A systematic approach to simultaneously evaluate safety, immunogenicity, and efficacy of novel tuberculosis vaccination strategies
Muruganandah, Visai, Sathkumara, Harindra D., Pai, Saparna, Rush, Catherine M., Brosch, Roland, Waardenberg, Ashley J., and Kupz, Andreas (2020) A systematic approach to simultaneously evaluate safety, immunogenicity, and efficacy of novel tuberculosis vaccination strategies. Science Advances, 6 (10).
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Abstract
Tuberculosis (TB) is the deadliest infectious disease worldwide. Bacille-Calmette-Guerin (BCG), the only licensed TB vaccine, affords variable protection against TB but remains the gold standard. BCG improvement is focused around three strategies: recombinant BCG strains, heterologous routes of administration, and booster vaccination. It is currently unknown whether combining these strategies is beneficial. The preclinical evaluation for new TB vaccines is heavily skewed toward immunogenicity and efficacy; however, safety and efficacy are the dominant considerations in human use. To facilitate stage gating of TB vaccines, we developed a simple empirical model to systematically rank vaccination strategies by integrating multiple measurements of safety, immunogenicity, and efficacy. We assessed 24 vaccination regimens, composed of three BCG strains and eight combinations of delivery. The model presented here highlights that mucosal booster vaccination may cause adverse outcomes and provides a much needed strategy to evaluate and rank data obtained from TB vaccine studies using different routes, strains, or animal models.
| Item ID: | 62663 |
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| Item Type: | Article (Research - C1) |
| ISSN: | 2375-2548 |
| Related URLs: | |
| Copyright Information: | Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S.Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). |
| Additional Information: | A version of this publication was included as Appendix 1 of the following PhD thesis: Sathkumara, Harindra Darshana (2020) Mechanisms driving tuberculosis susceptibility and vaccine efficacy in HIV/AIDS and type 2 diabetes. PhD thesis, James Cook University, which is available Open Access in ResearchOnline@JCU. Please see the Related URLs for access. |
| Funders: | National Health and Medical Research Council (NHMRC) |
| Projects and Grants: | CJ Martin Biomedical Early Career Fellowship (APP1052764), Career Development Fellowship (APP1140709), New Investigator Project Grant (APP1120808) |
| Date Deposited: | 01 Apr 2020 07:32 |
| FoR Codes: | 31 BIOLOGICAL SCIENCES > 3107 Microbiology > 310702 Infectious agents @ 40% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320211 Infectious diseases @ 40% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320407 Innate immunity @ 20% |
| SEO Codes: | 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 65% 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 35% |
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