Hofmeister J, Black G, Hassan HY, Wilkinson RJ, Walzl G, Gelderbloem SG, Mahomed H, Hussey GD, Hanekom WA. Distinct, specific IL-17 and IL-22- producing CD4+ T cell subsets contribute to the human antimycobacterial immune response. J Immunol. 2008; 180:1962- 1970
|Beveridge NER, Fletcher HA, Hughes J, Pathan AA, Scriba TJ, Minassian A, Sander CR, Whelan KT, Dockrell HM, Hill A, Hanekom WA, McShane H. A comparison of IFNy detection methods used in tuberculosis vaccine trials. Tuberculos. November 2008;88(6):631-640.
|Hatherill M, Hawkridge T, Zar HJ, Whitelaw A, Tameris M, Workman L, Geiter L, Hanekom WA, Hussey G. Induced sputum or gastric lavage for community-based diagnosis of childhood pulmonary tuberculosis? Arch. Dis. Child. 2009;94;195-201; originally published online 1 Oct 2008.
|Soares AP, Scriba TJ, Joseph S, Harbacheuski R, Murray RA, Gelderbloem SJ, Hawkridge A, Hussey GD, Maecker H, Kaplan G, Hanekom WA. Bacille Calmette Guerin vaccination of human newborns induces T cells with complex cytokine and phenotypic profiles. J Immunol. 2008 Mar 1;180(5):3569-77
|Fletcher HA, Filali-Mouhim A, Nemes E, et al. Human newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control study. BMC Medicine. 2016;14:76. doi:10.1186/s12916-016-0617-3.