https://www.cdc.gov/vaccines/acip/recs/grade/ebola-vaccine-etr-H.pdf

ACIP Evidence to Recommendations Framework https://www.cdc.gov/vaccines/acip/recs/grade/ebola-vaccine-etr.html

The ETR framework was prepared and presented in February 2020.

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 the 

prevention Ebola virus disease (EVD)? 

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 EVD 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 

Comparison(s): No vaccine 

Outcomes: 











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)

Background: With case fatality rates of 70-90% when untreated, Ebola virus (species Zaire ebolavirus) is the most lethal of the 4 viruses that

cause EVD in humans. In addition, the virus is highly transmissible and can be found in all body fluids of an infected individual, including urine,

blood, salvia, sweat, feces, vomit, semen, and breastmilk. Death is rapid, usually occurring 7-10 days after symptom onset. In survivors, Ebola

virus (species Zaire ebolavirus) has been known to persist in immune-privileged sites, and in some instances, has resulted in continued disease

transmission and disease recrudescence. In addition, sequalae have been reported in EVD survivors including uveitis, arthralgia, myalgia, chronic 

abdominal pain and fatigue.Currently there is no FDA-approved treatment for EVD.

Ebola virus (species Zaire ebolavirus) is responsible for the majority of reported EVD outbreaks (18/28; 64%), including the largest EVD outbreak

in history (2014-2016 West Africa). Worldwide, outbreaks due to Ebola virus (species Zaire ebolavirus) have infected >31,000 persons and

resulted in >12,000 deaths. In total, 11 individuals infected with Ebola virus (species Zaire ebolavirus) were treated in the United States; all were

associated with the 2014-2016 West Africa outbreak. Of these 11 individuals, 9 were infected in West Africa; two (nurses) were infected in the

United States while caring for a returning traveler. Also, during both the 2014-2016 West Africa outbreak and the ongoing DRC outbreak,

additional individuals were repatriated to the United States following high-risk exposures to confirmed EVD patients, none tested positive for

Ebola virus. 

On August 1, 2018, an outbreak of EVD due to Ebola virus (species Zaire ebolavirus) was declared in eastern Democratic Republic of Congo

(DRC). Following an increase in EVD cases in eastern DRC and travel-associated cases in Uganda, the World Health Organization (WHO)

Emergency Committee declared the outbreak a public health emergency of international concern (PHEIC) on July 17, 2019. On February 12, 

2020, the committee unanimously re-affirmed that the outbreak still constitutes as a PHEIC. As of February 15, 2020, the ongoing outbreak in

DRC has infected >3000 persons and resulted in >2000 deaths.
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

https://www.cdc.gov/vaccines/acip/recs/grade/ebola-vaccine-etr-H.pdf

On December 19, 2019, the FDA approved rVSVΔG-ZEBOV-GP vaccine (ERVEBO®, Merck) for the prevention of disease caused by Zaire 

ebolavirus in individuals 18 years of age or older. The vaccine is a replication-competent, recombinant vesicular stomatitis virus-based vaccine

that protects only against Ebola virus (species Zaire ebolavirus). This vaccine is currently being administered in the eastern DRC EVD outbreak

using a post-exposure ring vaccination strategy in outbreak affected areas (DRC, Uganda) and pre-exposure vaccination in frontline workers in

DRC and high-risk surrounding countries (Uganda, Rwanda, South Sudan, and Burundi). The vaccine is currently available in the U.S. to

individuals at potential occupational risk through the PREPARE clinical trial.

CRITERIA WORK GROUP JUDGMENTS EVIDENCE ADDITIONAL INFORMATION

PROBLEM

Is the problem 

of public

health 

importance?

No Probably Uncertain Probably Yes Varies 

no yes 

X 

Ebola virus, species

Zaire Ebolavirus, is 

responsible for 18/28 

(64%) of EVD outbreaks

reported since 1976, 

including the two largest 

EVD outbreaks in history

(2014 West Africa

Outbreak, ongoing 

outbreak in the 

Democratic Republic of

Congo). In total, >31,000 

people have been

infected resulting in 

>12,000 deaths. 

Currently, there is no 

FDA-approved 

treatment for EVD. With 

the widespread use of

modern transportation,

a disease that was 

limited to remote

regions of Africa, is now

a global threat, as 

evidenced by the 2014

West Africa Outbreak. 

As such, domestic EVD

preparedness activities,

to include a vaccinated 

workforce that able to 

quickly respond to 
 

 

 

 

 

 

 

 

 

 

 

 

 Minimal Small Moderate Large Don’t know Varies 

 X 

https://www.cdc.gov/vaccines/acip/recs/grade/ebola-vaccine-etr-H.pdf

current and future

outbreaks, care for 

Ebola-infected patients

in the United States and 

carry out research to

better understand the

virus and develop new 

countermeasures is a 

public health priority. 

How 

substantial are

the desirable

anticipated 

effects?

Minimal Small Moderate Large Don’t 

know 

X 

Varies Only one study

evaluated using the 

GRADE process provided

data on efficacy. At the

participant level, the risk 

ratio (RR) was 0.04 with

a 95% confidence

interval (95% CI) of 

0.0001 – 0.74 [absolute

risk (AR) 5 fewer per

1,000; 95% CI 5 fewer to

1 fewer], demonstrating

a protective effect from

vaccination.

CRITERIA WORK GROUP JUDGMENTS RESEARCH EVIDENCE ADDITIONAL INFORMATION

How 

substantial are

the 

undesirable

anticipated 

effects?

Arthralgia is more

commonly reported among 

vaccinees (RR:2.55 for

RCTs). Severe arthralgia is

more commonly reported

among vaccinees (RR:6.40

for RCTs). Arthritis is more

commonly reported among 

vaccinees (RR: 1.80 for

RCTs). Pregnancy loss in

vaccinated women was not 

significantly higher than in 

non-vaccinated women 

(RR: 1.35). vaccine virus

BENEFITS & HARMS

(rVSV) was detected post-
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

https://www.cdc.gov/vaccines/acip/recs/grade/ebola-vaccine-etr-H.pdf

vaccination in blood, saliva,

urine, and synovial fluid by 

reverse transcriptase 

polymerase chain reaction 

(RT-PCR). Vaccine-related 

severe adverse events are 

rare 

Do the

desirable

effects

Favors Favors Favors both Favors Unclear 

intervention comparison neither 

X 

The documented

protective efficacy of the

vaccine against EVD is 

This falls under Situation 1 (Condition: When low 

quality evidence suggests benefit in a life-threatening 

situation (evidence regarding harms can be low

outweigh the considered to be of high or high) of the five paradigmatic situations in which

undesirable clinical benefit. Vaccine- a strong recommendation may be warranted

effects? related severe adverse despite low or very low confidence in effect

reactions were uncommon. estimates.

This, taken in consideration

with the high mortality rate Reference: Andrews JC, et al. GRADE guidelines: 15.

in infected individuals, high Going from evidence to recommendationtransmissibility of the virus, determinants of a recommendation’s direction and 

disease sequalae, and lack strength. J Clin Epidemiol. 2013 Jul; 66(7):726-35).

of an FDA-approved 

treatment factor into the

assessment that the

desirable effects of

vaccination outweigh the 

undesirable effects.

What is the Effectiveness of the intervention One study evaluated using “Low” and “very low” certainty of evidence for

overall No the GRADE process arthralgia, severe arthralgia, and arthritis may be

certainty of included 4 3 2 1 

studies Very low Low Moderate High provided data on efficacy. due to variability between studies in the definition

this evidence X At the participant level the of these outcomes, methodology used to diagnosis

for the critical Safety of the intervention overall certainty in the these outcomes, availability of specialized 

outcomes? No 

included 4 3 2 1 

studies Very low Low Moderate High 

X 

evidence for effectiveness

is “moderate”. 

The overall certainty in the

evidence is “very low” for 

the safety outcomes based

on the lowest of the critical

outcomes. The certainty of

evidence for arthralgia 0-42 

days after vaccination was

care/radiographic imaging, and timing when these

outcomes were assessed.

Low certainty for severe adverse events was low

due to extraction of vaccinated-arm data only, thus 

rendering the data observational. 
 

 

 

 

 

 

 

 

 

 

 

 

https://www.cdc.gov/vaccines/acip/recs/grade/ebola-vaccine-etr-H.pdf

”very low” for RCTs and

observational studies.

Certainty of evidence for

severe arthralgia was “low”

for RCTS and “very low” for 

observational studies.

Certainty of evidence of

arthritis (0-56 days after 

vaccination) was “low” for

RCTs and “very low” for

observational studies.

Certainty of evidence for

vaccine-related adverse 

pregnancy outcomes was

“very low” for 

observational studies.

Certainty of evidence for

severe adverse events 

(SAE)was “low” for 

observational studies.

Vaccine related SAEs were 

rare. No data were 

available on vaccine virus 

transmissibility to nonvaccinated persons or 

animals, as such viral

dissemination and

shedding were used as 

indirect surrogates. The 

certainty of evidence for

transmissibility of vaccine

virus is “very low” for 

observational studies.
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

https://www.cdc.gov/vaccines/acip/recs/grade/ebola-vaccine-etr-H.pdf VALUES

Does the

target 

population feel

that the 

desirable

effects are

large relative 

to undesirable 

effects?

No Probably Uncertain Probably Yes Varies 

no Yes 

X 

No Knowledge, Attitudes,

and Practices surveys have 

been conducted amongst

our 3 populations of

interest as it pertains to the 

rVSVΔG-ZEBOV-GP vaccine.

Although exact numbers

are unavailable, BSL-4 

laboratorians and support 

staff, healthcare personnel1 

from the federallydesignated Ebola

Treatment Centers, and 

individuals responding to 

an EVD outbreak have

participated in in a clinical 

trial offering the vaccine

which would suggest at 

least some within these

groups feel that the 

desirable effects are large

relative to undesirable

effects. Given that 10/11

individuals infected with 

EBOV and treated in the 

United States were either

responding to an EVD

outbreak and/or were 

healthcare workers, work

group members think that 

persons responding to an 

EVD outbreak and HCP at 

federally designated Ebola

Treatment Centers would

feel that the desirable

effects are relative to

undesirable effects. For

BSL-4 laboratorians and 

support staff, response to 

vaccination has been
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

https://www.cdc.gov/vaccines/acip/recs/grade/ebola-vaccine-etr-H.pdf

mixed. Some have enrolled

in a clinical trial offering

the vaccine (PREPARE).

Others were unable to

enroll in PREPARE due to

logistical challenges but

expressed interest in 

accessing the licensed 

vaccine when it is available

outside of the three

PREPARE clinical trial sites.

In addition, there are 

anecdotal reports of some

BSL-4 laboratorians and

support staff declining

vaccination because the

additional level of

protection afforded by

vaccination, in the

backdrop of strict biosafety

measures already in place

in BSL-4 laboratories, was 

considered to be minimal

compared to the potential

undesirable effects of

vaccination.

CRITERIA WORK GROUP JUDGMENTS RESEARCH EVIDENCE ADDITIONAL INFORMATION

Is there

important

uncertainty

about or

variability in

how much

people value 

the main

outcomes?

Possibly Probably no 

Important important important No important No known 

uncertainty uncertainty uncertainty uncertainty or undesirable 

or variability or variability or variability variability outcomes 

X 

Given the high mortality

associated with EVD, the

lack of an FDA-approved 

treatment, the high

transmissibility of the virus,

this vaccine’s

demonstrated efficacy in 

preventing EVD, and their 

interest and participation 

in a clinical trial offering

vaccination, we believe

that most individuals 

within our three 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

https://www.cdc.gov/vaccines/acip/recs/grade/ebola-vaccine-etr-H.pdf

populations of interest 

would be interested in 

being vaccinated. Although

the response to vaccination 

amongst BSL-4 

laboratorians and support

staff have been mixed, the 

work group thinks that 

most in this population will 

feel that desirable effects

are large relative to the 

undesirable effects.

ACCEPTABILITY

Is the

intervention 

acceptable to

key

stakeholders?

No Probably Uncertain Probably Yes Varies 

no yes 

X 

No Knowledge, Attitudes,

and Practices (KAP) surveys

have been conducted

amongst US healthcare

workers related to the 

rVSVΔG-ZEBOV-GP. 

However, individuals within 

the 3 populations at 

potential occupational risk

of exposure to the virus

have enrolled in the 

ongoing PREPARE trial and

have received the vaccine.

Given the high mortality

associated with EVD, the

Stakeholders include 1) Individuals responding to

an outbreak of EVD; 2) healthcare workers and

support staff involved in the care and transport of

confirmed EVD patients at the ten regional Special

Pathogen Centers in the United States;

3)Laboratorians and support staff working at the

ten biosafety level 4 (BSL4) laboratories in the 

United States 4) administrators at public health

institutions involved in EVD response activities

5)administrators at non-governmental

organizations involved in EVD response activities 6)

administrators at Special Pathogen Centers 7)

administrators at BSL4 laboratories.

lack of an FDA-approved 

treatment, the high 

transmissibility of the virus,

and this vaccine’s 

demonstrated efficacy,

acceptability is expected to

continue despite the 

moderate anticipated

undesirable effects. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

X 

https://www.cdc.gov/vaccines/acip/recs/grade/ebola-vaccine-etr-H.pdf RESOURCE USE

Is the

intervention a 

reasonable

and efficient 

allocation of

resources? 

No Probably Uncertain Probably Yes 

no yes 

X 

A cost effectiveness

evaluation was not 

performed because this

vaccine is intended for use

in emergency response and 

preparedness scenarios in 

limited populations, and

not as routine vaccination 

in the general population.

At this time in the U.S., the 

vaccine will be stored and 

made available through the

US Government.

FEASIBILITY

Is the

intervention 

feasible to

implement?

No Probably Uncertain Probably Yes Varies 

no yes 

X 

As it appears now, no 

licensed vaccine will be

available until Q3/Q4 of

2020. The vaccine is

currently available through

the PREPARE clinical trial.

Discussions are ongoing on 

mechanisms to allow for

limited quantities of 

investigational-labeled 

vaccine to be made

available for ACIPThe vaccine has stringent cold chain requirements

(-60 to -80C).

recommended populations

in the interim period

between ACIP

recommendations and

availability of licensed 

product outside the setting 

of a clinical trial.

Balance of Undesirable Undesirable The balance between Desirable Desirable There is insufficient

consequences consequences

clearly outweigh 

consequences

probably outweigh 

desirable and

undesirable

consequences

probably outweigh 

consequences

clearly outweigh 

evidence to 

determine the

desirable desirable consequences undesirable undesirable balance of

consequences consequences is closely balanced or consequences consequences consequences

in most settings in most settings uncertain in most settings in most settings
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

https://www.cdc.gov/vaccines/acip/recs/grade/ebola-vaccine-etr-H.pdf

Is there sufficient information to move forward with a recommendation?

Yes x No 

Policy options for

ACIP consideration

ACIP does not recommend the

intervention* 

*Intervention may be used within

FDA licensed indications

ACIP recommends the intervention for

individuals based on shared clinical

decision-making

ACIP recommends the intervention

X 

Draft

recommendation

(text)

Please provide the draft recommendations proposed to ACIP. 

1. Pre-exposure vaccination with rVSVΔG-ZEBOV-GP vaccine is recommended for adults 18 years of age or

older in the U.S. population who are responding to an outbreak of EVD due to Ebola virus (species Zaire 

ebolavirus)

2. Pre-exposure vaccination with rVSVΔG-ZEBOV-GP vaccine is recommended for adults 18 years of age or

older who work as healthcare personnel1 at a federally-designated Ebola Treatment Center in the United 

States 

3. Pre-exposure vaccination with rVSVΔG-ZEBOV-GP vaccine is recommended for adults 18 years of age or

older who work as laboratorians and support staff at biosafety-level 4 facilities in the U.S. who are at

potential risk for occupational exposure to Ebola virus (species Zaire ebolavirus)

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/healthcare-personnel/index.html
 

 

 

 

 

 

 

 

https://www.cdc.gov/vaccines/acip/recs/grade/ebola-vaccine-etr-H.pdf

Additional rVSVΔG-ZEBOV Ebola vaccine is currently no commercially available in the U.S. The vaccine will be stored and made

considerations available for U.S. civilians through the US Government in accordance with ACIP recommendations upon receipt of request.

(optional)

Final deliberation and decision by the ACIP 

Final ACIP

recommendation

ACIP does not recommend the

intervention* 

*Intervention may be used within FDA

licensed indications 

ACIP recommends the intervention for

individuals based on shared clinical

decision-making

ACIP recommends the intervention

x 

Additional ACIP

considerations 

Pre-exposure vaccination with rVSVΔG-ZEBOV-GP vaccine is recommended for adults 18 years of age or older in the

United States population who are at potential risk of exposure to Ebola vaccine (species Zaire ebolavirus) because they:

• Are responding to an outbreak of EVD; or

• Work as healthcare personnel at a federally-designated Ebola Treatment Center in the United States; or

• Work as laboratorians or other staff at biosafety-level 4 facilities in the United States.