Certain laboratorians and health care personnel can be exposed to orthopoxviruses
through occupational activities. Because orthopoxvirus infections resulting from occupational
exposures can be serious, the Advisory Committee on Immunization Practices (ACIP)
has continued to recommend preexposure vaccination for these persons since 1980 (
1
), when smallpox was eradicated (
2
). In 2015, ACIP made recommendations for the use of ACAM2000, the only orthopoxvirus
vaccine available in the United States at that time (
3
). During 2020–2021, ACIP considered evidence for use of JYNNEOS, a replication-deficient
Vaccinia virus vaccine, as an alternative to ACAM2000. In November 2021, ACIP unanimously
voted in favor of JYNNEOS as an alternative to ACAM2000 for primary vaccination and
booster doses. With these recommendations for use of JYNNEOS, two vaccines (ACAM2000
and JYNNEOS) are now available and recommended for preexposure prophylaxis against
orthopoxvirus infection among persons at risk for such exposures.
Orthopoxviruses are large, double-stranded DNA viruses (Genus Orthopoxvirus, Family
Poxviridae) that comprise multiple species, including Variola virus, Vaccinia virus,
Monkeypox virus, Cowpox virus, and newly discovered species (e.g., Akhmeta virus and
Alaskapox virus) (
4
). Infection with an orthopoxvirus or immunization with an orthopoxvirus vaccine lends
immunologic cross-protection against other viruses in the genus (
3
). Until 1971, children in the United States received an orthopoxvirus vaccine (to
prevent smallpox) as part of their routine childhood vaccines. However, with the World
Health Organization (WHO) declaration of the eradication of smallpox (the infection
caused by Variola virus) in 1980 (
2
), recommendations for routine vaccinations ended worldwide.
A small subset of persons in the United States continues to receive orthopoxvirus
vaccination (
3
): persons at occupational risk for exposure to orthopoxvirus infections and certain
U.S. military personnel. The first group (those with occupational risk for exposure)
are within the purview of ACIP and the focus of this report. Regular booster doses
are recommended for persons with ongoing occupational risk for exposure to orthopoxvirus
infections. Designated public health and health care worker response teams approved
by public health authorities should receive booster vaccination only at the time of
an event, rather than at regular intervals.*
Poxviruses are increasingly being used in a wide range of biomedical research (
3
). Vaccinia virus is the most frequently studied poxvirus and serves as the prototype
of the orthopoxvirus genus. This orthopoxvirus is used in basic virologic research,
and because of its ability to serve as a vector for the expression of foreign genetic
material, it is often used as an immunology tool and potential vaccine vector. Vaccinia
virus is considered one of the less virulent orthopoxviruses, and possibly because
of this perception, many laboratorians who work with this virus do not receive preexposure
prophylaxis. CDC has received reports of occupational exposures to Vaccinia virus
over the years and in some cases, morbidity has not been insignificant (
5
,
6
) In nearly all cases, infections with Vaccinia virus occurred in persons who were
unvaccinated or previously vaccinated but not up to date with recommended booster
doses.
In addition to less virulent viruses like Vaccinia virus, some researchers work with
more virulent orthopoxviruses, including Variola virus (in some CDC laboratories)
and Monkeypox virus. ACIP has historically recommended more frequent booster vaccination
doses for persons working with more virulent orthopoxviruses than for those working
with less virulent orthopoxviruses (
3
).
Replication-competent poxvirus strains can cause clinical infection in humans as well
as produce infectious virus that can be transmitted to others (
3
). Replication-deficient poxvirus strains, including modified vaccinia Ankara (MVA),
TROVAC, and ALVAC, do not produce infectious virus in humans, and therefore do not
cause clinical infection; as such, replication-deficient poxvirus strains pose a substantially
lower risk of adverse events compared with replication-competent strains. During 2015–2019,
ACAM2000 was the only orthopoxvirus vaccine licensed by the Food and Drug Administration
(FDA); ACIP recommendations for use of ACAM2000 in the United States were published
in 2015 (
3
). ACAM2000 is a replication-competent Vaccinia virus vaccine derived from a plaque-purified
clone of the same New York City Board of Health strain that was used to manufacture
Dryvax vaccine, one of the vaccines used in the eradication of smallpox. Because ACAM2000
is replication-competent, there is a risk for serious adverse events (e.g., progressive
vaccinia and eczema vaccinatum) with it; myopericarditis also occurs with ACAM2000
(estimated rate of 5.7 per 1,000 primary vaccinees based on clinical trial data),
but the underlying mechanism is unknown (
7
,
8
).
In 2019, FDA licensed JYNNEOS, a replication-deficient MVA vaccine, for prevention
of smallpox or monkeypox disease in adults aged ≥18 years determined to be at high
risk for infection with these viruses. JYNNEOS is administered by subcutaneous injection
as a 2-dose series delivered 28 days apart. There is no major cutaneous reaction,
also known as a “take” (a vaccine site lesion often used as a marker of successful
vaccination with replication-competent vaccines such as ACAM2000), following vaccination
with JYNNEOS and consequently no risk for inadvertent inoculation or autoinoculation.
The effectiveness of JYNNEOS was inferred from the immunogenicity of JYNNEOS in clinical
studies and from efficacy data from animal challenge studies. Occurrences of serious
adverse events are expected to be minimal because JYNNEOS is a replication-deficient
virus vaccine. However, because the mechanism for myopericarditis following receipt
of ACAM2000 is thought to be an immune-mediated phenomenon, it is not known whether
the antigen or antigens that precipitate autoantibodies are present in JYNNEOS as
well. ACIP began considering discussing the data for JYNNEOS in February 2020. This
report describes the ACIP recommendations for the use of JYNNEOS for preexposure prophylaxis
in persons at occupational risk for exposure to orthopoxviruses.
Methods
During January 2020–November 2021, the ACIP Orthopoxvirus Work Group participated
in monthly or bimonthly teleconferences to consider the evidence for five questions:
1) should JYNNEOS be recommended for research laboratory personnel, clinical laboratory
personnel performing diagnostic testing for orthopoxviruses, and designated response
team members at risk for occupational exposure to orthopoxviruses; 2) should JYNNEOS
be recommended for health care personnel who administer ACAM2000 or care for patients
infected with replication-competent orthopoxviruses; 3) should persons who are at
ongoing risk for occupational exposure to more virulent orthopoxviruses such as Variola
virus or Monkeypox virus receive a booster dose of JYNNEOS every 2 years after the
primary JYNNEOS series; 4) should persons who are at ongoing risk for occupational
exposure to less virulent replication-competent orthopoxviruses such as Vaccinia virus
or Cowpox virus receive a booster dose of JYNNEOS at least every 10 years after the
primary JYNNEOS series; and 5) should persons who are at ongoing risk for occupational
exposure to orthopoxviruses and who received an ACAM2000 primary vaccination have
the option to receive a booster dose of JYNNEOS as an alternative to a booster dose
of ACAM2000. The Work Group comprised experts in diverse disciplines, including laboratory,
public health, infection control, preparedness, and various clinical specialties (e.g.,
infectious disease, obstetrics, and occupational health). Federal partners represented
on the Work Group included FDA, the National Institutes of Health, the U.S. Department
of Defense, and the U.S. Department of Health and Human Services-Biomedical Advanced
Research and Development Authority. CDC contributors also joined Work Group meetings
with subject matter expertise in orthopoxviruses, regulatory affairs, laboratory diagnostic
testing, vaccine adverse events, and drug services. Data collected, analyzed, and
prepared by the Work Group were deliberated by ACIP during four public meetings.
Subject matter experts performed a systematic review and metaanalysis of the published
literature on August 12, 2020, to inform the recommendations; the review was not limited
by date or language. The Work Group used a modified Grading of Recommendations Assessment,
Development and Evaluation (GRADE) approach to determine the certainty of evidence
rated on a scale of 1 (high certainty) to 4 (very low certainty) for the following
desirable and undesirable outcomes deemed critical for decision-making: prevention
of disease, incidence of serious adverse events, and incidence of myopericarditis;
prevention of disease was defined as prevention of an orthopoxvirus infection. Although
no level of antibody protection for orthopoxviruses has been established, the detection
of neutralizing antibodies after JYNNEOS is an indirect measure of protection (i.e.,
immunogenicity). Immunogenicity that peaks 2 weeks after completion of the 2-dose
series (i.e., 6 weeks after the first vaccine in the 2-dose series) is called primary
immunogenicity. Within the evidence to recommendations (EtR) framework, ACIP considered
the importance of orthopoxvirus infection as a public health problem; the benefits
and harms (including the graded evidence); the target populations’ values and preferences;
and issues of resource use, acceptability to stakeholders, feasibility of implementation,
and anticipated impact on health equity.
Summary of Findings and Rationale for Recommendations
For the first and second questions, regarding recommendation for JYNNEOS as an alternative
to ACAM2000 for primary vaccination, the systematic review identified three randomized
controlled studies and 15 observational studies including a total of 5,775 subjects.
After considering geometric mean titers and seroconversion data together, the Work
Group had moderate (level 2) certainty that JYNNEOS provides a small increase in disease
prevention compared with that provided by ACAM2000.
†
The Work Group estimated with low (level 3) certainty that fewer serious adverse events
occur following the JYNNEOS primary series compared with ACAM2000 primary vaccination,
and that fewer events of myopericarditis occur after JYNNEOS primary series than after
ACAM2000 primary vaccination. Based on the results from the GRADE assessment and EtR
framework,
§
ACIP unanimously voted in favor of the JYNNEOS vaccine as an alternative to ACAM2000
for primary vaccination.
To address the third and fourth questions, regarding booster doses, the systematic
review identified one randomized controlled trial and 17 observational studies that
included a total of 6,417 subjects. After considering geometric mean titer and seroconversion
rate together, the Work Group estimated with very low (level 4) certainty that a small
increase in disease prevention occurs after JYNNEOS booster versus the JYNNEOS primary
series only.
¶
The Work Group estimated with very low (level 4) certainty that fewer serious adverse
events occur after a JYNNEOS booster administered following completion of the JYNNEOS
primary series compared with the JYNNEOS primary series (i.e., no booster dose). No
myopericarditis events were recorded in either the intervention or comparison; for
this reason, the effect was not estimable and the Work Group had very low (level 4)
certainty that myopericarditis does not occur after JYNNEOS boosters because of inadequate
sample size to detect rare events. The ACIP unanimously voted in favor of the JYNNEOS
booster vaccine after the 2-dose JYNNEOS primary series. ACIP recommended that the
JYNNEOS booster dose be administered every 2 years to persons working with more virulent
orthopoxviruses and every 10 years to persons working with less virulent orthopoxviruses.
For the fifth question, regarding providing the option of transitioning to JYNNEOS
for a booster dose in persons who had received primary vaccination with ACAM2000,
the systematic review identified one randomized controlled trial and five observational
studies that included a total of 435 subjects. A total of 82% of subjects seroconverted
when given JYNNEOS booster, with very low (level 4) certainty in that estimate. The
Work Group estimated, with low (level 3) certainty, fewer serious adverse events occurred
after the JYNNEOS booster than after the ACAM2000 booster in persons previously vaccinated
with ACAM2000** and that fewer myopericarditis events occurred after a JYNNEOS booster
than after an ACAM2000 booster in persons who received ACAM2000 as the primary vaccine
(very low [level 3] certainty). Based on the results from the GRADE methodology and
findings within the EtR framework,
††
ACIP unanimously voted in favor of recommending JYNNEOS boosters as an alternative
to ACAM2000 boosters in persons who received ACAM2000 as the primary vaccine.
Recommendations
Research laboratory personnel,
§§
clinical laboratory personnel performing diagnostic testing for orthopoxviruses,
¶¶
designated response team members,*** and health care personnel who administer ACAM2000
(Smallpox [Vaccinia] Vaccine, Live)
†††
or care for patients infected with orthopoxviruses
§§§
are the persons to whom these recommendations apply (Table 1). For laboratory personnel
and designated response team members, ACIP recommends use of JYNNEOS for primary vaccination
as an alternative to ACAM2000. For health care personnel who administer ACAM2000 or
care for patients infected with orthopoxviruses, ACIP recommends use of JYNNEOS (as
an alternative to ACAM2000), based on shared clinical decision-making. In addition,
persons who received the 2-dose JYNNEOS primary series and who are at ongoing risk
¶¶¶
for occupational exposure to more virulent orthopoxvirus e.g., Variola virus and Monkeypox
virus), should receive a booster dose of JYNNEOS every 2 years after the primary JYNNEOS
series; persons who receive the 2-dose JYNNEOS primary series and who are at ongoing
risk for occupational exposure to less virulent orthopoxviruses, (e.g., Vaccinia virus
or Cowpox virus), should receive booster doses of JYNNEOS at least every 10 years
after the primary JYNNEOS series. ACIP also recommends that persons who received an
ACAM2000 primary vaccination and who are at ongoing risk for occupational exposure
to orthopoxviruses may receive a booster dose of JYNNEOS as an alternative to a booster
dose of ACAM2000.
TABLE 1
Recommendations for ACAM2000 and JYNNEOS vaccines for persons at occupational risk
for exposure to orthopoxviruses — Advisory Committee of Immunization Practices, United
States, 2022
Recommendations
Vaccine product
ACAM2000
JYNNEOS
Who should receive the vaccine?
Persons at risk for occupational exposure to orthopoxviruses*
Who should be offered the vaccine?
Persons who administer ACAM2000 or care for patients with infection with replication-competent
viruses
Populations for whom booster vaccination is recommended at specific intervals
Persons who are at ongoing risk† for occupational exposure to orthopoxviruses
Booster frequency§
Persons working with more virulent orthopoxviruses (e.g., Variola virus or Monkeypox
virus)
Every 3 years
Every 2 years
Persons working with less virulent orthopoxviruses (e.g., Vaccinia virus or Cowpox
virus)
At least every 10 years
* Research laboratory personnel, clinical laboratory personnel performing diagnostic
testing for orthopoxviruses, designated response team members, and health care personnel
who administer ACAM2000 (Smallpox [Vaccinia] Vaccine, Live) or care for patients infected
with orthopoxviruses.
† Ongoing risk due to occupational work performed; response personnel are not considered
at “sustained risk” for orthopoxvirus infections.
§ Booster doses are recommended for response personnel only once an event is identified.
Clinical Guidance
Considerations in Choosing JYNNEOS or ACAM2000 for Primary Vaccination
JYNNEOS involves a replication-deficient virus and has fewer contraindications, no
risk for inadvertent inoculation and autoinoculation, and is associated with fewer
serious adverse events compared with ACAM2000 (Table 2). In addition, most health
care providers have experience with and are comfortable providing vaccines by subcutaneous
administration, the route by which JYNNEOS is administered. ACAM2000, on the other
hand, is administered percutaneously through a multiple puncture (scarification) technique,
through 15 jabs with a stainless steel bifurcated needle that has been dipped into
the reconstituted vaccine, a vaccination technique that is unique to orthopoxvirus
vaccinations (
3
). JYNNEOS involves 2 vaccine doses 28 days apart and vaccine protection is not conferred
until 2 weeks after receipt of the second dose; ACAM2000 involves 1 dose of vaccine
and peak vaccine protection is conferred within 28 days.
TABLE 2
Distinctions between ACAM2000 and JYNNEOS that might facilitate decision-making among
vaccinees at risk for orthopoxvirus infections — United States, 2022
Characteristic
Vaccine product
ACAM2000*
JYNNEOS
Vaccine virus
Replication-competent vaccinia virus
Replication-deficient modified vaccinia Ankara
“Take” following vaccination†
Yes
No
Risk for inadvertent inoculation and autoinoculation
Yes
No
Risk for serious adverse event
Yes
No significant events identified during clinical trials
Risk for cardiac adverse events
Myopericarditis in 5.7 per 1,000 primary vaccinees
Clinical trial data limited in evaluating this outcome; however, no significant events
in data abstracted from single study arms§
Assessment of effectiveness
FDA assessed by comparing immunologic response and take rates to Dryvax*
FDA assessed by comparing immunologic response to ACAM2000 and animal studies
Administration
Percutaneously using a bifurcated needle by multiple puncture (scarification) technique,¶
single dose
Subcutaneously, 2 doses 28 days apart
Abbreviation: FDA = Food and Drug Administration.
*Both ACAM2000 and Dryvax are derived from the New York City Board of Health strain
of vaccinia; ACAM2000 is a second generation smallpox vaccine derived from a clone
of Dryvax, purified, and produced using modern cell culture technology.
† A “take” is postvaccination lesion often used as a marker of successful vaccination
after ACAM2000.
§ Because JYNNEOS is a replication-deficient virus vaccine, serious adverse events
are believed to be fewer. However, the mechanism of myopericarditis in persons who
receive ACAM2000 is poorly understood; for this reason, it is unknown whether persons
who receive JYNNEOS might experience myopericarditis.
¶
https://www.fda.gov/media/75792/download
For those working with more virulent orthopoxviruses, the frequency of booster doses
also differs: ACAM2000 boosters are recommended every 3 years, whereas JYNNEOS boosters
are recommended every 2 years. After successful administration of vaccine, ACAM2000
produces a take containing infectious vaccinia virus capable of transmission through
autoinoculation and inadvertent inoculation of close contacts of vaccinees; JYNNEOS
does not produce a take. Some persons might prefer receiving ACAM2000 because the
vaccine is a derivative of Dryvax, which was used successfully in eradicating smallpox,
a clear demonstration of its effectiveness in preventing disease.
A robust antibody response following a single dose of JYNNEOS has been observed in
clinical trials (
9
). In addition, limited data from animal model studies indicate that a single dose
of JYNNEOS might provide protection for some persons against orthopoxvirus infection
when administered before and closely after (1 day) viral challenge (
10
,
11
).
Considerations for Transitioning from the Use of One Orthopoxvirus Vaccine to the
Other for Booster Doses
Persons who previously received ACAM2000 should decide before their next booster dose
whether to receive ACAM2000 or JYNNEOS. Persons who transition to receiving JYNNEOS
boosters are expected to continue receiving JYNNEOS boosters and to not revert to
ACAM2000; in addition, the frequency of booster doses should correspond to the vaccine
used for boosters. For example, persons who previously received ACAM2000 every 3 years
because of work with more virulent orthopoxviruses might decide to change to JYNNEOS
when their next booster dose is due; in these cases, subsequent JYNNEOS booster doses
should be administered every 2 years.
Fewer persons are expected to transition from JYNNEOS to ACAM2000; however, if those
situations arise, they should be handled on a case-by-case basis. If this transition
is approved by public health authorities, vaccinees should be advised that the expectation
is that they will receive ACAM2000 for all future vaccine booster doses.
Contraindications To and Precautions Associated with Vaccinations to Prevent Orthopoxvirus
Infections
JYNNEOS is contraindicated in persons with a serious allergy to a vaccine component
(Table 3). Primary vaccination with ACAM2000 is contraindicated in persons with the
following conditions: serious allergy to a vaccine component, history of atopic dermatitis
or other exfoliative skin condition,**** an immunocompromising condition (e.g., due
to a disease or therapeutics),
††††
pregnancy, breastfeeding, and known underlying heart disease (e.g., coronary artery
disease or cardiomyopathy). ACAM2000 vaccination is also contraindicated if the vaccine
recipient cannot sufficiently isolate from household contacts who have a history of
atopic dermatitis or other active exfoliative skin condition, an immunocompromising
condition, or who are pregnant or aged <1 year; household contacts include persons
with prolonged intimate contact with the potential vaccine recipient and others who
might have direct contact with the vaccination site or with potentially contaminated
materials (e.g., clothing or vaccination site dressings). Availability of JYNNEOS
provides opportunities for vaccinating persons in situations where ACAM2000 might
be contraindicated.
TABLE 3
Contraindication to administration of ACAM2000 and JYNNEOS to recipients or their
household contacts with certain conditions — United States, 2022
Clinical characteristic
Contraindication to receipt of ACAM2000
Contraindication to receipt of JYNNEOS
Vaccine recipient with condition
Household contact with condition*
Primary vaccination
Revaccination
History or presence of atopic dermatitis
Y
Y
Y
—
Other active exfoliative skin conditions†
Y
Y
Y
—
Immunosuppression§
Y
Y
Y
—
Pregnancy¶
Y
Y
Y
—
Age <1 year**
Y
Y
Y
—
Breastfeeding††
Y
Y
—
—
Serious vaccine component allergy
Y
Y
—
Y
Known underlying heart disease (e.g., coronary artery disease or cardiomyopathy)
Y
Y
—
—
≥3 known major cardiac risk factors§§
Y
—
—
—
Abbreviation: Y = yes.
* Household contacts include persons with prolonged intimate contact with the potential
vaccinee (e.g., sexual contacts) and others who might have direct contact with the
vaccination site or with potentially contaminated materials (e.g., dressings or clothing).
JYNNEOS is a replication-deficient vaccine and therefore should not present a risk
of transmission to household contacts.
† Conditions include eczema, burns, impetigo, varicella-zoster, herpes, severe acne,
severe diaper dermatitis with extensive areas of denuded skin, psoriasis, or Darier
disease (keratosis follicularis). Studies evaluating JYNNEOS in persons with atopic
dermatitis have demonstrated immunogenicity in eliciting a neutralizing antibody response
and did not reveal any significant safety concerns.
§ Conditions include HIV; AIDS; leukemia; lymphoma; generalized malignancy; solid
organ transplantation; therapy with alkylating agents, antimetabolites, radiation,
tumor necrosis factor inhibitors, or high-dose corticosteroids; being a recipient
of a hematopoietic stem cell transplant <24 months ago or ≥24 months ago but with
graft-versus-host disease or disease relapse; or having autoimmune disease with immunodeficiency
as a clinical component. Immunocompromised persons, including those receiving immunosuppressive
therapy, may have a diminished immune response to JYNNEOS because of their immunocompromised
status.
¶ Available human data on JYNNEOS administered to pregnant women are insufficient
to determine vaccine-associated risks in pregnancy. However, animal models, including
rats and rabbits, have shown no evidence of harm to a developing fetus.
** ACAM2000 is contraindicated in infants aged <1 year. Caution should be used when
considering the administration of ACAM2000 or JYNNEOS to children and adolescents
aged <18 years. JYNNEOS is not licensed for persons aged <18 years and has not been
rigorously evaluated in this population.
†† The safety and efficacy of JYNNEOS has not been evaluated in breastfeeding women.
It is not known whether JYNNEOS is excreted in human milk and data are not available
to assess the impact of JYNNEOS on milk production or safety of JYNNEOS in breastfed
infants. However, JYNNEOS vaccine is replication-deficient and therefore should not
present a risk of transmission to breastfed infants. Caution should be used when considering
the administration of JYNNEOS to breastfeeding women.
§§ Major cardiac risk factors include hypertension, diabetes, hypercholesterolemia,
heart disease at age ≤50 years in a first-degree relative, and smoking. Clinical studies
have not detected an increased risk of myopericarditis in recipients of JYNNEOS. Persons
with underlying heart disease or ≥3 major cardiac risk factors should be counseled
on the theoretical risk of myopericarditis given the uncertain etiology of myopericarditis
associated with replication-competent smallpox vaccines.
Because of the documented risk for myocarditis after receipt of both ACAM2000 and
mRNA COVID-19 vaccines (
12
) and the unknown risk for myocarditis after JYNNEOS, persons might consider waiting
4 weeks after orthopoxvirus vaccination (either JYNNEOS or ACAM2000) before receiving
an mRNA COVID-19 vaccine, particularly adolescent or young adult males. However, if
an orthopoxvirus vaccine is recommended for prophylaxis in the setting of an outbreak,
administration of orthopoxvirus vaccine should not be delayed because of recent receipt
of an mRNA COVID-19 vaccine. No minimum interval between mRNA COVID-19 vaccination
and orthopoxvirus vaccination is necessary.
Vaccinations Administered to Special Populations
Persons with atopic dermatitis, eczema, or other exfoliative skin conditions. Studies
evaluating JYNNEOS in persons with atopic dermatitis have demonstrated immunogenicity
in eliciting a neutralizing antibody response. No safety signals were revealed. However,
persons with these conditions might be at increased risk for severe disease if an
occupational infection occurs despite vaccination (
13
).
Persons with immunocompromising conditions. JYNNEOS is safe to administer to persons
with immunocompromising conditions. However, such persons might be at increased risk
for severe disease if an occupational infection occurs, despite vaccination. In addition,
persons with immunocompromising conditions might be less likely to mount an effective
response after any vaccination,
§§§§
including after JYNNEOS; the risk/benefit ratio should be considered along with whether
it is considered imperative to vaccinate an immunocompromised person.
Pregnant women. Available human data on JYNNEOS administered to pregnant women are
insufficient to determine vaccine-associated risks in pregnancy. However, animal models,
including rats and rabbits, have shown no evidence of harm to a developing fetus.
Breastfeeding women. The safety and efficacy of JYNNEOS has not been evaluated in
breastfeeding women. It is not known whether JYNNEOS is excreted in human milk. Data
are not available to assess the impact of JYNNEOS on milk production or the safety
of JYNNEOS in breastfed infants. However, because JYNNEOS vaccine is replication-deficient,
it likely does not present a risk of transmission to breastfed infants and can be
administered to women who are breastfeeding if vaccination is critical.
Children and adolescents aged <18 years. Although occupational exposure to orthopoxviruses
is unlikely in persons aged <18 years, it is important to note that JYNNEOS is not
licensed for persons aged <18 years and has not been rigorously evaluated in this
population. Public health authorities should be consulted if JYNNEOS is being considered
for children and adolescents aged <18 years. Administration of ACAM2000 to infants
aged <1 year is contraindicated. Caution should be used when considering the administration
of ACAM2000 or JYNNEOS to children and adolescents aged <18 years.
Persons with multiple cardiac risk factors. Major cardiac risk factors include hypertension,
diabetes, hypercholesterolemia, heart disease at age ≤50 years in a first-degree relative,
and smoking and the presence of three or more of these factors are contraindications
to primary vaccination with ACAM2000. Clinical studies have not detected an increased
risk for myopericarditis in recipients of JYNNEOS. Persons with underlying heart disease
or three or more major cardiac risk factors should be counseled about the theoretical
risk for myopericarditis following vaccination with JYNNEOS given the uncertain etiology
of myopericarditis associated with replication-competent smallpox vaccines such as
ACAM2000.
Reporting of Adverse Events
Adverse events following vaccination can be reported to the Vaccine Adverse Event
Reporting System (VAERS). Reporting is encouraged for any clinically significant adverse
event, even if it is uncertain whether the vaccine caused the event. Information on
how to submit a report to VAERS is available at https://vaers.hhs.gov/index.html or
by telephone at 1-800-822-7967.
Peak Antibody Response, Confirming Effective Vaccination in Immunocompromised Persons,
and Correlate of Protection After Vaccination with JYNNEOS
Peak antibody response is achieved 2 weeks after receipt of the second dose of the
2-dose JYNNEOS vaccination series (
9
). Evidence of a take is often used as a marker of successful vaccination after ACAM2000
(
3
). Because JYNNEOS is a replication-deficient vaccine, vaccination with JYNNEOS does
not produce a take; however, clinical trials have demonstrated high rates of seroconversion
after the 2-dose series. Therefore, effective vaccination can be assumed for immunocompetent
persons. Routine antibody titer testing (to confirm successful vaccination) following
vaccination with JYNNEOS is not recommended for immunocompetent persons. If the decision
is made to vaccinate immunocompromised persons, titer testing by CDC might be considered
on a case-by-case basis; clinicians considering vaccinating immunocompromised persons
should consult public health authorities. Because a correlate of protection has not
been established and there is no known antibody titer level that will ensure protection,
titer results should be interpreted with caution in such cases to avoid providing
a false sense of security. An immunocompetent person is considered fully immunized
2 weeks following administration of the second dose of the 2-dose JYNNEOS vaccination
series, which is when clinical studies have demonstrated maximal antibody titers.
Titer testing might also be considered on a case-by-case basis after vaccination of
persons working with more virulent orthopoxviruses (e.g., Variola virus and Monkeypox
virus).
Minimizing Risk for Occupational Exposures
Many persons with contraindications to vaccination with ACAM2000 (e.g., atopic dermatitis,
immunocompromising conditions, breastfeeding, or pregnancy) may receive vaccination
with JYNNEOS. However, because the number of immunocompromised persons is increasing
in the United States (
14
), and these persons might be less likely to mount an effective vaccine response,
infections in vaccinated persons might occur. Outcomes after an infection in a vaccinated
person could be particularly severe in these populations, particularly following exposure
to more virulent orthopoxviruses (
3
); for this reason, vaccine recipients might consider avoiding high-risk exposures
until after temporary conditions (e.g., pregnancy or transient therapy with immunocompromising
therapeutics) are completed. If high-risk exposures cannot be avoided, persons who
are pregnant, immunocompromised, or breastfeeding or who have atopic dermatitis may
receive JYNNEOS in consultation with their health care provider and after careful
consideration of the risks and benefits. Irrespective of vaccination status, all persons
who work with orthopoxviruses should wear appropriate personal protective equipment.
¶¶¶¶
Future Research
Additional data on JYNNEOS vaccine are needed. Further studies are needed to determine
the duration of protection after the 2-dose JYNNEOS vaccination series; recommendations
regarding the frequency of booster doses can be modified accordingly. The effectiveness
of a single dose JYNNEOS series should be evaluated if orthopoxvirus exposures occur
before peak immunogenicity is achieved. Clinical trials evaluating the risk for myopericarditis
and serious adverse events are needed to ensure that the risks are characterized and
guidance about co-administration of JYNNEOS with mRNA COVID-19 vaccines can be elucidated.
Establishing a correlate of protection after vaccination with JYNNEOS might facilitate
confirmation of effective vaccination in certain populations and might also shed light
on the effectiveness of a single dose of JYNNEOS vaccine. In addition, extensive studies
to date have not identified the specific small mammal reservoir for some orthopoxviruses
(e.g., Monkeypox virus); identifying the specific reservoir might facilitate the identification
of high-risk activities for acquiring orthopoxvirus infections that are not already
recognized.
Summary
What is already known about this topic?
In 2015, the Advisory Committee on Immunization Practices (ACIP) recommended preexposure
prophylaxis with ACAM2000, a replication-competent live virus Vaccinia virus vaccine,
for certain U.S. persons at risk for occupational exposure to orthopoxviruses.
What is added by this report?
In 2019, JYNNEOS, a replication-deficient live Vaccinia virus vaccine was licensed
in the United States. On November 3, 2021, ACIP voted to recommend JYNNEOS preexposure
prophylaxis as an alternative to ACAM2000 for certain persons at risk for exposure
to orthopoxviruses.
What are the implications for public health practice?
A second vaccine is now available for persons for whom vaccination against orthopoxvirus
infections is recommended. Potential vaccinees should weigh the risks and benefits
of each vaccine when deciding which to receive.