Orthopoxvirus Vaccines
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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.
No material clinical or coverage changes in this revision.
Coverage and Medical Necessity Criteria
Covered Indications (smallpox and monkeypox)
Aetna considers orthopoxvirus vaccines medically necessary for the following indications when criteria are met:
Re-vaccination may be medically necessary as frequently as every 3 years.
Most clinicians and laboratorians not performing orthopoxvirus diagnostic testing are not advised to receive PrEP.
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
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):
CDC supply considerations may alter need/timing of the second dose in persons with prior infection or when supply is limited.
ACAM2000 is available for monkeypox under Expanded Access IND; contraindications and potential adverse events should be considered.
JYNNEOS may be preferred for immunocompromised or eczema patients due to a more favorable safety profile compared with ACAM2000.
Covered Indications (PEP, PEP++, PrEP)
Coverage aligned with CDC recommendations for vaccination in the context of exposure risk and occupational risk
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 selection and prioritization
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
| 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. |
| 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 listed |
Provider Requirements, Prior Authorization, and Administration Guidance
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
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.
- 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
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
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
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
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
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
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
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
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