National Center for Emerging and Zoonotic Infectious Diseases

Evidence for Expansion of Recommendations for PreExposure Vaccination with rVSVΔG-ZEBOV-GP Ebola 

Vaccine for Special Pathogens Treatment Centers and 

Laboratory Response Network Facilities

Advisory Committee on Immunization Practices

November 3, 2021

Jason Malenfant, MD, MPH

Epidemic Intelligence Service (EIS) Officer

Viral Special Pathogens Branch

Centers for Disease Control and Prevention
Policy Question 1

Should pre-exposure vaccination with the rVSVΔG-ZEBOV-GP 

vaccine be recommended for healthcare personnel* involved in 

the care and transport of suspect or confirmed Ebola virus 

disease patients at Special Pathogens Treatment Centers?
Policy Question 2

Should pre-exposure vaccination with the rVSVΔG-ZEBOV-GP 

vaccine be recommended for laboratorians and support staff at 

Laboratory Response Network (LRN) facilities that handle 

specimens that may contain replication-competent Ebola virus 

(species Zaire ebolavirus) in the United States?
Problem: Ebola Virus Disease Due to Ebola Virus 

(species Zaire ebolavirus)

Is the problem of public health importance?

No Probably no Uncertain Probably yes Yes Varies 
Problem: Ebola Virus Disease Due to Ebola Virus 

(species Zaire ebolavirus)

 Ebola virus (species Zaire ebolavirus) is the most lethal of the 4 viruses 

that cause Ebola virus disease (EVD) in humans

 Highly transmissible; found in all body fluids of an infected individual

 Severe disease, with death usually occurring 7-10 days after symptom 

onset

 In survivors, virus has been known to persist in immuno-privileged sites, 

and in some instances, has resulted in continued disease transmission and 

disease recrudescence
International Public Health Threat

 Ebola virus (species Zaire ebolavirus) is responsible for the majority of 

reported EVD outbreaks, including the largest EVD outbreak in history 

(2014 West Africa)

 Infected >31,000 persons and resulted in >12,000 deaths*

* Does not include ongoing 2018 DRC outbreak
U.S. Public Health Threat

 11 individuals infected with Ebola virus (species Zaire ebolavirus) have 

been treated in the United States

– All associated with 2014 West Africa Outbreak

– 9 were infected in West Africa

– 2 infected in the United States while caring for a returned traveler

 Additional persons were repatriated to the United States following highrisk exposures to confirmed EVD patients (2014 West Africa Outbreak, 

2018 DRC outbreak); none developed EVD
Problem: Ebola Virus Disease Due to Ebola Virus 

(species Zaire ebolavirus)

 Virus is responsible for the majority of reported EVD outbreaks

 >31,000 persons infected, resulting in >12,000 deaths

 International and U.S. public health threat

 High case fatality rate (70-90% when untreated)

Is the problem of public health importance?

No Probably no Uncertain Probably yes Yes Varies 
Problem: Ebola Virus Disease Due to Ebola Virus 

(species Zaire ebolavirus)

 Virus is responsible for the majority of reported EVD outbreaks

 >31,000 persons infected, resulting in >12,000 deaths

 International and U.S. public health threat

 High case fatality rate (70-90% when untreated)

Is the problem of public health importance?

No Probably no Uncertain Probably yes X Yes Varies 
Benefits

How substantial are the desirable anticipated effects?

Minimal Small Moderate Large Don’t know Varies 

 One study evaluated using GRADE provided data on vaccine efficacy

 Demonstrated protective effect from vaccination at the participant level

(RR: 0.04 [95%CI: 0.0001 – 0.74]) = 96% risk reduction
Benefits

How substantial are the desirable anticipated effects?

Minimal Small Moderate X Large Don’t know Varies 

 One study evaluated using GRADE provided data on vaccine efficacy

 Demonstrated protective effect from vaccination at the participant level

(RR: 0.04 [95%CI: 0.0001 – 0.74]) = 96% risk reduction
Harms

How substantial are the undesirable anticipated effects?

Minimal Small Moderate Large Don’t know Varies 

 Arthralgia is more commonly reported among vacinees (RR*: 2.55) 

 Severe arthralgia is more commonly reported among vaccine recipients; overall 

uncommon (RR*: 6.40)

 Arthritis is more commonly reported among vacinees (RR*: 1.80)

 Pregnancy loss in vaccinated women not significantly higher than in non-vaccinated 

women (RR*: 1.35 [95% CI: 0.73–2.52])

 rVSV vaccine virus detected post-vaccination in blood, saliva, urine, synovial fluid

 Vaccine-related serious adverse events (SAEs) are uncommon (3 events / 17,119 

vaccine recipients) *Reported RR for RCTs
Harms

How substantial are the undesirable anticipated effects?

Minimal Small X Moderate Large Don’t know Varies 

 Arthralgia is more commonly reported among vaccine recipients (RR*: 2.55)

 Severe arthralgia is more commonly reported among vaccine recipients; overall 

uncommon (RR*: 6.40)

 Arthritis is more commonly reported among vacinees (RR*: 1.80)

 Pregnancy loss in vaccinated women was not significantly higher than in nonvaccinated women (RR*: 1.35 [95% CI: 0.73–2.52])

 rVSV vaccine virus detected post-vaccination in blood, saliva, urine, synovial fluid

 Vaccine-related serious adverse events (SAEs) are uncommon (3 events / 17,119 

vaccine recipients) *Reported RR for RCTs
Benefit/Harms

Do the desirable effects outweigh the undesirable effects?

Favors intervention Favors comparison Favors both Favors neither Unclear

 Documented protective efficacy of the vaccine

 High severity of illness

 High transmissibility of Ebola virus

 Ebola virus persistence in survivors; instances of continued disease 

transmission and disease recrudescence

 Vaccine-related SAEs are uncommon
Benefit/Harms

Do the desirable effects outweigh the undesirable effects?

Favors intervention Favors comparison Favors both Favors neither Unclear

 Documented protective efficacy of the vaccine

 High severity of illness

 High transmissibility of Ebola virus

 Ebola virus persistence in survivors; instances of continued disease 

transmission and disease recrudescence

 Vaccine-related SAEs are uncommon

X
Overall Certainty for Evidence: Effectiveness

Effectiveness of the intervention

No included studies Very low Low Moderate High

 One study evaluated using the GRADE process demonstrated protective 

effect from vaccination 

 At the participant level, the overall certainty in the evidence for 

effectiveness is “Moderate” (level 2)

 At the cluster level, overall certainty in the evidence for effectiveness is 

“Low” (level 3)
Overall Certainty for Evidence: Effectiveness

Effectiveness of the intervention

No included studies Very low Low Moderate High

 One study evaluated using the GRADE process demonstrated protective 

effect from vaccination 

 At the participant level, the overall certainty in the evidence for 

effectiveness is “Moderate” (level 2)

 At the cluster level, overall certainty in the evidence for effectiveness is 

“Low” (level 3)

X
Overall Certainty for Evidence: Safety

Safety of the intervention

No included studies Very low Low Moderate High
Overall Certainty for Evidence: Safety

Safety of the intervention

No included studies Very low Low Moderate High

a. Outcome data was only collected from the vaccinated study arm from these studies; therefore they were considered observational for these outcomes

b. Overall evidence type for each outcome is determined by taking the lowest certainty value (highest evidence type) across both RCT and Obs for each outcome
Overall Certainty for Evidence: Safety

Safety of the intervention

No included studies Very low Low Moderate High

a. Outcome data was only collected from the vaccinated study arm from these studies; therefore they were considered observational for these outcomes

b. Overall evidence type for each outcome is determined by taking the lowest certainty value (highest evidence type) across both RCT and Obs for each outcome

X
Target Population Sentiments — HCP at Special 

Pathogens Treatment Centers

Does the target population feel that the desirable effects are large relative to 

undesirable effects?

No Probably no Uncertain Probably yes Yes Varies
Target Population Sentiments — HCP at Special 

Pathogens Treatment Centers

Does the target population feel that the desirable effects are large relative to 

undesirable effects?

No Probably no Uncertain Probably yes Yes Varies

 54% of the study population expressed interest in receiving the vaccine if 

eligible and offered the vaccine today

 When people were given the choice to get vaccinated at different time 

points (when there was an EVD case in the U.S. or their state), interest in 

vaccine increased to 81%

 53% of the survey population thought ACIP should vote to “recommend” 

the vaccine to HCP at Special Pathogens Treatment Centers
Target Population Sentiments — HCP at Special 

Pathogens Treatment Centers

Does the target population feel that the desirable effects are large relative to 

undesirable effects?

No Probably no Uncertain Probably yes Yes Varies

 54% of the study population expressed interest in receiving the vaccine if 

eligible and offered the vaccine today

 When people were given the choice to get vaccinated at different time 

points (when there was an EVD case in the U.S. or their state), interest in 

vaccine increased to 81%

 53% of the survey population thought ACIP should vote to “recommend” 

the vaccine to HCP at Special Pathogens Treatment Centers

X
Target Population Sentiments — HCP at Special 

Pathogens Treatment Centers

Is there important uncertainty about or variability in how much people value the main 

outcomes?

Important Possibly important Probably no No important No known

uncertainty uncertainty or important uncertainty or undesirable

or variability variability uncertainty or variability outcomes

variability 

 Mixed response to vaccination amongst HCP at Special Pathogens 

Treatment Centers, but interest in the vaccine increased markedly with 

perceived risk
Target Population Sentiments — HCP at Special 

Pathogens Treatment Centers

Is there important uncertainty about or variability in how much people value the main 

outcomes?

Important Possibly important Probably no No important No known

uncertainty uncertainty or important uncertainty or undesirable

or variability variability uncertainty or variability outcomes

variability 

 Mixed response to vaccination amongst HCP at Special Pathogens 

Treatment Centers, but interest in the vaccine increased markedly with 

perceived risk

X
Stakeholder Sentiments — HCP at Special Pathogens 

Centers

Is the intervention acceptable to key stakeholders?

No Probably no Uncertain Probably yes Yes Varies
Stakeholder Sentiments — HCP at Special Pathogens 

Centers

Is the intervention acceptable to key stakeholders?

No Probably no Uncertain Probably yes Yes Varies

 53% of the survey population thought ACIP should vote to “recommend” 

the vaccine to HCP at Special Pathogens Treatment Centers
Stakeholder Sentiments — HCP at Special Pathogens 

Centers

Is the intervention acceptable to key stakeholders?

No Probably no Uncertain Probably yes Yes Varies

 53% of the survey population thought ACIP should vote to “recommend” 

the vaccine to HCP at Special Pathogens Treatment Centers

X
Target Population Sentiments — Staff at LRN Facilities

Does the target population feel that the desirable effects are large relative to 

undesirable effects?

No Probably no Uncertain Probably yes Yes Varies
Target Population Sentiments — Staff at LRN Facilities

Does the target population feel that the desirable effects are large relative to 

undesirable effects?

No Probably no Uncertain Probably yes Yes Varies

 59% of the study population expressed interest in receiving the vaccine if 

eligible and offered the vaccine today

 When people were given the choice to get vaccinated at different time 

points (when there was an EVD case in the U.S. or their state), interest in 

vaccine increased to 86%

 59% of the survey population thought ACIP should vote to “recommend” 

the vaccine to staff at LRN facilities
Target Population Sentiments — Staff at LRN Facilities

Does the target population feel that the desirable effects are large relative to 

undesirable effects?

No Probably no Uncertain Probably yes Yes Varies

 59% of the study population expressed interest in receiving the vaccine if 

eligible and offered the vaccine today

 When people were given the choice to get vaccinated at different time 

points (when there was an EVD case in the U.S. or their state), interest in 

vaccine increased to 86%

 59% of the survey population thought ACIP should vote to “recommend” 

the vaccine to staff at LRN facilities

X
Target Population Sentiments — Staff at LRN Facilities

Is there important uncertainty about or variability in how much people value the main 

outcomes?

Important Possibly important Probably no No important No known

uncertainty uncertainty or important uncertainty or undesirable

or variability variability uncertainty or variability outcomes

variability 

 Mixed response to vaccination amongst staff at LRN facilities, but interest 

in the vaccine increased markedly with perceived risk
Target Population Sentiments — Staff at LRN Facilities

Is there important uncertainty about or variability in how much people value the main 

outcomes?

Important Possibly important Probably no No important No known

uncertainty uncertainty or important uncertainty or undesirable

or variability variability uncertainty or variability outcomes

variability 

 Mixed response to vaccination amongst staff at LRN facilities, but interest 

in the vaccine increased markedly with perceived risk

X
Stakeholder Sentiments — Staff at LRN Facilities

Is the intervention acceptable to key stakeholders?

No Probably no Uncertain Probably yes Yes Varies
Stakeholder Sentiments — Staff at LRN Facilities

Is the intervention acceptable to key stakeholders?

No Probably no Uncertain Probably yes Yes Varies

 59% of the survey population thought ACIP should vote to “recommend” 

the vaccine to staff at LRN facilities
Stakeholder Sentiments — Staff at LRN Facilities

Is the intervention acceptable to key stakeholders?

No Probably no Uncertain Probably yes Yes Varies

 59% of the survey population thought ACIP should vote to “recommend” 

the vaccine to staff at LRN facilities

X
Resource Allocation

Is the intervention a reasonable and efficient allocation of resources?

No Probably no Uncertain Probably yes Yes

 Cost effectiveness evaluation not performed as this vaccine is intended for 

use in preparedness scenarios in limited populations and not as routine 

vaccination in the general population

 At this time, the vaccine will be stored and made available through the 

U.S. government
Resource Allocation

Is the intervention a reasonable and efficient allocation of resources?

No Probably no Uncertain Probably yes Yes

 Cost effectiveness evaluation not performed as this vaccine is intended for 

use in preparedness scenarios in limited populations and not as routine 

vaccination in the general population

 At this time, the vaccine will be stored and made available through the 

U.S. government

X
Health Equity

What would be the impact on health equity? 

Reduced Probably reduced Probably no impact Probably increased Increased 

Varies Don’t know

 Only age, sex, and profession (job title) collected

 Race/ethnicity data from respondents not collected
Health Equity

What would be the impact on health equity?

Reduced Probably reduced Probably no impact Probably increased Increased 

Varies X Don’t know

 Only age, sex, and profession (job title) collected

 Race/ethnicity data from respondents not collected
Feasibility

Is the intervention feasible to implement?

No Probably no Uncertain Probably yes Yes Varies 

 Licensed doses are available through the Strategic National Stockpile
Feasibility

Is the intervention feasible to implement?

No Probably no Uncertain Probably yes Yes Varies 

 Licensed doses are available through the Strategic National Stockpile

X
Balance of Consequences for SPTCs and LRNs

Undesirable Undesirable Balance between 

consequences clearly consequences probably desirable and undesirable

outweigh desirable outweigh desirable consequences is closely 

consequences in most consequences in most balanced or uncertain

settings settings

Desirable consequences Desirable consequences There is insufficient evidence

probably outweigh clearly outweigh to determine the balance of

undesirable consequences undesirable consequences consequences

in most settings in most settings

X
Sufficiency of Information

Is there sufficient information to move forward with a recommendation?

Yes No

 Available efficacy data in an outbreak setting

 Safety data for 17,119 persons vaccinated in the U.S., Europe, Africa 

evaluated using GRADE

 Available data from vaccine acceptability surveys from both target 

populations
Sufficiency of Information

Is there sufficient information to move forward with a recommendation?

Yes No

 Available efficacy data in an outbreak setting

 Safety data for 17,119 persons vaccinated in the U.S., Europe, Africa 

evaluated using GRADE

 Available data from vaccine acceptability surveys from both target 

populations

X
Healthcare Personnel Definition

1 Healthcare personnel (HCP) refers to all paid and unpaid persons serving in healthcare 

settings who have the potential for direct or indirect exposure to patients or infectious 

materials, including body substances (e.g., blood, tissue, and specific body fluids); 

contaminated medical supplies, devices, and equipment; contaminated environmental 

surfaces; or contaminated air. These HCP include, but are not limited to, emergency 

medical service personnel, nurses, nursing assistants, physicians, technicians, clinical 

laboratory personnel, autopsy personnel, therapists, phlebotomists, pharmacists, 

students and trainees, contractual staff not employed by the healthcare facility, and 

persons not directly involved in patient care, but who could be exposed to infectious 

agents that can be transmitted in the healthcare setting (e.g., clerical, dietary, 

environmental services, laundry, security, engineering and facilities management, 

administrative, billing, and volunteer personnel). 

Adapted from https://www.cdc.gov/infectioncontrol/guidelines/healthcarepersonnel/index.html
References

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prevent Ebola in Liberia. New England Journal of Medicine; 2017. 

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Vaccine against Ebola. Emerg Infect Dis. 2020;26(3):541-548. 

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effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). The Lancet; 2017. 

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Included in meta-analyses (RCT or NRS with comparator); Not included in meta-analyses (NRS, without comparator)
For more information, contact CDC

1-800-CDC-INFO (232-4636)

TTY: 1-888-232-6348 www.cdc.gov

The findings and conclusions in this report are those of the authors and do not necessarily represent the 

official position of the Centers for Disease Control and Prevention.

National Center for Emerging and Zoonotic Infectious Diseases

Division of High-Consequence Pathogens and Pathology
Articles included in quantitative 

synthesis (meta-analysis)

(n = 9; studies= 8)

Evidence Retrieval

Additional records identified 

through other sources 

(n = 1)

Records excluded

(n = 1742)

Full-text articles excluded, with reasons

(n = 59)

41 Not relevant to outcomes 

8 Wrong study design 

7 Abstracts later published in full 

2 Wrong intervention 

1 Wrong population 

Records screened

(n = 1819)

Full-text articles 

assessed for eligibility

(n = 77)

Articles included in qualitative 

synthesis

(n = 18; studies = 11)

Records identified through 

database searching

(n = 1818)
Outcome 1: Development of Ebola-related symptomatic illness

Studies with unvaccinated comparator (n=1)

Henao-Restrepo, 2017: Ça Suffit Trial, Guinea

 Two-part Phase III cluster-randomized open-label, ring vaccination trial

– Initial study: contacts and contacts of contacts of confirmed EVD cases offered 

immediate vaccination vs delayed vaccination (21 days after randomization)

– Follow-up study: clusters were offered immediate vaccination following 

cessation of the randomized trial

 Primary outcome: incidence of EVD with onset 10 days or more from 

randomization

– Accounts for incubation period and unknown time for vaccinees to develop 

protective immunity
Immediately Vaccinated

N=Participants (clusters)

Delayed/Never vaccinated

N= Participants (clusters)

All participants, randomized and non-randomized 3775 (70) 4507 (104) a

Development of EVD ≥ 10 days after randomization, all participants b 0 (0) 23 (11)

Development of EVD < 10 days of randomization, all participants b 21 (11) 31 (22)

Randomized participants 2108 (51) 3075 (47) c

Development of EVD ≥ 10 days after randomization, randomized participants 0 (0) 16 (7)

Outcome 1: Development of Ebola-related symptomatic illness

Henao-Restrepo, 2017: Ça Suffit Trial, Guinea (Final Results)

a. Refers to all eligible in delayed plus all eligible never-vaccinated in immediate group 

b. For non-randomized participants the date of inclusion in the ring was used

c. Refers to all eligible participants (clusters) randomized to delayed/never vaccinated group 

d. Efficacy calculation based on randomized participants who developed EVD ≥ 10 day after randomization 

Vaccine efficacy 100% (95% CI: 68.9 – 100, p=0.0045) d
Immediately Vaccinated

N=Participants (clusters)

Delayed/Never vaccinated

N= Participants (clusters)

All participants, randomized and non-randomized 3775 (70) 4507 (104) a

Development of EVD ≥ 10 days after randomization, all participants b 0 (0) 23 (11)

Development of EVD < 10 days of randomization, all participants b 21 (11) 31 (22)

Randomized participants 2108 (51) 3075 (47) c

Development of EVD ≥ 10 days after randomization, randomized participants 0 (0) 16 (7)

a. Refers to all eligible in delayed plus all eligible never-vaccinated in immediate group 

b. For non-randomized participants the date of inclusion in the ring was used

c. Refers to all eligible participants (clusters) randomized to delayed/never vaccinated group 

d. Efficacy calculation based on randomized participants who developed EVD ≥ 10 day after randomization 

Outcome 1: Development of Ebola-related symptomatic illness

Henao-Restrepo, 2017: Ça Suffit Trial, Guinea (Final Results)

Vaccine efficacy 100% (95% CI: 68.9 – 100, p=0.0045) d
GRADE Evidence Assessment Criteria

 Initial evidence type (certainty level) determined by study design

- Initial evidence type 1 (high certainty): A body of evidence from randomized controlled 

trials

- Initial evidence type 3 (low certainty): A body of evidence from observational studies

 Risk of bias: Can include failure to conceal allocation, failure to blind, loss to follow-up. Risk 

of bias may vary across outcomes.

 Inconsistency: Criteria for evaluating include similarity of point estimates, extent of overlap 

of confidence intervals, and statistical criteria including tests of heterogeneity and I2

 Indirectness: Considers the generalizability of the evidence to the original PICO components 

(i.e. pre-exposure immunization in the U.S. population)

 Imprecision: Considers the fragility of the relative and absolute effect measures based on the 

interpretation of the 95% CIs and the optimal information size

 Other considerations: Includes publication bias or indications of dose-response gradient, 

large or very large magnitude of effect, and opposing residual confounding
Overall Evidence Types (Certainty Levels)

 Type 1 (high certainty): We are very confident that the true effect lies 

close to that of the estimate of the effect.

 Type 2 (moderate certainty): We are moderately confident in the effect 

estimate: The true effect is likely to be close to the estimate of the effect, 

but there is a possibility that it is substantially different.

 Type 3 (low certainty): Our confidence in the effect estimate is limited: 

The true effect may be substantially different from the estimate of the 

effect.

 Type 4 (very low certainty): We have very little confidence in the effect 

estimate: The true effect is likely to be substantially different from the 

estimate of the effect
Evidence Table: Development of Ebola-related symptomatic illness

Summary: rVSVΔG-ZEBOV-GP is effective at preventing Ebola virus disease

Certainty assessment No of patients Effect

Certainty Importance

No of 

studies Study design Risk of bias Inconsistency Indirectness Imprecision Other 

considerations

rVSVvaccineno rVSVvaccineRelative

(95% CI)

Absolute

(95% CI)

1 9 Randomized a

(clusters)

not 

serious 

not 

serious serious b serious c none 

0/51 

(0.0%)

7/47 

(14.9%)

RR 0.06 g

(0.0001 to 

1.05) 

140 fewer per 

1,000

(from 149 

fewer to 7 

more) 

LOW

Evidence 

type 3 

CRITICAL 

1 9 Observational d

(participants)

not 

serious 

not 

serious serious b not serious 

strong 

association e

0/2108 f

(0.0%) 

16/307

5 

(0.5%)

RR 0.04 g

(0.0001 to 

0.74) 

5 fewer per 

1,000

(from 5 fewer 

to 1 fewer

MODERATE e

Evidence 

type 2

CRITICAL

Explanations

a. Henao-Restrepo 2017 was a cluster randomized trial where units of randomization were clusters; cluster-level data presented here

b. Concern for indirectness to US population: population consists of contacts and contacts of contacts of EVD case, ring vaccination strategy which may include postexposure vaccination

c. Because this study was done at a time when the 2014-2015 West Africa outbreak was waning in Guinea and there are few events reported it does not meet optimal 

information size and suggests fragility in the estimate; 95% C.I. contains the potential for desirable as well as undesirable effects

d. Henao-Restrepo 2017 was a cluster randomized trial (i.e. units of randomization were clusters); participant-level data presented here

e. The concerns with indirectness pose no inflationary effect; therefore, the evidence was rated up based on a very large magnitude of effect from the 96% RR reduction 

and overall certainty was upgraded two levels

f. Denominator represents participants from the clusters randomized to received immediate vaccination

g. RR calculated using the standard continuity correction of 0.5 CI: Confidence interval; RR: Relative risk

Note: Outcome assessed with laboratory confirmed case of EVD
Note: Observational studies with no comparator groups are not included in evidence table, but would be considered of very low certainty (evidence type 4)

Objective 2: Incidence of Arthralgia (0-42 days)

Summary: Arthralgia is more commonly reported among vaccine recipients compared to unvaccinated

Certainty assessment No of patients Effect

Certainty Importance No of 

studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations

rVSV-ZEBOV 

vaccine

no rVSV-ZEBOV 

vaccine

Relative

(95% CI)

Absolute

(95% CI)

6 

1,2,4,5,6,

7

Randomized 

trials serious a serious b not 

serious serious c none 

316/1874 

(16.9%) 

42/891 

(4.7%) 

RR 2.55e

(0.94 to 

6.91) 

73 more per 

1,000

(from 3 fewer 

to 279 more) 

VERY LOW 

Evidence 

type 4

CRITICAL 

2 3,6 Observational 

studies

not 

serious 

not 

serious 

not 

serious serious d none 

75/469 

(16.0%) 

8/99 

(8.1%) 

RR 1.63e

(0.0001 to 

986.24) 

51 more per 

1,000

(from 81 

fewer to 

1,000 more) 

VERY LOW 

Evidence 

type 4

CRITICAL 

Explanations

a. Participants, healthcare personnel, and outcome assessors were not blinded in Huttner 2015 or Samai 2018 potentially influencing events reported for this 

subjective outcome. Concern for possible underreporting in Kennedy because arthralgia was only solicited at one week and at one month for the majority of 

participants; Huttner only solicited arthralgia for low dose participants

b. Concerns with heterogeneity (I2=70%) some may be explained by concerns with risk of bias (poor randomization or outcome definition)

c. The 95% confidence interval includes potential for possible harms as well as benefits 

d. Few events reported do not meet optimal information size and suggest fragility in the estimate. 

e. RR calculated using the standard continuity correction of 0.5 CI: Confidence interval; RR: Relative risk
Outcome 3: Severity of arthralgia (0-42 days)

Summary: Severe (grade 3) arthralgia is more commonly reported among vaccine recipients compared to 

unvaccinated, but is overall uncommon

Certainty assessment No of patients Effect

No of Certainty Importance

studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations

rVSV-ZEBOV 

vaccine

no rVSVZEBOV vaccineRelative

(95% CI)

Absolute

(95% CI)

4 1,5,6,7 Randomized 

trials serious a not serious not serious serious b none 

2/333 

(0.6%) 

0/264 

(0.0%) 

RR 6.40 c

(0.0001 to 

27950.69) 

0 fewer per 

1,000

(from 0 fewer 

to 0 fewer) 

LOW 

Evidence 

type 3

CRITICAL 

2 3,6 Observationa

l studies 

not 

serious not serious not serious serious b none 

No events of grade 3 arthralgia were reported 

among 469 vaccinated and 99 non-vaccinated 

participants d

VERY LOW

Evidence 

type 4

CRITICAL 

Explanations

a. Participants, healthcare personnel, and outcome assessors were not blinded in Huttner 2015 or Samai 2018 potentially influencing events reported for this 

subjective outcome. Huttner only solicited arthralgia for low dose participants. 

b. Few events reported do not meet optimal information size and suggest fragility in the estimate. 

c. Risk ratios (RR) were calculated using a 0.1 continuity correction due to low numbers of reported events.

d. Huttner 2015 did not solicit arthralgia for high-dose participants; these data were excluded from analysis.

Note: Observational studies with no comparator groups are not included in evidence table, but would be considered of very low certainty (evidence type 4)

CI: Confidence interval; RR: Relative risk
Note: Observational studies with no comparator groups are not included in evidence table, but would be considered of very low certainty (evidence type 4)

Outcome 4: Incidence of arthritis (5-56 days)

Summary: Arthritis is more commonly reported among vaccine recipients compared 

to unvaccinated

Certainty assessment No of patients Effect

Certainty Importance No of 

studies Study design Risk of bias Inconsistency Indirectness Imprecision

Other 

consideration

s

rVSV-ZEBOV 

vaccine

no rVSVZEBOV 

vaccine

Relative

(95% CI)

Absolute

(95% CI)

4 1,2,4,5 Randomized 

trials 

serious a not serious not 

serious 

serious b none 39/1776 

(2.2%) 

16/868 

(1.8%) 

RR 1.80d

(0.21 to 

15.13) 

23 more per 

1,000

(from 22 fewer 

to 400 more) 

LOW 

Evidence 

type 3

CRITICAL 

2 3,6 Observationa

l studies 

not 

serious 

not serious not 

serious 

very 

serious 

b,c

none 43/520 

(8.3%) 

3/107 

(2.8%) 

RR 2.06d

(0.0001 to 

7739.16) 

33 more per 

1,000

(from 28 fewer 

to 1,000 more) 

VERY LOW

Evidence 

type 4 

CRITICAL 

Explanations

a. Studies used variable definitions and methods for diagnosing and reporting arthritis. In addition, participants, healthcare personnel, and outcome assessors 

were not blinded in Huttner 2015 or Samai 2018 potentially influencing events reported for this subjective outcome. 

b. The 95% CI includes the potential for possible harms, as well as possible benefit. 

c. Few events reported do not meet optimal information size and suggest fragility in the estimate. 

d. Risk ratios (RR) calculated using the standard continuity correction of 0.5 CI: Confidence interval; RR: Relative risk
Outcome 5: Vaccine-related pregnancy adverse events 

Summary: The rate of pregnancy loss among pregnant women who received immediate vaccination was not 

significantly higher than the rate of pregnancy loss among unvaccinated pregnant women

Certainty assessment No of patients Effect

Certainty Importance No of 

studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations

rVSV-ZEBOV 

vaccine

no rVSV-ZEBOV 

vaccine

Relative

(95% CI)

Absolute

(95% CI)

18 Observationa

l

not 

serious a

not serious serious b very 

serious c,d

none 14/31 

(45.2%) 

11/33 

(33.3%) 

RR 1.35

(0.73 to 

2.52) 

117 more per 

1,000

(from 90 fewer 

to 507 more) 

VERY LOW 

Evidence 

type 4

CRITICAL 

Explanations

a. Participants, study personnel, and outcome assessors were unblinded and could have potentially influenced risk behaviors, though likely did not have an 

impact on risk of bias

b. Legardy-Williams et al. report on the outcome of pregnancy loss as a measure of vaccine-related pregnancy adverse events; however, the study did not 

differentiate between spontaneous abortions (which includes induced abortion) and stillbirths. The outcome may not accurately distinguish between those 

events due to the vaccine. In addition, we are not certain about the events reported that are directly related to receipt of the vaccine. 

c. The 95% CI includes the potential for possible harms, as well as possible benefit. 

d. Few events reported do not meet optimal information size and suggest fragility in the estimate. 

Note: Observational studies with no comparator groups are not included in evidence table, but would be considered of very low certainty (evidence type 4)

CI: Confidence interval; RR: Relative risk
Evidence Table: Detection of rVSV in blood/plasma by RT-PCR

Summary: rVSVΔG-ZEBOV-GP has been detected by RT-PCR in blood/plasma up to 14 days postvaccination; however, true duration of shedding and potential for transmissibility is uncertain

Certainty assessment

No of Summary of Findings Certainty Importance

studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations

8

2,3,5,6,7,10, 

11,13

Observationa

l studiesa

serious b not serious very 

serious c

not serious none Longest recorded positive RT-PCR in blood 

or plasma is 14 days post-vaccination; 

26/691 (3.7%) positive at day 7; 1/501 

(0.2%) vaccinees positive at day 14. 

VERY 

LOW 

(Evidence 

type 4)

CRITICAL 

Explanations

a. Outcome data was only collected from the vaccinated study arm from these studies; therefore they were considered observational for these outcomes

b. Not all who received the vaccine were tested; concern for incomplete outcome data. Heppner 2017: 46/60 were tested on day 3, 49/60 were tested on day 

7, and 30/60 were tested on day 14. 

c. The outcome of interest is transmissibility of the vaccine virus to humans or animals. No data is available for, so viral dissemination and shedding is assessed 

as an indirect surrogate. RT-PCR positivity is not synonymous with infectivity. 
Evidence Table: RT-PCR detection of rVSV in saliva and urine

Summary: VSVΔG-ZEBOV-GP has been detected in saliva up to 14 days and urine up to 7 days postvaccination; however, true duration of shedding and potential for transmissibility is uncertain

Certainty assessment

No of Summary of Findings Certainty Importance

studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations

43,5,7,11 Observational 

studies a

serious b not serious very 

serious c

not 

serious 

none Longest recorded positive RT-PCR in 

saliva is 14 days post-vaccination; 6/257 

(2.3%) positive at day 7; 1/98 (1.0%) 

vaccinees positive at day 14.

Longest recorded positive RT-PCR in 

urine is 7 days post-vaccination; 2/246 

(0.8%) positive at day 7; 0/98 positive at 

day 14. 

VERY LOW 

(Evidence 

type 4)

CRITICAL 

Explanations

a. Outcome data was only collected from the vaccinated study arm from these studies; therefore they were considered observational for these outcomes

b. Not all who received the vaccine were tested; concern for incomplete outcome data. ElSherif: Virus in urine and saliva were only tested if viremia was 

detected at or above the level of quantification; Heppner 2017: 46/60 were tested on day 3, 49/60 were tested on day 7, and 30/60 were tested on day 

14. 

c. The outcome of interest is transmissibility of the vaccine virus to humans or animals. No data is available for, so viral dissemination and shedding is 

assessed as an indirect surrogate. RT-PCR positivity is not synonymous with infectivity. 
Evidence Table: Vaccine-related serious adverse 

events

Summary: Vaccine-related SAEs are an uncommon occurrence

Certainty assessment

No of Summary of Findings Certainty Importance

studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations

12

1,3,4,5,6

,7,10,11,

12,13,14

,15

Observationa

l studies a

not 

serious

not serious not 

serious

not 

serious 

none Across 12 studies, 3/17,119 

(0.02%) vaccinees were judged to 

have an SAE related to or possibly 

related to vaccination. 

LOW 

(Evidence type 3)

CRITICAL 

Explanations

a. Outcome data was only collected from the vaccinated study arm from these studies; therefore they were considered observational for these outcomes

b. Overall evidence type is 3 (low certainty) because these 12 studies were considered observational for these outcomes as data was only collected from the 

vaccinated study arm from these studies without a comparator; however there was no downgrading of the evidence.
Evidence Table: Development of Ebola-related symptomatic illness

Summary: rVSVΔG-ZEBOV-GP is effective at preventing Ebola virus disease

Certainty assessment No of patients Effect

Certainty Importance

No of 

studies Study design Risk of bias Inconsistency Indirectness Imprecision Other 

considerations

rVSVvaccineno rVSVvaccineRelative

(95% CI)

Absolute

(95% CI)

1 9 Randomized a

(clusters)

not 

serious 

not 

serious serious b serious c none 

0/51 

(0.0%)

7/47 

(14.9%)

RR 0.06 g

(0.0001 to 

1.05) 

140 fewer per 

1,000

(from 149 

fewer to 7 

more) 

LOW

Evidence 

type 3 

CRITICAL 

1 9 Observational d

(participants)

not 

serious 

not 

serious serious b not serious 

strong 

association e

0/2108 f

(0.0%) 

16/307

5 

(0.5%)

RR 0.04 g

(0.0001 to 

0.74) 

5 fewer per 

1,000

(from 5 fewer 

to 1 fewer

MODERATE e

Evidence 

type 2

CRITICAL

Explanations

a. Henao-Restrepo 2017 was a cluster randomized trial where units of randomization were clusters; cluster-level data presented here

b. Concern for indirectness to US population: population consists of contacts and contacts of contacts of EVD case, ring vaccination strategy which may include postexposure vaccination

c. Because this study was done at a time when the 2014-2015 West Africa outbreak was waning in Guinea and there are few events reported it does not meet optimal 

information size and suggests fragility in the estimate; 95% C.I. contains the potential for desirable as well as undesirable effects

d. Henao-Restrepo 2017 was a cluster randomized trial (i.e. units of randomization were clusters); participant-level data presented here

e. The concerns with indirectness pose no inflationary effect; therefore, the evidence was rated up based on a very large magnitude of effect from the 96% RR reduction 

and overall certainty was upgraded two levels

f. Denominator represents participants from the clusters randomized to received immediate vaccination

g. RR calculated using the standard continuity correction of 0.5 CI: Confidence interval; RR: Relative risk

Note: Outcome assessed with laboratory confirmed case of EVD
GRADE Evidence Assessment Criteria

 Initial evidence type (certainty level) determined by study design

- Initial evidence type 1 (high certainty): A body of evidence from randomized controlled 

trials

- Initial evidence type 3 (low certainty): A body of evidence from observational studies

 Risk of bias: Can include failure to conceal allocation, failure to blind, loss to follow-up. Risk 

of bias may vary across outcomes.

 Inconsistency: Criteria for evaluating include similarity of point estimates, extent of overlap 

of confidence intervals, and statistical criteria including tests of heterogeneity and I2

 Indirectness: Considers the generalizability of the evidence to the original PICO components 

(i.e. pre-exposure immunization in the U.S. population)

 Imprecision: Considers the fragility of the relative and absolute effect measures based on the 

interpretation of the 95% CIs and the optimal information size

 Other considerations: Includes publication bias or indications of dose-response gradient, 

large or very large magnitude of effect, and opposing residual confounding
Overall Evidence Types (Certainty Levels)

 Type 1 (high certainty): We are very confident that the true effect lies 

close to that of the estimate of the effect.

 Type 2 (moderate certainty): We are moderately confident in the effect 

estimate: The true effect is likely to be close to the estimate of the effect, 

but there is a possibility that it is substantially different.

 Type 3 (low certainty): Our confidence in the effect estimate is limited: 

The true effect may be substantially different from the estimate of the 

effect.

 Type 4 (very low certainty): We have very little confidence in the effect 

estimate: The true effect is likely to be substantially different from the 

estimate of the effect