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A phase 1b randomized study of the safety and immunological responses to vaccination with H4:IC31, H56:IC31, and BCG revaccination in Mycobacterium tuberculosis-uninfected adolescents in Cape Town, South Africa.

Publication ,  Journal Article
Bekker, L-G; Dintwe, O; Fiore-Gartland, A; Middelkoop, K; Hutter, J; Williams, A; Randhawa, AK; Ruhwald, M; Kromann, I; Andersen, PL; Tait, D ...
Published in: EClinicalMedicine
April 2020

Tuberculosis (TB) remains the leading cause of infectious disease-related death. Recently, a trial of BCG revaccination and vaccination with H4:IC31, a recombinant protein vaccine, in South African adolescents (Aeras C-040-404) showed efficacy in preventing sustained QuantiFERON (QFT) conversion, a proxy for Mycobacterium tuberculosis (M.tb) infection. A phase 1b trial of 84 South African adolescents was conducted, concurrent with Aeras C-040-404, to assess the safety and immunogenicity of H4:IC31, H56:IC31 and BCG revaccination, and to identify and optimize immune assays for identification of candidate correlates of protection in efficacy trials.Two doses of H4:IC31 and H56:IC31 vaccines were administered intramuscularly (IM) 56 days apart, and a single dose of BCG (2-8 × 105 CFU) was administered intradermally (ID). T-cell and antibody responses were measured using intracellular cytokine staining and binding antibody assays, respectively. Binding antibodies and CD4+/CD8+ T-cell responses to H4- and H56-matched antigens were measured in samples from all participants. The study was designed to characterize safety and immunogenicity and was not powered for group comparisons. (Clinicaltrials.gov NCT02378207).In total, 481 adolescents (mean age 13·9 years) were screened; 84 were enrolled (54% female). The vaccines were generally safe and well-tolerated, with no reported severe adverse events related to the study vaccines. H4:IC31 and H56:IC31 elicited CD4+ T cells recognizing vaccine-matched antigens and H4- and H56-specific IgG binding antibodies. The highest vaccine-induced CD4+ T-cell response rates were for those recognizing Ag85B in the H4:IC31 and H56:IC31 vaccinated groups. BCG revaccination elicited robust, polyfunctional BCG-specific CD4+ T cells, with no increase in H4- or H56-specific IgG binding antibodies. There were few antigen-specific CD8+ T-cell responses detected in any group.BCG revaccination administered as a single dose ID and both H4:IC31 and H56:IC31 administered as 2 doses IM had acceptable safety profiles in healthy, QFT-negative, previously BCG-vaccinated adolescents. Characterization of the assays and the immunogenicity of these vaccines may help to identify valuable markers of protection for upcoming immune correlates analyses of C-040-404 and future TB vaccine efficacy trials.NIAID and Aeras.

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Published In

EClinicalMedicine

DOI

EISSN

2589-5370

ISSN

2589-5370

Publication Date

April 2020

Volume

21

Start / End Page

100313

Related Subject Headings

  • 4206 Public health
  • 4203 Health services and systems
  • 3202 Clinical sciences
 

Citation

APA
Chicago
ICMJE
MLA
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Bekker, L.-G., Dintwe, O., Fiore-Gartland, A., Middelkoop, K., Hutter, J., Williams, A., … HVTN 602/Aeras A-042 Protocol Team. (2020). A phase 1b randomized study of the safety and immunological responses to vaccination with H4:IC31, H56:IC31, and BCG revaccination in Mycobacterium tuberculosis-uninfected adolescents in Cape Town, South Africa. EClinicalMedicine, 21, 100313. https://doi.org/10.1016/j.eclinm.2020.100313
Bekker, Linda-Gail, One Dintwe, Andrew Fiore-Gartland, Keren Middelkoop, Julia Hutter, Anthony Williams, April K. Randhawa, et al. “A phase 1b randomized study of the safety and immunological responses to vaccination with H4:IC31, H56:IC31, and BCG revaccination in Mycobacterium tuberculosis-uninfected adolescents in Cape Town, South Africa.EClinicalMedicine 21 (April 2020): 100313. https://doi.org/10.1016/j.eclinm.2020.100313.
Bekker L-G, Dintwe O, Fiore-Gartland A, Middelkoop K, Hutter J, Williams A, Randhawa AK, Ruhwald M, Kromann I, Andersen PL, DiazGranados CA, Rutkowski KT, Tait D, Miner MD, Andersen-Nissen E, De Rosa SC, Seaton KE, Tomaras GD, McElrath MJ, Ginsberg A, Kublin JG, HVTN 602/Aeras A-042 Protocol Team. A phase 1b randomized study of the safety and immunological responses to vaccination with H4:IC31, H56:IC31, and BCG revaccination in Mycobacterium tuberculosis-uninfected adolescents in Cape Town, South Africa. EClinicalMedicine. 2020 Apr;21:100313.
Journal cover image

Published In

EClinicalMedicine

DOI

EISSN

2589-5370

ISSN

2589-5370

Publication Date

April 2020

Volume

21

Start / End Page

100313

Related Subject Headings

  • 4206 Public health
  • 4203 Health services and systems
  • 3202 Clinical sciences