Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for Preexposure Vaccination of Persons at Risk for Occupational Exposure to Orthopoxviruses

Recommendations of the Advisory Committee on Immunization Practices -- United States, 2022

Agam K. Rao, MD; Brett W. Petersen, MD; Florence Whitehill, DVM; Jafar H. Razeq, PhD; Stuart N. Isaacs, MD; Michael J. Merchlinsky, PhD; Doug Campos-Outcalt, MD; Rebecca L. Morgan, PhD; Inger Damon, MD, PhD; Pablo J. Sánchez, MD; Beth P. Bell, MD

Disclosures

Morbidity and Mortality Weekly Report. 2022;71(22):734-742.

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.

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Abstract and Introduction
Methods
Summary of Findings and Rationale for Recommendations
Recommendations
Clinical Guidance
Future Research
References
Sidebar

^§§Research laboratory personnel are those who directly handle cultures or animals contaminated or infected with replication-competent vaccinia virus, recombinant vaccinia viruses derived from replication-competent vaccinia strains (i.e., those that are capable of causing clinical infection and producing infectious virus in humans), or other orthopoxviruses that infect humans (e.g., Monkeypox virus, Cowpox virus, and Variola virus).
^¶¶Clinical laboratory personnel who perform routine chemistry, hematology, and urinalysis testing, including for patients with suspected or confirmed orthopoxvirus infections, are not included in this recommendation because their risk for exposure is very low.
***Public health authorities, at their own discretion, may approve a cohort of health care personnel, public health personnel, or both, to receive primary vaccination against orthopoxviruses for preparedness purposes (e.g., first responders who might participate in a smallpox or monkeypox outbreak).
^††† https://www.fda.gov/media/75792/download
^§§§For example, those caring for patients enrolled in clinical trials for replication-competent orthopoxvirus vaccines and those caring for persons with suspected or confirmed orthopoxvirus infections (e.g., clinicians and environmental services personnel).
^¶¶¶Continued risk refers to persistent risk due to occupational work performed. Designated public health and healthcare worker response teams approved by public health authorities are not at "continued risk" because they are vaccinated for the purposes of preparedness.

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
Recommendations	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.

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
Characteristic	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

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	Household contact with condition*
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.