Table 1.

Brighton Collaboration Benefit-Risk Assessment of Vaccines by Technology (BRAVATO) Working Group Standardized Template v3.0 for Collection of Key Information for Risk Assessment of Viral Vaccine Vector Candidates. For the regular version, seehttps://brightoncollaboration.us/v3swg/.
	Part I: Viral Vector (2, 3)						Part II: Vaccine (Sections 8-12)
1. Authorship and Affiliation	2. Basic vector information	3. Characteristics of the wild type virus from which the vector is derived	4. Characteristics of the vector from which vaccine(s) may be derived	5. Toxicology and Potency (Pharmacology) of the Vector	6. Adverse Event (AE) Assessment of the Vector (*see Instructions):	7. Overall Risk Assessment of the Vector	8. Target Pathogen and Population for the vaccine	9. Characteristics of the Vaccine	10. Toxicology and Potency (Pharmacology) of the Vaccine	11. Adverse Event (AE) Assessment of the Vaccine (*see Instructions):	12. Overall Risk Assessment of the Vaccine	13. Any other information concerning either the viral vector or the vaccine
1.1. Author(s) and affiliation	2.1 Vector name	3.1 Name of wild type virus (common name; Family/Genus/ Species/subtype)	4.1 Describe the source of the vector (e.g. isolation, synthesis)	5.1. What is known about the replication,	6.1. Approximately how many humans have received any vaccine using this viral vector to date? If variants of the vector, please list separately.	7.1. Please summarize key safety issues of concern identified to date, if any:	8.1 What is the target pathogen for the vaccine?	9.1 Vaccine name	10.1. What is known about the replication,transmission and pathogenicity of the vaccine in and between animals?	11.1. Approximately how many humans have received this viral vector vaccine to date? If variants of the vector, please list separately	12.1. Please summarize key safety issues of concern identified to date, if any:
1.2.  Date completed/ updated	2.2. Vector origin Family/ Genus/ Species /subtype	3.2 What is the natural host for the wild type virus?	4.2. What is the basis of attenuation/inactivation of the wild type virus to create the vector?	transmission and pathogenicity of the vector in and between animals?	6.2. Method(s) used for safety monitoring:	● how should they be addressed going forward:	8.2 What are the disease manifestations caused by the target pathogen in humans, for the following categories:	9.2. What is the identity and source of the transgene?	10.2. For replicating vectors, has a comparative virulence and viral kinetic study been conducted in permissive and susceptible species? (yes/no) If not, what species would be used for such a study? Is it feasible to conduct such a study?	11.2. Method(s) used for safety monitoring:	● how should they be addressed going forward:
	2.3. Vector replication in humans (replicating or non-replicating)	3.3. How is the wild type virus normally transmitted?	4.3. What is known about the replication, transmission and pathogenicity of the vector in humans in the following categories:	5.2. For replicating vectors, has a comparative virulence and viral kinetic study been conducted in permissive and susceptible species? (yes/no) If not, what species would be used for such a study? Is it feasible to conduct such a study?	●  Spontaneous reports/passive surveillance	7.2. What is the potential for causing serious unwanted effects and toxicities in:	●  In healthy people	9.3. Is the transgene likely to induce immunity to all strains/genotypes of the target pathogen?	10.3. Does an animal model relevant to assess attenuation exist?	● Spontaneous reports/passive surveillance	12.2. What is the potential for causing serious unwanted effects and toxicities in:
		3.4. Does the wild type virus establish a latent or persistent infection?	● In healthy people	5.3. Does an animal model relevant to assess attenuation exist?	● Diary	●healthy humans?	● In immunocompromised people	9.4. Where in the vector genome is the transgene inserted?	10.4. Does an animal model for safety including immuno-compromised animals exist?	●Diary	●   healthy humans?
		3.5. Does the wild type virus replicate in the nucleus?	● In immunocompromised people	5.4. Does an animal model for safety including immuno-compromised animals exist?	● Other active surveillance	●immunocompromised humans?	● In neonates, infants, children	9.5. Does the insertion of the transgene involve deletion or other rearrangement of any vector genome sequences?	10.5. Does an animal model for reproductive toxicity exist?	●Other active surveillance	● immunocompromised humans?
		3.6. What is the risk of integration into the human genome?	● In breast milk, neonates, infants, children	5.5. Does an animal model for reproductive toxicity exist?	6.3. What criteria were used for grading the AE’s?	● Breast milk, human neonates, infants, children?	● During pregnancy and in the fetus	9.6. How is the transgene expression controlled (transcriptional promoters, etc.)?	10.6. Does an animal model for immunogenicity and efficacy exists?	11.3. What criteria were used for grading the AE’s?	● Breast milk, human neonates, infants, children?
		3.7. List any disease manifestations caused by the wild type virus, the strength of evidence, severity, and duration of disease for the following categories:	● during pregnancy and in the fetus	5.6. Does an animal model for immunogenicity and efficacy exists?	●  2007 US FDA Guidance for Industry Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials	● pregnancy and in the fetus in humans?	● In elderly	9.7. Does insertion or expression of the transgene affect the pathogenicity or phenotype of the vector?	10.7 Does an animal model for antibody enhanced disease (including antibody dependent enhancement (ADE), vaccine associated enhanced respiratory disease (VAERD)) or immune complex disease exist?	● 2007 US FDA Guidance for Industry Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials	● pregnancy and in the fetus in humans?
		● in the healthy natural host	●  in gene therapy experiments	5.7 Does an animal model for antibody enhanced disease (including antibody dependent enhancement (ADE), vaccine associated enhanced respiratory disease (VAERD)) or immune complex disease exist?	● If no criteria were used for grading, or if other metrics were employed, please describe:	● elderly	●In any other special populations	9.8. Is the vaccine replication-competent in humans or other species?	10.8. What is known about biodistribution in animal models or in humans, including neurovirulence and/or neuroinvasion?	●If no criteria were used for grading, or if other metrics were employed, please describe:	● elderly
		● In laboratory hosts (specify species)	●  in any other special populations	5.8. What is known about biodistribution in animal models or in humans, including neurovirulence and/or neuroinvasion?	6.4. List and provide frequency of any related or possibly related serious* AE’s as well as any severe, expected or unexpected AE observed: (*see Instructions):	●  in any other special populations (e.g., institutionalized population, individuals with associated chronic comorbidity)?	8.3 Briefly, what are the key epidemiologic characteristics of the disease caused by the target pathogen (e.g. incubation period, communicable period, route/s of transmission, case fatality rate, transmissibility characteristics such as basic reproductive ratio (R0), and intrinsic mutation)?	9.9. What is the risk of reversion to virulence, recombination or reassortment with wild type virus or other agents?	10.9 What is the evidence that vector derived vaccines will generate a beneficial immune response in:	11.4. List and provide frequency of any related or possibly related serious* AE’s as well as any severe, expected or unexpected AE observed: (*see Instructions)	● in any other special populations (e.g., institutionalized population, individuals with associated chronic comorbidity)?
		●In healthy human host	4.4. Is the vector replication-competent in non-human species?	5.9 What is the evidence that vector derived vaccines will generate a beneficial immune response in:	6.5. List and provide frequency of any serious, unexpected significantly increased AE or lab abnormality in vaccinee vs. control group:	7.3. What is the potential for shedding and transmission in risk groups?	8.4 What sections of the population are most affected by the target pathogen (e.g. pediatric, pregnant, lactating women (breast feeding), adult, elderly)	9.10. Is the vaccine genetically stable in vitro and/or in vivo?	● Small animal models?	11.5. List and provide frequency of any serious, unexpected significantly increased AE or lab abnormality in vaccinee vs. control group:	12.3. What is the potential for shedding and transmission in risk groups?
		● In immunocompromised humans	4.5. What is the risk of reversion to virulence, recombination or reassortment with wild type virus or other agents?	●Small animal models?	●Describe the control group:	●Nonhuman primates (NHP)?	8.5 What is known about the immune responses, duration, and potential correlates of protective immunity to the target pathogen or to the disease?	9.11. What is the potential for shedding and transmission to humans or other species?	● Nonhuman primates (NHP)?	●      Describe the control group
		●      In breast milk, human neonates, infants, children	4.6 Is the vector genetically stable in vitro and/or in vivo?	● Nonhuman primates (NHP)?	6.6. List and provide frequency of Adverse Events of Special Interest		8.6 Please describe any other key information about the target pathogen or population that may inform benefit-risk	9.12. Does the vaccine establish a latent or persistent infection?	● Human?	11.6. List and provide frequency of Adverse Events of Special Interest
		●During pregnancy and in the unborn in humans	4.7. What is the potential for shedding and transmission, including arthropod borne transmission, to humans or other species?	●Human?	6.7. Did a Data Safety Monitoring Board (DSMB) or its equivalent oversee the study?			9.13. Does the vaccine replicate in the nucleus?	10.10. Have challenge or efficacy studies been conducted in subjects with:	11.7. Did a Data Safety Monitoring Board (DSMB) or its equivalent oversee the study?
		● In any other special populations?	4.8. Does the vector establish a latent or persistent infection?	5.10. Have challenge or efficacy studies been conducted in subjects with:	● Did it identify any safety issue of concern?			9.14. What is the risk of integration into the human genome?	● Immunocompromised conditions including HIV?	● Did it identify any safety issue of concern?
		3.8. What cell types are infected and what receptors are used in the natural host and in humans?	4.9. Does the vector replicate in the nucleus?	●  Immunocompromised conditions including HIV?	● If so describe:			9.15. List any disease manifestations caused by the vaccine in humans, the strength of evidence, severity, and duration of disease for the following categories:	●Other diseases?	● If so describe:
		3.9. What is known about the mechanisms of immunity to the wild type virus?	4.10. What is the risk of integration into the human genome?	●Other diseases?				● In healthy people	10.11 Have studies been done simultaneously or sequentially administering more than one vector with different transgenes? Is there evidence for interaction/interference?
		3.10 Has disease enhancement (including antibody dependent enhancement (ADE), vaccine associated enhanced respiratory disease (VAERD)) been demonstrated with the wild type virus:	4.11. Is there any previous human experience with this or a similar vector (safety and immunogenicity records)?	5.11 Have studies been done simultaneously or sequentially administering more than one vector with different transgenes? Is there evidence for interaction/interference?				●In immunocompromised people
		● in vitro?	4.12. What cell types are infected and what receptors are used in humans?					●In breast milk, neonates, infants, children
		● in animal models?	4.13. What is known about the mechanisms of immunity to the vector?					● During pregnancy and in the fetus
		● in human hosts?	4.14 Has disease enhancement (including antibody dependent enhancement (ADE), vaccine associated enhanced respiratory disease (VAERD)) been demonstrated with the vector?					●In any other special populations
		3.11 Is disease enhancement (including antibody dependent enhancement (ADE), vaccine associated enhanced respiratory disease (VAERD)) a possible vaccine-induced contributor to the pathogenesis of wild type disease	● in vitro?					9.16. What cell types are infected and what receptors are used in humans?
		3.12 What is the background prevalence of natural immunity to the virus?	● in animal models?					9.17. What is known about the mechanisms of immunity to the vaccine?
		3.13 Is there any vaccine available for the wild-type virus? If yes,	● in human hosts?					9.18 Has disease enhancement (including antibody dependent enhancement (ADE), vaccine associated enhanced respiratory disease (VAERD)) been demonstrated with the vaccine?
		● What populations are immunized?	4.15. Is there antiviral treatment available for disease manifestations caused by the vector?					● in vitro?
		● What is the background prevalence of artificial immunity?	4.16. Can the vector accommodate multigenic inserts or will several vectors be required for multigenic vaccines?					● in animal models?
		3.14 Is there treatment available for the disease caused by the wild type virus						● in human hosts?
								9.19 What is known about the effect of pre-existing immunity, including both natural immunity and repeat administration of the vector or the vaccine, on ‘take’, safety or efficacy in any animal model or human studies using this vector?
								9.20. Is the vaccine transmissible in humans or other species (including arthropods) and/or stable in the environment?
								9.21. Are there antiviral or other treatments available for disease manifestations caused by the vaccine?
								9.22. Vaccine formulation
								9.23. Proposed route and method of vaccine delivery (e.g. oral, intramuscular injection microneedles, skin patch, intranasal, mucosal)
								9.24. Target populations for the vaccine (e.g. pediatric, maternal, adult, elderly etc.)