National Center for Emerging and Zoonotic Infectious Diseases

Review of GRADE & Overview of State Designated 

ETCs and Laboratory Response Network

Amy Whitesell, MPH

Viral Special Pathogens Branch

Centers For Disease Control and Prevention

Advisory Committee on Immunization Practices

November 3, 2021
Overview

 Review outcomes evaluated by GRADE (presented during February 2020 

meeting)

 State designated Ebola treatment centers

– Define population

– Review vaccine acceptability survey results

 Laboratory Response Network facilities

– Define population

– Review vaccine acceptability survey results
Review of GRADE: rVSVΔG-ZEBOV-GP 

Ebola vaccine (February 2020)
Population

Healthy, non-pregnant, non-lactating adults 18 years of age or older in the U.S. population who are at risk of 

occupational exposure to Ebola virus (species Zaire ebolavirus); Subgroups: 1) Individuals responding to an 

outbreak of Ebola virus disease due to Ebola virus (species Zaire ebolavirus); 2) healthcare personnel involved in 

the care and transport of confirmed EVD patients at federally-designated Ebola Treatment Centers in the United 

States; 3) laboratorians and support staff working at biosafety level 4 (BSL-4) laboratories that handle a) cultures 

or b) animals infected with replication-competent Ebola virus or c) diagnostic or clinical specimens containing 

replication-competent Ebola virus

Intervention Pre-exposure intramuscular immunization with a single licensed dose of the rVSVΔG-ZEBOV-GP vaccine

Comparison No vaccine

Outcomes 

deemed “Critical” 

or “Important” by 

ACIP Ebola vaccine 

Work Group

 Development of Ebola-related symptomatic illness (Critical)

 Vaccine-related joint pain or swelling (arthritis or arthralgia) (Critical)

 Vaccine-related adverse pregnancy outcomes for women inadvertently vaccinated while pregnant and 

women who become pregnant within in 2 months of vaccination (Critical)

 Transmissibility of rVSV vaccine virus: Surrogate assessed with viral dissemination/shedding of the rVSV 

vaccine virus (Critical)

 Serious adverse events related to the vaccination (Critical)
Critical Outcomes Evaluated by GRADE

 Benefits (Efficacy)

1. Development of Ebola-related symptomatic illness

 Safety

1. Incidence of arthralgia

2. Severity of arthralgia: events of grade 3 (severe) arthralgia 

3. Incidence of arthritis

4. Vaccine-related adverse pregnancy outcomes for women inadvertently 

vaccinated while pregnant and women who become pregnant within in 2 

months of vaccination

5. Detection of rVSV vaccine virus in blood or plasma (viremia), saliva (viral 

shedding), and urine (viral shedding)

6. Serious adverse events related to vaccination 
Benefits: Development of Ebola-related symptomatic 

illness

1 study with unvaccinated comparator [Henao-Restrepo, 2017]

 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

– Vaccine efficacy at the cluster level: 100% [95% CI: 68.9 – 100, p=0.0045]

– RR at the participant level: 0.04 [95% CI: 0.0001 – 0.74] 

– AR at the participant level: 5 fewer per 1,000 (from 5 fewer to 1 fewer)
Safety: Incidence of Arthralgia (0-42 days) 

8 studies with unvaccinated comparator solicited arthralgia within 0-42 days

 Included 6 randomized control trials: 

– Arthralgia reported in 316/1874 (16.9%) vaccinated participants compared to 

42/891 (4.7%) nonvaccinated participants 

– RR: 2.55 [95% CI: 0.94-6.91]

– AR: 73 more per 1,000 (from 3 fewer to 279 more) 
Safety: Severity of Arthralgia (0-42 days) 

6 studies with unvaccinated comparator reported arthralgia severity within 

0-42 days

 Included 4 randomized control trials: 

– Grade 3 arthralgia reported in 2/333 (0.6%) vaccinated participants compared 

to 0/264 (0.0%) nonvaccinated participants

– RR: 6.40 [95% CI: 0.0001-27950.69]

– AR: 0 fewer per 1,000 (from 0 fewer to 0 fewer) 
Safety: Incidence of Arthritis (5-56 days)

6 studies with unvaccinated comparator 

 Included 4 randomized control trials

– Arthritis reported in 39/1776 (2.2%) vaccinated participants compared to 

16/868 (1.8%) nonvaccinated participants

– RR: 1.80 [95% CI: 0.21-15.13] 

– AR: 23 more per 1,000 (from 22 fewer to 400 more) 

3 studies performed synovial fluid testing

 Vaccine virus has been detected by RT-PCR in four out of seven vaccinated 

participants that have had synovial fluid tested
1 study with unvaccinated comparator [Legardy-Williams, 2020]

 Primary outcome: incidence of pregnancy loss in women inadvertently 

vaccinated while pregnant and women who became pregnant within 2 

months of vaccination

– Pregnancy loss experienced by 14/31 (45%) immediately vaccinated pregnant 

women compared to 11/33 (33%) unvaccinated pregnant women 

– RR: 1.35 [95% CI 0.73-2.52] 

– AR: 117 more per 1,000 (from 90 fewer to 507 more)

– Overall, 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

Safety: Vaccine-related adverse pregnancy outcomes
Safety: Detection of rVSV vaccine virus in blood or 

plasma, saliva, and urine

Abbreviation: dpv = days postvaccination; rRT-PCR = reverse transcriptase-polymerase chain reaction.

*One study also tested at 28 dpv and 0/38 samples were positive [Heppner, 2017]

†One study performed viral isolation on selected blood specimens, all negative [Agnandji, 2016]

‡Not included in GRADE assessment, data from Ervebo Package Insert

§Of three participants with rash in one study, all were positive by rRT-PCR up to 17 dpv. Virus isolation was positive in one specimen with the 

highest RNA level 9 dpv [Agnandji, 2016]

Note: true estimate of duration of shedding is unknown because daily collection not performed

Specimen 

type

Number 

of studies 

included 

in GRADE

Vaccine 

virus 

detected 

by rRT-PCR

Longest 

recorded 

positive rRTPCR (dpv)

Culture of 

vaccine virus 

attempted

Vaccine virus 

detected by 

culture

Blood 8 Yes 14* Yes† No

Saliva 4 Yes 14* No Not performed

Urine 4 Yes 7* No Not performed

Skin vesicles‡ NA Yes 20 Yes Yes

§
Safety: Vaccine-related serious adverse events

12 clinical trials and two additional publications reported on vaccine-related 

serious adverse events (SAEs)

 3/17,119 (0.02%) vaccinees judged to have a SAE related or possibly 

related to the vaccine were reported

– 2 SAEs related to vaccination: a febrile reaction and anaphylaxis, both which 

resolved without sequelae [Henao-Restrepo, 2017]

– 1 SAE possibly related to the vaccine: influenza like illness, which resolved 

without sequelae [Henao-Restrepo, 2017]

 An additional case of anaphylaxis was identified in data provided to the 

FDA and resolved without sequelae
GRADE Summary

Comparison: One dose rVSVΔG-ZEBOV-GP versus placebo or no vaccine in adults ≥18

Outcome Design 

(# of studies) Findings Evidence type†

Benefits

Prevent Ebola virus disease RCT (1) rVSVΔG-ZEBOV-GP is effective at preventing Ebola virus disease 3

Safety

Incidence of arthralgia RCT (6)

Obs (1)

Arthralgia is more commonly reported among vaccine recipients 

compared to placebo 4

Severity of arthralgia RCT (4)

Obs (1)

Severe (grade 3) arthralgia is more commonly reported among vaccine 

recipients compared to placebo or unvaccinated, but is overall uncommon 4

Incidence of arthritis RCT (5)

Obs (1)

Arthritis is more commonly reported among vaccine recipients compared 

to placebo 4

Pregnancy-related adverse 

events due to vaccination Obs (1)

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

4

Transmissibility of vaccine-virus

Blood/plasma

Saliva

Urine

Obs* (7)

Obs* (4)

Obs* (4)

rVSVΔG-ZEBOV-GP has been detected in blood/plasma up to 14 days, 

saliva 7 days, and urine 7 days post-vaccination; however, true duration of 

shedding and potential for transmissibility is uncertain

4

Vaccine-related serious adverse 

events

Obs* (12) Vaccine-related SAEs are an uncommon occurrence (3 events in 17,119 

vaccine recipients across 12 studies) 3

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

†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
Populations of Interest
Recap of Ebola Virus Vaccine Session, February 2021

 Identified 2 additional U.S. populations at risk for potential occupational 

exposure to Ebola virus (species Zaire ebolavirus)

– Healthcare personnel* (HCP) at state designated Ebola Treatment Centers 

involved in the care and transport of suspect or confirmed EVD patients

–

*See slide #31
State Designated ETCs

 Designated by states

 Council of State and Territorial Epidemiologists (CSTE) WG has determined 

the preferred terminology for these facilities: Special Pathogens 

Treatment Centers (SPTC)

 SPTCs have been defined as*:

– Healthcare facilities that intend to receive and are able to provide care for a 

suspect or confirmed patient with Ebola virus disease (EVD) for the duration of 

their illness, as assessed by their state health department. In addition to EVD, 

these facilities may also be designated by the states to treat other high 

consequence pathogens.

 Currently 55 SPTC facilities identified

*Definition adapted from: https://www.cdc.gov/vhf/ebola/healthcare-us/preparing/treatment-centers.html
Vaccine Acceptability Survey: Special Pathogen 

Treatment Centers

Survey responses received

(n = 364)

Responses included in data analysis

(n = 298)

Survey responses excluded due to incompleteness 

(n = 66)

Facilities identified

(n = 51)

Sent survey invitation

(n = 49)

Facilities missing point of contact information

(n = 2)
Demographics: Profession (n = 298)

Profession n %

Nurse 116 39%

Doctor 67 22%

Respiratory Therapist 25 8%

EMT 22 7%

Advanced Practice Provider 22 7%

Laboratory Technician 20 7%

Manager/Safety Officer 14 5%

Other 9 3%

Environmental Services 3 1%
If you were eligible for vaccination and offered the 

rVSV Ebola vaccine today*, would you choose to be 

vaccinated? (n=298)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1 2

*Today refers to the time between October 14th – January 22nd 2021 when the individual took the survey. During this time, the Ebola outbreak in 

Equateur Province, DRC was declared over on November 18th, 2020.

n = 160 n = 138

54%

46%
When would you choose to get vaccinated: 

(n=298)

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%

1 2 3 4

23%

25%

33%

19%

n = 97 n = 57

When we gave 

participants an 

option of 

choosing when 

to get 

vaccinated, the 

interest in 

vaccine rose to 

81%.

n = 70 n = 74
Do you think ACIP should vote to “recommend” the 

rVSV vaccine to healthcare personnel at your facility1? 

(n=298)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1 2 3

53%

9%

38%

n = 158 n = 27 n = 113

*Did not ask about “Shared Clinical Decision Making”.
Conclusions

 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%

 Concern for a serious adverse event and transmission of the vaccine virus

to others were top concerns for study participants

*Today refers to the time between October 14th – January 22nd 2021 when the individual took the survey. During this time, the Ebola outbreak in 

Equateur Province, DRC was declared over on November 18th, 2020.
Recap of Ebola Virus Vaccine Session, February 2021

 Identified 2 additional U.S. populations at risk for potential occupational 

exposure to Ebola virus (species Zaire ebolavirus)

–

– Individuals who work as laboratorians and support staff at Laboratory 

Response Network (LRN) facilities that handle replication competent Ebola 

virus (species Zaire ebolavirus)
Defining Laboratory Response Network Facilities

 The Laboratory Response Network 

(LRN) quickly responds to biological 

and chemical threats and other 

public health emergencies

 Ebola testing is available at ~58 

LRN labs in the US

 Estimate 10-15 laboratorians who 

can do Ebola testing per facility

Image received from https://www.cdc.gov/anthrax/lab-testing/isitanthrax.html
Vaccine Acceptability Survey: Laboratory Response 

Network Facilities

Survey responses received

(n = 96)

Responses included in data analysis

(n = 70)

Survey responses excluded due to incompleteness 

(n = 26)

LRN facilities identified

(n = ~1,133)

Sent survey invitation

(n = 62)

Facilities without Ebola testing capacity

(n = 1,071)
Demographics: Profession (n = 70)

Profession n %

Laboratory Scientist 45 64%

Management 21 30%

Other 4 6%

 Survey respondents were given the options of: laboratory scientist, 

clerk or receptionist, environmental services, manager, or other.

 Of the four individuals who self-identified as other, all four described 

themselves as Director or Laboratory Director.
If you were eligible for vaccination and offered the 

rVSV Ebola vaccine today*, would you choose to be 

vaccinated? (n=70)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1 2

*Today refers to the time between December 29th – January 21st 2021 when the individual took the survey. During this time, there were no active 

Ebola virus outbreaks in the world.

59%

41%

n = 41 n = 29
When would you choose to get vaccinated 

(n=70):

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%

1 2 3 4

34%

29%

23%

14%

n = 24 n = 20 n = 16 n = 10

When we gave 

participants an 

option of 

choosing when to 

get vaccinated, 

the interest in 

vaccine rose to 

86%.
Do you think ACIP should vote to “recommend” the 

rVSV vaccine to staff at LRN facilities*? (n=70)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1 2 3

59%

9%

33%

n = 41 n = 6 n = 23

*Did not ask about “Shared Clinical Decision Making”.
Conclusions

 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 US or their state), interest in 

vaccine increased to 86%

 Common reasons for not wanting the vaccine were low risk of exposure

and concerns about potential side effects (especially arthritis)

*Today refers to the time between December 29th – January 21st 2021 when the individual took the survey. During this time, there were no 

active Ebola virus outbreaks in the world.
Healthcare Personnel Definition

* 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
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
Additional Slides
Policy Question

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

recommended for healthy, non-pregnant, non-lactating adults 18 years of 

age or older in the U.S. population who are at potential occupational risk to 

exposure to Ebola virus (species Zaire ebolavirus) for prevention of Ebola 

virus infection?
Evidence Retrieval

 Literature search of multiple biomedical and interdisciplinary bibliographic 

databases including: Medline, Embase, Global Health, CINAHL, Cochrane Library, 

Scopus and Clinicaltrials.gov

 A broad and rigorous strategy incorporating terms related to the concept of 

vaccination against Ebola virus using the rVSVΔG-ZEBOV-GP vaccine, without date 

or language restrictions, was used to identify potentially relevant studies

 Results were compiled in an Endnote Library and duplicate records were removed 

 The search was updated on January 31, 2020 to screen recent records not 

captured in the original search

 We contacted subject matter experts and the manufacturer in an effort to obtain 

unpublished or other relevant data not included in the search and received 

permission to use one additional record: Legardy-Williams, 2020 (now published)
Evidence Retrieval (cont.)

Records were included if they presented data on the rVSVΔG-ZEBOV-GP Ebola 

virus vaccine and:

 Involved immunocompetent adults 18 years of age or older regardless of 

pregnancy status a

 Included data for intervention of interest (rVSVΔG-ZEBOV-GP, pre-exposure, single 

dose, any PFU) 

 Included data relevant to the outcome measures being assessed

 Reported primary data from comparative or single-arm studies; randomized 

control trials, prospective or retrospective cohort, case-control, cross-sectional 

studies b

a. Data from animal or in vitro studies or data from humans <18 years of age were excluded

b. Records that did not provide primary data (e.g. literature reviews or summaries, editorials, commentaries, opinions, clinical trial registries or protocols) 

and case reports or case studies were excluded
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)
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

1,3,5,6,7

,9,10,11,

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.
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Included in meta-analyses (RCT or NRS with comparator); Not included in meta-analyses (NRS, without comparator)