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.
Safety Templates
Viral Vector Vaccines Template
This document provides a summary of the three major version changes.
This document provides a list of the vector template changes between the original Version 1 template and the most updated Version 2 template. Changes are listed by template section.
Access the translation of the Brighton Collaboration template for viral vector vaccines
Protein Subunit Vaccines Template
Nucleic Acid Vaccines Template
Inactivated Viral Vaccines Template
Live-attenuated Viral Vaccines Template
Modules
Maternal Immunization Module
Under development
Additional Resources
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.
WHO Mentions of BRAVATO Templates
Relevant Publications
Activity 1—Guidelines
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
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
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
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
Activity 2—Templates
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
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
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
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. https://doi.org/10.1016/j.vaccine.2020.06.017
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. https://doi.org/10.1016/j.vaccine.2020.06.044
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. https://doi.org/10.1016/j.vaccine.2020.07.028
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
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. https://doi.org/10.1016/j.vaccine.2020.08.009
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
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. https://doi.org/10.1016/j.vaccine.2020.08.050
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
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
Pedro M Folegatti, Daniel Jenkin, Susan Morris, Sarah Gilbert, Denny Kim, James S. Robertson, Emily R. Smith, Emalee Martin, Marc Gurwith, Robert T. Chen, Vaccines based on the replication-deficient simian adenoviral vector ChAdOx1: Standardized template with key considerations for a risk/benefit assessment, Vaccine, 2022, ISSN 0264-410X, https://doi.org/10.1016/j.vaccine.2022.06.008.
Libia Milena Hernandez, K. Sumathy, Sushant Sahastrabuddhe, Jean-Louis Excler, Sonali Kochhar, Emily R. Smith, Marc Gurwith, Robert T. Chen, A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for an inactivated viral vaccine against Chikungunya virus, Vaccine, 2022, ISSN 0264-410X, https://doi.org/10.1016/j.vaccine.2022.06.006
Brett Leav, Walter Straus, Phil White, Alison Leav, Tashawnee Gaines, Grace Maggiacomo, Denny Kim, Emily R. Smith, Marc Gurwith, Robert T. Chen, A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for the Moderna COVID-19 Vaccine (mRNA-1273), Vaccine, Volume 40, Issue 35, 2022, Pages 5275-5293, ISSN 0264-410X, https://doi.org/10.1016/j.vaccine.2022.06.005.
Wilkinson, B., Patel, K. S., Smith, K., Walker, R., Wang, C., Greene, A. M., Smith, G., Smith, E. R., Gurwith, M., Chen, R. T., & Benefit-Risk Assessment of VAccines by TechnolOgy Working Group BRAVATO; (ex-V3SWG) (2023). A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for the Novavax COVID-19 Vaccine (NVX-CoV2373), a recombinant spike protein vaccine with Matrix-M adjuvant to prevent disease caused by SARS-CoV-2 viruses. Vaccine, 41(45), 6762–6773. https://doi.org/10.1016/j.vaccine.2023.07.040.
Lila Estephan, Luke Tzu-Chi Liu, Chia En Lien, Emily R. Smith, Marc Gurwith, Robert T. Chen, A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for the Medigen COVID-19 protein vaccine, Vaccine, Volume 41, Issue 15, 2023, Pages 2615-2629, ISSN 0264-410X, https://doi.org/10.1016/j.vaccine.2023.02.083.
Shanti Pather, Nicola Charpentier, Frank van den Ouweland, Ruben Rizzi, Andrew Finlayson, Nadine Salisch, Alexander Muik, Claudia Lindemann, Ruzwana Khanim, Sultan Abduljawad, Emily R. Smith, Marc Gurwith, Robert T. Chen, A Brighton Collaboration standardized template with key considerations for a benefit-risk assessment for the Comirnaty COVID-19 mRNA vaccine, Vaccine, Volume 42, Issue 22, 2024, 126165, ISSN 0264-410X, https://doi.org/10.1016/j.vaccine.2024.126165.
