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Author Notes:

Correspondence and requests for materials should be addressed to S.B.S. (email: SSable@cdc.gov).

For authors' contributions and acknowledgements, see the full article.

Competing interests: SBS, RRA and BBP are co-inventors of a patent relating to anti-tuberculosis subunit vaccine consisting of Apa and other polypeptides which is being managed by CDC and US Department of Health and Human Services. Other authors have no competing financial interests.

Subjects:

Research Funding:

This work was supported by the Georgia Research Alliance collaboration grant (SBS, RRA, JEP and TM Shinnick), NIH/NIAID contract HHSN266200400091c (KD) and Centers for Disease Control and Prevention intramural funds.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • CD8(+) T-CELLS
  • IFN-GAMMA
  • BOVIS BCG
  • MICE
  • INFECTION
  • STRATEGY
  • EFFICACY
  • MUCOSAL
  • TH1
  • GLYCOPROTEIN
  • Protein vaccines
  • Tuberculosis

Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis

Tools:

Journal Title:

Scientific Reports

Volume:

Volume 6

Publisher:

, Pages 25837-25837

Type of Work:

Article | Final Publisher PDF

Abstract:

Heterologous prime-boosting has emerged as a powerful vaccination approach against tuberculosis. However, optimal timing to boost BCG-immunity using subunit vaccines remains unclear in clinical trials. Here, we followed the adhesin Apa-specific T-cell responses in BCG-primed mice and investigated its BCG-booster potential. The Apa-specific T-cell response peaked 32-52 weeks after parenteral or mucosal BCG-priming but waned significantly by 78 weeks. A subunit-Apa-boost during the contraction-phase of BCG-response had a greater effect on the magnitude and functional quality of specific cellular and humoral responses compared to a boost at the peak of BCG-response. The cellular response increased following mucosal BCG-prime-Apa-subunit-boost strategy compared to Apa-subunit-prime-BCG-boost approach. However, parenteral BCG-prime-Apa-subunit-boost by a homologous route was the most effective strategy in-terms of enhancing specific T-cell responses during waning in the lung and spleen. Two Apa-boosters markedly improved waning BCG-immunity and significantly reduced Mycobacterium tuberculosis burdens post-challenge. Our results highlight the challenges of optimization of prime-boost regimens in mice where BCG drives persistent immune-activation and suggest that boosting with a heterologous vaccine may be ideal once the specific persisting effector responses are contracted. Our results have important implications for design of prime-boost regimens against tuberculosis in humans.

Copyright information:

© 2016, Macmillan Publishers Limited.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).

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