Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO; ex-V3SWG)
In recognition of the increasing importance of viral vectors for the development of new vaccines and the need to understand their associated safety issues, the Brighton Collaboration (BC) created the Viral Vector Vaccines Safety Working Group (V3SWG) in October 2008. V3SWG was renamed to Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) in July of 2020, so as to expand beyond just vaccines using viral vectors. BRAVATO has two major activities:
1. Developing harmonized guidelines for assessing/addressing potential safety issues of concern for vaccines as listed in Table 1 of this paper, and initially identified in the meeting report from a World Health Organization Informal Consultation on Characterization and Quality Aspect of Vaccines Based on Live Viral Vectors, WHO HQ, Geneva, 4-5 December, 2003.
2. Completing standardized templates with key considerations for a risk/benefit assessment on new vaccine candidates to: a) facilitate scientific discourse among key stakeholders by increasing the transparency and comparability of information; and b) provide a checklist like tool for managing potential complex risks.
The original V3WG and updated BRAVATO viral vector template collects information on the characteristics of: a) the wild type virus from which the vector is derived; b) the vector itself before incorporation of the foreign antigen; and c) the final vaccine in animals and humans, toxicology and potency, with an overall adverse effect and risk assessment.
The viral vector template has been used for the standardized risk-assessment of several new viral vector vaccines, including some targeting Ebola (1, 5, 6, 7, 14, 15). The WHO Global Advisory Committee on Vaccine Safety (GACVS) endorsed the use of the template for other new candidate Ebola vaccines “as it is a structured approach to vaccine safety” (16, 17).
In 2020, the development of vaccines for COVID-19 is occurring with unprecedented speed. The pace and volume of development make a deliberate and systematic approach that is accessible and understandable to a diversity of stakeholders all the more important. Several vaccine platforms other than viral vector are being used (e.g., nucleic acid, protein, inactivated and live-attenuated). The V3SWG has therefore developed new specific templates, and revised its name to BRAVATO given the broader remit. The GACVS (18), the Coalition for Epidemic Preparedness Innovations (CEPI), and other key stakeholders will use these templates to evaluate and communicate the benefit-risk of vaccines using these platforms.
Below are links to the latest versions of each template in two forms: 1) the full “publication version”, including all introductory text and formatted for publication; and 2) the shorter and more easily updatable “website version”, formatted for easy completion and with extraneous text removed. Templates under development will be added once completed.
- Viral vector vaccines template
- Publication version
- Website Version
- Template revisions
- This document provides a summary of the three major version changes.
- Version 1 to Version 2 translation document
- This document provides a list of the vector template changes between the original Version 1 template and most updated Version 2 template. Changes are listed by template section.
- Chinese Translation
- Protein subunit vaccines template
- Nucleic acid vaccines template
- Inactivated viral vaccines template
- Live-attenuated viral vaccines template
- Maternal immunization module (under development)
For efficiency and harmonization, persons completing the “Target Pathogen and Population” section of BRAVATO templates for vaccine candidates funded by CEPI have the option of adapting the information posted below by the SPEAC Team.
BRAVATO hopes that eventually all vaccine developers/researchers (especially those likely to be used in humans in the near future) will complete the relevant template and submit it to BRAVATO and BC (email@example.com) for peer review and potential eventual publication in Vaccine. Following this, to promote transparency, the template will be posted and maintained on the BC website for use/reference by various stakeholders. Furthermore, recognizing the rapid pace of new scientific developments in this domain (relative to case definitions for adverse events following immunization), these completed templates can be updated with the help of each vector vaccine “community.” The science and the evidence contained in each published template (see: “Relevant publications (Activity 2 – Templates)” below) is constantly evolving. If you have a suggestion for an edit, please provide it using the form found at the bottom of this page.
Individuals who are interested in joining BRAVATO or participating in affiliated activities are welcome to contact firstname.lastname@example.org for possible membership.
WHO mentions of the template:
Relevant publications (Activity 1 – Guidelines):
4. Robert T. Chen, Baevin Carbery, Lisa Mac, et al. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG). Vaccine. Volume 33, Issue 1, 2015, Pages 73-75, https://doi.org/10.1016/j.vaccine.2014.09.035
5. Bettina Klug, James S. Robertson, Richard C. Condit, et al. Adventitious agents and live viral vectored vaccines: Considerations for archiving samples of biological materials for retrospective analysis. Vaccine. Volume 34, Issue 51, 2016, Pages 6617-6625, https://doi.org/10.1016/j.vaccine.2016.02.015
6. Richard C. Condit, Anna-Lise Williamson, Rebecca Sheets, et al.
Unique safety issues associated with virus-vectored vaccines: Potential for and theoretical consequences of recombination with wild type virus strains. Vaccine. Volume 34, Issue 51, 2016, Pages 6610-6616, https://doi.org/10.1016/j.vaccine.2016.04.060
7. Sonali Kochhar, Jean-Louis Excler, Karin Bok, et al. Defining the interval for monitoring potential adverse events following immunization (AEFIs) after receipt of live viral vectored vaccines. Vaccine. Volume 37, Issue 38, 2019, Pages 5796-5802, https://doi.org/10.1016/j.vaccine.2018.08.085
Relevant publications (Activity 2 – Templates):
8. Thomas P. Monath, Stephen J. Seligman, James S. Robertson, et al. Live virus vaccines based on a yellow fever vaccine backbone: Standardized template with key considerations for a risk/benefit assessment. Vaccine. Volume 33, Issue 1, 2015, Pages 62-72, https://doi.org/10.1016/j.vaccine.2014.10.004
9. David K. Clarke, R. Michael Hendry, Vidisha Singh, et al. Live virus vaccines based on a vesicular stomatitis virus (VSV) backbone: Standardized template with key considerations for a risk/benefit assessment. Vaccine. Volume 34, Issue 51, 2016, Pages 6597-6609, https://doi.org/10.1016/j.vaccine.2016.06.071
10. Thomas P. Monath, Patricia E. Fast, Kayvon Modjarrad, et al. rVSVΔG-ZEBOV-GP (also designated V920) recombinant vesicular stomatitis virus pseudotyped with Ebola Zaire Glycoprotein: Standardized template with key considerations for a risk/benefit assessment. Vaccine: X. Volume 1, 2019, 100009, https://doi.org/10.1016/j.jvacx.2019.100
11. Denny Kim, James S. Robertson, Jean-Louis Excler, et al. The Brighton Collaboration standardized template for collection of key information for benefit-risk assessment of nucleic acid (RNA and DNA) vaccines. Vaccine. 2020 Jul 22;38(34):5556-5561. doi: 10.1016/j.vaccine.2020.06.017.
13. Sonali Kochhar, Denny Kim, Jean-Louis Excler, et al. The Brighton Collaboration standardized template for collection of key information for benefit-risk assessment of protein vaccines. Vaccine. 2020 Jul 31;38(35):5734-5739. doi: 10.1016/j.vaccine.2020.06.044
14. Sonali Kochhar, Jean-Louis Excler, Denny Kim, et al. The Brighton Collaboration standardized template for collection of key information for benefit-risk assessment of inactivated viral vaccines. Vaccine. 2020;S0264-410X(20)30944-0. doi:10.1016/j.vaccine.2020.07.028
15. Robert T Chen, Sonali Kochhar, Richard C. Condit. The Brighton Collaboration Standardized Templates for Collection of Key Information for Benefit-Risk Assessment of Vaccines by Technology (BRAVATO; formerly V3SWG). 2020. Vaccine. 2021. https://doi.org/10.1016/j.vaccine.2020.10.072
16. Richard C. Condit, Denny Kim, James S. Robertson, et al. The Brighton Collaboration standardized template for collection of key information for benefit-risk assessment of viral vector vaccines [published online ahead of print, 2020 Sep 6]. Vaccine. 2020;S0264-410X(20)31030-6. doi:10.1016/j.vaccine.2020.08.009
17. Marc Gurwith, Richard C. Condit, Jean-Louis Excler, et al. Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) standardized template for collection of key information for benefit-risk assessment of live-attenuated viral vaccines. Vaccine. 2020. ISSN 0264-410X. https://doi.org/10.1016/j.vaccine.2020.09.042
18. Volkmann A, Williamson AL, Weidenthaler H, Meyer TPH, Robertson JS, Excler JL, Condit RC, Evans E, Smith ER, Kim D, Chen RT; Brighton Collaboration Viral Vector Vaccines Safety Working Group V3SWG. The Brighton Collaboration standardized template for collection of key information for risk/benefit assessment of a Modified Vaccinia Ankara (MVA) vaccine platform. Vaccine. 2020 Oct 17:S0264-410X(20)31091-4. doi: 10.1016/j.vaccine.2020.08.050.
19. Custers J, Kim D, Leyssen M, Gurwith M, Tomaka F, Robertson J, Heijnen E, Condit R, Shukarev G, Heerwegh D, van Heesbeen R, Schuitemaker H, Douoguiha M, Evans E, Smith ER, Chen RT,. Vaccines based on replication incompetent Ad26 viral vectors: standardized template with key considerations for a risk/benefit assessment. Vaccine. 2021. https://doi.org/10.1016/j.vaccine.2020.09.018
20. Eldridge, J. H., Egan, M. A., Matassov, D., Hamm, S., Hermida, L., Chen, T., Tremblay, M., Sciotto-Brown, S., Xu, R., Dimitrov, A., Smith, E. R., Gurwith, M., Chen, R. T., & Benefit-Risk Assessment of VAccines by TechnolOgy Working Group BRAVATO, ex-V3SWG) (2021). A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for a soluble glycoprotein vaccine to prevent disease caused by Nipah or Hendra viruses. Vaccine, 39(38), 5436–5441. https://doi.org/10.1016/j.vaccine.2021.07.030