key: cord-0701985-f84u4u7t authors: Kochhar, Sonali; Excler, Jean-Louis; Kim, Denny; Robertson, James S.; Fast, Patricia E.; Condit, Richard C.; Drew, Stephen; Wood, David; Gurwith, Marc; Klug, Bettina; Whelan, Mike; Khuri-Bulos, Najwa; Mallett Moore, Tamala; Smith, Emily R.; Chen, Robert T. title: The Brighton Collaboration standardized template for collection of key information for benefit-risk assessment of inactivated viral vaccines date: 2020-09-03 journal: Vaccine DOI: 10.1016/j.vaccine.2020.07.028 sha: c3c3080a4601bbee91cc6c8d5fecf8d3b48507f5 doc_id: 701985 cord_uid: f84u4u7t Inactivated viral vaccines have long been used in humans for diseases of global health threat and are now among the vaccines for COVID-19 under development. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of inactivated viral vaccines. This will help key stakeholders to assess potential safety issues and understand the benefit-risk of the vaccine platform. The standardized and structured assessment provided by the template would also help to contribute to improved communication and support public acceptance of licensed inactivated viral vaccines. The Brighton Collaboration standardized template for collection of key information for benefit-risk assessment of inactivated viral vaccines Brighton Collaboration CEPI COVID-19 Vaccine Benefit-risk Safety Inactivated Virus Template a b s t r a c t Inactivated viral vaccines have long been used in humans for diseases of global health threat and are now among the vaccines for COVID-19 under development. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of inactivated viral vaccines. This will help key stakeholders to assess potential safety issues and understand the benefit-risk of the vaccine platform. The standardized and structured assessment provided by the template would also help to contribute to improved communication and support public acceptance of licensed inactivated viral vaccines. Ó 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). The Brighton Collaboration (www.brightoncollaboration.org) was launched in 2000 to improve the science of vaccine safety [1] . The Brighton Collaboration formed the Viral Vector Vaccines Safety Working Group (V3SWG) in October 2008 to improve the ability of key stakeholders to anticipate potential safety issues and meaningfully assess or interpret safety data, thereby facilitating greater public acceptance when viral vector vaccines are licensed [2] . One of the tools developed by the V3SWG is a standardized template describing the key considerations for benefitrisk assessment of viral vector vaccines. Completed by the vaccine developers/ sponsors, it will then be peer-reviewed by the V3SWG and published. The information in the template may facilitate communication of otherwise complex and highly technical data among key stakeholders and increase the transparency, comparability, and comprehension of essential information. The template has been used for the standardized risk assessment of several new viral Vaccine j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / v a c c i n e vector vaccines [3] [4] [5] , including some targeting Ebola. 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" [6] . In 2020, the development of vaccines for COVID-19 is occurring with unprecedented speed [7] . The pace and volume of vaccine development make a deliberate and systematic approach to safety that is accessible and understandable to a diversity of stakeholders of the utmost importance. Inactivated viral vaccine candidates are among the COVID-19 vaccines in development [8] . The Brighton Collaboration V3SWG has therefore developed a specific template for inactivated vaccines that the Coalition for Epidemic Preparedness Innovations (CEPI) and other key stakeholders could use to evaluate and communicate the benefit-risk assessment of using this platform. See Supplementary Material for definitions and additional guidance for completing this template. Inactivated viral vaccines have long been used in humans for diseases of global health threat, including poliomyelitis, pandemic and seasonal influenza, rabies, hepatitis A, Japanese encephalitis, tick borne encephalitis, and the technology of inactivation has more recently been used for emerging diseases such as West Nile, Chikungunya, Ross River and SARS [9, 10] . The vaccines can be whole inactivated virus or whole virus-derived subvirion vaccines [9] . The potential advantages of inactivated vaccines are that they cannot replicate in the host or revert to pathogenicity, and are nontransmissible [9] . Whole inactivated virus particles have the potential to induce a broad range of both humoral and cellular responses against all the different epitopes presented by the virus. However, due to the limited immunogenicity of some inactivated viral vaccines in humans, their development has also focused on methods to enhance the immune response, for example through the use of adjuvants, and optimizing the route or method of administration. Adjuvants are not usually licensed per se and it is the adjuvanted vaccine that is granted marketing authorization. Only a few different types of adjuvants are used in commercial vaccines while several others are under investigation. Whilst enhancing the immune response, adjuvants impart additional safety considerations to a vaccine that have to be carefully assessed [11] . The V3SWG intends that this template focuses on key questions related to the essential safety and benefit-risk issues relevant for the intrinsic properties of the vaccine components [12] . Although we recognize that other aspects of manufacturing, quality, and implementation can play an important role in the safety of a vaccine and vaccination, we have chosen to keep some of those issues out of scope in order to summarize the most useful information for stakeholders (see Table 1 ). The latest version of the template can be accessed on https:// brightoncollaboration.us/v3swg/. Vaccine developers are encouraged to complete the relevant templates for their vaccine candidate platform or vaccine candidate and collaborate with the V3SWG. The draft templates would be shared for review by the V3SWG and submitted for publication. Similarly, updates to the templates by the vaccine developers should be submitted to the Brighton Collaboration website for V3SWG review. Please read these instructions before you complete the ten sections. Send questions to:brightoncollaborationv3swg@gmail. com The first section entitled ''Authorship" should include your name and the latest date completing the form. If you are working with someone else to complete this form, their name should be provided as well. If you are updating the form, please provide the updated date. These co-authors will be included in the final published template in Vaccine once reviewed and approved by the V3SWG and in subsequent Wiki updates on the V3SWG website. Sections 2-8 collect information regarding the basic vaccine information (Section 2), the target pathogen and population (Section 3), characteristics of antigen (Section 4), inactivation method (Section 5), adjuvant (Section 6), delivery and administration (Section 7), toxicology and nonclinical (Section 8), and human efficacy and other important information (Section 9). Depending on the vaccine, some sections may be redundant or not applicable. In cases of redundancies, an answer may simply refer to the answer in a previous section. Answer questions by responding in the column entitled 'Information.' If you have any comments or concerns regarding the question or your answer to the question, note these in the 'Comments/Concerns' column. Finally, please provide references in the 'Reference' column. More than one reference can be used per question. You can simply write the first author's last name, first name initials, and year of publication (e.g., Lewis MH, 2003) in the ''Reference" column here, but please provide the full citation for the reference at the end of the form. Unpublished data are acceptable, though we do wish for you to include the source and contact information. Sections 10 and 11 have column titles that differ from preceding sections intended to provide a summary assessment of adverse effects and toxicity of the vaccine. Please summarize adverse effect and toxicities as requested and rate the risk in the following fashion: none, minimal, low, moderate, high, or unknown. If there is insufficient data for use of the platform in humans to accurately make these assessments, please state so in response to the questions. When completing information on adverse effects in Section 9, please provide as many details as possible based on the Brighton Collaboration Guidelines for collection, analysis and presentation of vaccine safety data in pre-and post-licensure clinical studies [13] . If a literature search was conducted to complete any of the Sections (strongly encouraged), please add the following information in the Reference(s) column: (1) time period covered (e.g., month/year to month/year); (2) Medical Subject Headings (MeSH) terms used; (3) the number of references found; and (4) the actual references with relevant information used. For prior published templates, please search PubMed for ''Brighton Collaboration V3SWG". The findings, opinions, conclusions, and assertions contained in this consensus document are those of the individual members of the Working Group. They do not necessarily represent the official positions of any participant's organization (e.g., government, university, or corporations) and should not be construed to represent any Agency determination or policy. We acknowledge the financial support provided by the Coalition for Epidemic Preparedness Innovations (CEPI) for our work under a service order entitled Safety Platform for Emergency vACcines (SPEAC) Project with the Brighton Collaboration, a program of the Task Force for Global Health, Decatur, GA. dDid it identify any safety issue of concern? dIf so describe: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The Brighton Collaboration: addressing the need for standardized case definitions of adverse events following immunization (AEFI) The Brighton collaboration viral vector vaccines safety working group (V3SWG) Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk/benefit assessment Live virus vaccines based on a vesicular stomatitis virus (VSV) backbone: Standardized template with key considerations for a risk/benefit assessment rVSVDG-ZEBOV-GP (also designated V920) recombinant vesicular stomatitis virus pseudotyped with Ebola Zaire Glycoprotein: Standardized template with key considerations for a risk/benefit assessment Global Advisory Committee on Vaccine Safety The COVID-19 vaccine development landscape World Health Organization. Draft landscape of COVID-19 candidate vaccines Vero cell technology for rapid development of inactivated whole virus vaccines for emerging viral diseases Inactivated virus vaccines from chemistry to prophylaxis: merits, risks and challenges Correlates of adjuvanticity: A review on adjuvants in licensed vaccines The Brighton Collaboration standardized templates for collection of key information for benefit-risk assessment of vaccines by technology (BRAVATO; formerly V3SWG). Vaccine Guidelines for collection, analysis and presentation of vaccine safety data in pre-and post-licensure clinical studies Rapid COVID-19 vaccine development We thank the following colleagues for their helpful advice: Marie-Helene Grillet, Stanley Plotkin, James Ackland, Hanneke Schuitemaker and Jerome Custers, Brighton Collaboration members. Other members of the V3SWG during the preparation of this document: George Pavlakis, Jonathan Smith, Karin Bok, and Merita Kucuku.