CurrentAetnaPolicy 0644

Orthopoxvirus Vaccines

Medical necessity and coverage policy for orthopoxvirus vaccines (smallpox and monkeypox/JYNNEOS/ACAM2000) including pre- and post-exposure use as advised by public health authorities; affects clinicians, laboratorians, designated public health and response personnel, and insured members under Aetna plans.

Policy Summary

PayerAetna

PolicyOrthopoxvirus Vaccines

Policy CodePolicy 0644

Change TypeNo material change

Effective DateSep 17, 2002

Next Review DateJul 11, 2024

Key ActionUse JYNNEOS or ACAM2000 when Aetna medical necessity criteria are met and follow CDC/EUA guidance for product selection, dosing, and documentation.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

2primary vaccine products discussed (JYNNEOS, ACAM2000)

4 daysPEP recommended timing (best chance to prevent disease)

1 in 175approx myocarditis/pericarditis rate after ACAM2000

0.5 / 0.1 mLJYNNEOS subc / intradermal dosing

>=3 yearsre-vaccination interval referenced

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Coverage and Medical Necessity Criteria

Covered Indications (smallpox and monkeypox)

Aetna considers orthopoxvirus vaccines medically necessary for the following indications when criteria are met:

Smallpox pre-exposure (PrEP): Pre-exposure immunization with orthopoxvirus (smallpox) vaccine when public health authorities advise; ACIP recommends for laboratory workers handling non-highly attenuated smallpox virus/materials, persons pre-designated to investigate/follow-up initial smallpox cases with direct patient contact, and selected personnel in pre-designated referral facilities.

Re-vaccination may be medically necessary as frequently as every 3 years.

Smallpox post-exposure: Orthopoxvirus (smallpox) vaccine for persons who have or may have been exposed to smallpox or other non-highly attenuated vaccinia virus; ACIP recommends post-exposure vaccination for persons with recent exposure.

Monkeypox pre-exposure (PrEP): PrEP monkeypox vaccination when public health authorities advise; ACIP recommends for clinical laboratory personnel who perform orthopoxvirus testing, research lab workers who handle cultures/animals contaminated with orthopoxviruses, and certain healthcare/public health response team members designated by authorities.

Most clinicians and laboratorians not performing orthopoxvirus diagnostic testing are not advised to receive PrEP.

Monkeypox post-exposure (PEP/PEP++): PEP or expanded PEP (known or presumed exposure) when public health authorities advise; ACIP recommends for identified contacts, people with a recent sex partner diagnosed with monkeypox, and certain MSM/transgender people with recent high-risk sexual exposures.14 days (recent sexual partner or exposures window)

Prioritize JYNNEOS doses for people at high risk for severe disease or adverse events from ACAM2000 (e.g., immunocompromised, pregnant).

Product selection and regulatory notes

Vaccine selection and EUA considerations: Either JYNNEOS (MVA) or ACAM2000 can be used for PEP, PEP++, or PrEP after risk-benefit discussions and review of conditions that could increase risk for serious adverse events; FDA has issued EUAs for certain uses of JYNNEOS (pediatric subcutaneous use and intradermal adult administration) which require adherence to EUA conditions.

Potential pediatric use and intradermal adult administration of JYNNEOS require consultation with CDC and following EUA/fact sheet conditions.

Vaccine indications and administration considerations

Coverage considerations described in document background (clinical indications, product-specific notes, and CDC supply-based exceptions):

JYNNEOS approval/administration: JYNNEOS is FDA-approved for prevention of smallpox and monkeypox in adults 18+ at high risk; standard schedule is two 0.5 mL subcutaneous doses 4 weeks apart with maximal immune response 14 days after the second dose; an EUA permits intradermal administration in adults and subcutaneous use in certain pediatric high-risk individuals.

CDC supply considerations may alter need/timing of the second dose in persons with prior infection or when supply is limited.

ACAM2000 approval/administration: ACAM2000 is FDA-approved for smallpox immunization in persons at high risk; it contains replication-competent vaccinia and is administered once via percutaneous scarification (15 punctures delivering 0.0025 mL); immune response is maximal around 4 weeks.

ACAM2000 is available for monkeypox under Expanded Access IND; contraindications and potential adverse events should be considered.

Clinical groups at higher risk for severe mpox: Persons with weakened immune systems, young children, people with eczema, and pregnant or breastfeeding people may be at increased risk for severe disease and warrant consideration for vaccination per public health guidance.

Covered Indications (PEP, PEP++, PrEP)

Coverage aligned with CDC recommendations for vaccination in the context of exposure risk and occupational risk

Covered indications: Vaccination (JYNNEOS or ACAM2000) for post-exposure prophylaxis (PEP) of known contacts identified by public health; expanded PEP (PEP++) for known or presumed exposures including a recent sex partner within 14 days or certain high-risk sexual behaviors; pre-exposure prophylaxis (PrEP) for persons in specified occupational risk groups (e.g., laboratory personnel, designated response teams).

Follow CDC timing: ideally within 4 days of exposure for best chance to prevent disease; vaccination 4–14 days after exposure may reduce severity.

Vaccine selection and prioritization

Vaccine choice logic: Either JYNNEOS or ACAM2000 may be used for PEP, PEP++, or PrEP after a risk-benefit discussion; ACIP recommends JYNNEOS as an alternative to ACAM2000 for primary vaccination of laboratory and designated response personnel, and JYNNEOS doses should be prioritized for people at high risk for severe disease or at increased risk of serious adverse events from ACAM2000 when supply is limited.

Consider contraindications to ACAM2000 (e.g., immunocompromise, eczema, pregnancy, cardiac disease) when selecting vaccine.

The ACIP does not recommend routine smallpox vaccination of the general population because the risk of vaccine-related complications outweighs the currently low risk of smallpox from intentional release. As a result, vaccination of the general public is not advised and most benefit plans exclude coverage for vaccines given solely for work or travel requirements; providers should verify individual plan benefit descriptions for coverage exceptions.

Historically, live-attenuated vaccines have been considered contraindicated during pregnancy due to uncertain safety for the mother–infant dyad. Systematic review data cited in the policy found higher odds of malformations and miscarriage after first‑trimester smallpox vaccination in some analyses, so pregnancy status should be considered when deciding timing and choice of vaccine and consultation with public health or CDC is appropriate for nonstandard uses.

Certain populations should not receive ACAM2000 because of increased risk for serious adverse events. These include individuals with severely weakened immune systems, infants under 12 months, people with congenital or acquired immunodeficiency (including those on immunosuppressive medications and people living with HIV), persons with eczema or other exfoliative skin conditions, pregnant persons, those with cardiac disease, and patients with certain eye conditions treated with topical steroids.

The CDC does not recommend widespread routine monkeypox (mpox) vaccination at this time. PrEP and PEP recommendations are targeted to specific occupational groups, known contacts, and persons with epidemiologic risk factors; most clinicians and laboratorians who are not performing orthopoxvirus testing are not advised to receive pre‑exposure vaccination.

Not explicitly stated in this portion of the policy.

Billing and Coding

Covered CPT CodesCPTCovered

90611	Smallpox and monkeypox vaccine, attenuated vaccinia virus, live, non-replicating, preservative free, 0.5 mL dosage, suspension, for subcutaneous use.
90622	Vaccinia (smallpox) virus vaccine, live, lyophilized, 0.3 mL dosage, for percutaneous use.

Other related CPT CodesCPT

86580	Skin test; tuberculosis, intradermal.
87593	Infectious agent detection by nucleic acid (DNA or RNA); orthopoxvirus (eg, monkeypox virus, cowpox virus, vaccinia virus), amplified probe technique, each.
90460	Immunization administration through 18 years of age via any route of administration, with counseling by physician or other qualified health care professional; first or only component of each vaccine or toxoid administered.
90461	Each additional vaccine or toxoid component administered (List separately in addition to code for primary procedure).
90471	Immunization administration (includes percutaneous, intradermal, subcutaneous, or intramuscular injections); 1 vaccine (single or combination vaccine/toxoid).
90472	Each additional vaccine (single or combination vaccine/toxoid) (List separately in addition to code for primary procedure).
90749	Unlisted vaccine/toxoid.

Covered ICD-10 CodesICD-10Covered

Z20.2	Contact with and (suspected) exposure to infections with a predominantly sexual mode of transmission.
Z20.89	Contact with and (suspected) exposure to other communicable diseases [smallpox].
Z23	Encounter for immunization [pre-exposure to smallpox - see criteria].
Z72.51	High risk heterosexual behavior.
Z72.52	High risk homosexual behavior.
Z72.53	High risk bisexual behavior.

No codes in this document portionmixed

No codes listed

Provider Requirements, Prior Authorization, and Administration Guidance

Prior Authorization

Prior authorization / coverage conditioned on criteria

Vaccines are covered when Aetna medical necessity criteria and applicable public health recommendations are met. Verify member benefit plan descriptions for exclusions (many plans exclude coverage of vaccinations required for work or travel).

Check member benefit plan for exclusions for work- or travel-related vaccinations
Coverage conditioned on meeting Aetna selection/medical-necessity criteria and public health guidance

Note

Vaccine eligibility and dosing considerations

Follow CDC and FDA guidance for vaccine eligibility, dosing, and route. JYNNEOS is a 2-dose (0.5 mL) subcutaneous series 4 weeks apart for adults; when supply-constrained, CDC has provided modified recommendations including consideration of delaying or omitting the second dose in certain situations and authorizing intradermal 0.1 mL dosing for adults under an EUA. ACAM2000 is single-dose percutaneous scarification and is replication-competent; product selection should consider differences in replication competence, contraindications, and risk-benefit for the individual.

Clinical and Epidemiological Background

Smallpox (variola) primarily transmits after rash onset and by large respiratory droplets; control relies on public health measures including active surveillance, case isolation, contact tracing, and targeted "ring" vaccination of contacts and at‑risk personnel. Vaccines available from the Strategic National Stockpile (notably JYNNEOS and ACAM2000) are used in these containment strategies, with timing of post‑exposure vaccination guided by CDC (ideally within 4 days of exposure to prevent disease and up to 14 days to reduce severity).

Key Terms and Vaccine Descriptions

inv-32: JYNNEOS — 2-dose non-replicating MVA vaccine; administration options and EUA context

ProductJYNNEOS (MVA) — a 2-dose, non-replicating modified vaccinia Ankara vaccine (Imvamune/Imvanex).

FDA / EUA contextFDA-approved for prevention of smallpox and monkeypox in adults at high risk; Emergency Use Authorization (EUA) permits intradermal administration (0.1 mL) in adults and subcutaneous use in certain individuals <18 years during the public health emergency.

Standard dosing and routeTwo 0.5 mL subcutaneous injections given 4 weeks apart; maximal immune response ~14 days after the second dose.

EUA alternative regimenIn the 2022 PHE, an intradermal 0.1 mL alternative regimen for adults is authorized under EUA — providers must follow EUA/fact sheet when using intradermal route.

Supply and prioritization noteCDC guidance includes supply-based considerations that may alter timing or need for the second dose and prioritization of JYNNEOS for people at high risk for severe disease or adverse events from ACAM2000.

Policy Summary

PayerAetna

PolicyOrthopoxvirus Vaccines

Policy CodePolicy 0644

Change TypeNo material change

Effective DateSep 17, 2002

Next Review DateJul 11, 2024

Key ActionUse JYNNEOS or ACAM2000 when Aetna medical necessity criteria are met and follow CDC/EUA guidance for product selection, dosing, and documentation.

SourceLink

On This Page

JYNNEOS may be preferred for immunocompromised or eczema patients due to a more favorable safety profile compared with ACAM2000.

JYNNEOS standard: 2 doses, 0.5 mL subcutaneous, 4 weeks apart; maximal immune response ~14 days after second dose
Under FDA EUA (Aug 9, 2022): intradermal 0.1 mL dosing for adults ≥18 and subcutaneous for <18 when indicated
CDC supply-limited guidance: may defer second dose for persons with prior infection or in certain circumstances; immunocompromised persons considered case-by-case
ACAM2000: single percutaneous dose (0.0025 mL via multiple puncture scarification); replication-competent with different contraindications and adverse-event profile

Prior Authorization

Prior authorization

No specific Aetna prior authorization form or requirement is specified in these excerpts; however, providers should verify prior authorization requirements per member plan and document clinical indication, exposure status, and medical necessity when submitting claims.

Confirm whether prior authorization is required by the member's benefit plan before vaccination
Document exposure status, timing, route, and volume administered when applicable

Denial Risk

Most plans exclude coverage of vaccinations required for work or travel

Most plans exclude coverage of vaccinations required for employment or travel. Always check the member's benefit plan description and document exceptions if coverage is authorized.

If vaccination is for work or travel, expect exclusion unless the member's plan specifically provides coverage
Obtain prior authorization or payment arrangements when coverage is excluded

Documentation Required

EUA requirements for intradermal JYNNEOS

When using intradermal administration of JYNNEOS under the EUA, follow the FDA EUA and associated fact sheet for healthcare providers and recipients, including authorized dosing, administration technique, and documentation requirements.

Use intradermal 0.1 mL dosing only per FDA EUA and document EUA use on the encounter
Provide and retain EUA fact sheet acknowledgements as required

Note

Links to non-Aetna sites are provided for convenience

Links to non-Aetna sites (CDC, FDA, manufacturer guidance, and others) are provided for convenience; Aetna is not responsible for content or privacy practices of those sites. Use referenced public health guidance when making clinical decisions and when documenting medical necessity.

Refer to CDC and FDA guidance for up-to-date clinical recommendations and EUA details
Aetna links list provided in Additional Information; validate external content at source

Documentation Required

PCR testing of lesion swabs recommended for diagnosis

For suspected monkeypox cases, perform PCR testing of lesion swabs per CDC guidance and document epidemiologic risk factors and lesion characteristics in the medical record to support diagnosis and any subsequent vaccination decisions.

Obtain lesion swab for orthopoxvirus PCR (LRN or qualified commercial lab)
Document lesion characteristics, exposure history, and public health notifications as applicable

Note

Two different FDA-approved vaccines (replicating and non-replicating) — selection considerations

Two FDA-authorized/approved vaccines are relevant: JYNNEOS (non-replicating, two-dose primary series for standard subcutaneous use; EUA allows intradermal for adults) and ACAM2000 (replication-competent, single percutaneous dose). Selection should consider product-specific differences, contraindications (e.g., immunocompromise, pregnancy), supply, and CDC prioritization guidance.

JYNNEOS: live, non-replicating vaccine; standard 2-dose 0.5 mL subcutaneous series
ACAM2000: live, replication-competent vaccine given by scarification; different contraindications and adverse-event profile
CDC recommends prioritizing JYNNEOS for many groups and for certain occupational exposure settings

inv-33: ACAM2000 — live, replication-competent vaccinia vaccine administered via percutaneous scarification; special handling/administration notes

ProductACAM2000 — a live, replication-competent vaccinia virus vaccine for smallpox (contains live vaccinia).

FDA approval and expanded accessFDA-approved for active immunization against smallpox; made available for monkeypox under an Expanded Access IND during the outbreak.

Administration methodAdministered once via percutaneous scarification (multiple puncture technique using a bifurcated needle).

Dose volume and techniqueA droplet of 0.0025 mL of reconstituted vaccine is applied and delivered by 15 jabs of a bifurcated needle (scarification).

Provider training and restrictionsMust be administered only by providers trained to safely and effectively perform percutaneous scarification; not to be given by intradermal, subcutaneous, intramuscular, or intravenous routes.

inv-34: JYNNEOS (alternate inventory entry) — replication-deficient MVA vaccine FDA-approved for adults at high risk

ProductJYNNEOS (replication-deficient MVA) — FDA-approved for prevention of smallpox and monkeypox in adults 18+ at high risk (also known as Imvamune/Imvanex).

Standard scheduleTwo 0.5 mL subcutaneous injections 4 weeks apart; immune response maximal ~14 days after second dose.

EUA-authorized usesEUA allows intradermal administration (0.1 mL) for adults and subcutaneous use for certain individuals <18 years during the emergency; these uses are not standard FDA approvals and require adherence to EUA conditions.

Comparative effectiveness noteClinical studies show comparable immune response to ACAM2000, but limited real-world effectiveness data exist for the 2022 outbreak; second dose needed to reach comparable antibody response in trials.

inv-35: ACAM2000 (alternate inventory entry) — replication-competent vaccine FDA-approved for smallpox and available under expanded access for monkeypox

ProductACAM2000 — replication-competent live vaccinia vaccine FDA-approved for smallpox and available under Expanded Access IND for monkeypox use during outbreaks.

Dose and immune responseSingle percutaneous dose (0.0025 mL droplet) delivered by multiple puncture; immune response peaks around 4 weeks; successful inoculation produces a local 'take' (pustule) that may take ~6+ weeks to heal.

Administration constraintsRequires trained providers for percutaneous scarification; manufacturer ensures training availability per its Risk Management Plan.

Safety/selection considerationsReplication-competent nature and safety profile mean ACAM2000 may be less preferred for immunocompromised people, pregnant persons, or those with eczema — consider JYNNEOS when appropriate.

inv-36: Probable vs Confirmed case (mpox) definitions

Probable case (mpox)Detection of Orthopoxvirus DNA by PCR from a clinical specimen or anti-orthopoxvirus IgM (4–56 days after rash onset) without suspicion of other recent orthopoxvirus exposure (e.g., recent vaccinia from vaccination).

Confirmed case (mpox)Demonstration of monkeypox virus DNA by PCR or next-generation sequencing from a clinical specimen, or isolation of monkeypox virus in culture.

Diagnostic specimen guidancePCR testing should be performed on lesion swab samples; testing of non-lesion samples (blood, saliva) is not supported and may yield false results.

inv-37: Definitions for PEP / PEP++ / PrEP

PEP (post-exposure prophylaxis)Vaccination of known contacts identified by public health to prevent disease after a documented exposure; ideally given within 4 days of exposure to prevent disease (4–14 days may reduce severity).

PEP++ (expanded post-exposure)Vaccination for known or presumed exposures such as recent sex partner diagnosis or certain high-risk sexual behaviors within the past 14 days — used when public health advises expanded post-exposure vaccination.

PrEP (pre-exposure prophylaxis)Pre-exposure vaccination for persons in specified occupational risk groups (e.g., laboratorians performing orthopoxvirus testing, designated response personnel) when public health authorities advise. Prioritize JYNNEOS for those at higher risk of severe disease or adverse events from ACAM2000.

inv-38: Scarification (percutaneous) definition and administration detail for ACAM2000

DefinitionScarification (percutaneous multiple puncture) — method of ACAM2000 administration using a bifurcated needle to deliver 15 jabs.

Dose deliveredA droplet of 0.0025 mL of reconstituted vaccine is picked up on the bifurcated needle and applied via 15 punctures to the skin; this is the intended percutaneous dose.

Route restrictionsACAM2000 must not be given by intradermal, subcutaneous, intramuscular, or intravenous routes; it must be given only by the percutaneous scarification technique by trained providers.

Expected local reactionA successful inoculation typically produces a pustule or 'take' at the site that indicates a protective immune response and may take up to ~6 weeks or more to heal.