Smallpox

Laboratory personnel working with orthopoxviruses (variola, vaccinia, monkeypox). Military personnel (US DoD ongoing program). Biodefense stockpile preparedness personnel. Designated emergency response teams (Strategic National Stockpile). Healthcare workers designated for smallpox response. Jynneos: also indicated for mpox prevention (see separate Mpox Vaccine entry). NOT indicated for general public — smallpox is eradicated.

ACAM2000: severe eczema/atopic dermatitis (risk of eczema vaccinatum), immunocompromised persons (risk of progressive vaccinia), pregnancy (risk of fetal vaccinia), cardiac disease (myocarditis risk), household contacts with above conditions, breastfeeding, age <1 year. Jynneos: severe allergic reaction to previous dose or component; pregnancy (use only if benefit outweighs risk). ACAM2000 has significantly more contraindications than Jynneos.

ACAM2000: expected vaccination site reaction (papule → vesicle → pustule → scab over 2–3 weeks). Inadvertent inoculation to other body sites (face, genitals — 6/10,000). Generalized vaccinia (3/10,000). Myopericarditis (5.7/1,000, usually mild). Eczema vaccinatum (in eczema patients): severe, potentially fatal. Progressive vaccinia (vaccinia necrosum): in immunocompromised — potentially fatal. Jynneos: injection site pain (85%), redness, swelling, fatigue (30%), headache (18%). No myocarditis signal. No risk of progressive vaccinia (non-replicating).

ACAM2000: single dose via scarification (bifurcated needle, 15 punctures with vaccinia-containing droplet). Major reaction ("take") expected — vesicle/pustule at site. Check vaccination take at 6–8 days. Jynneos: 2 doses of 0.5 mL SC (not IM), 28 days apart. Previously smallpox-vaccinated: single Jynneos booster. ACAM2000 booster: every 3 years for ongoing risk (laboratory workers).

ACAM2000: historically ~95% effective against smallpox (pre-eradication data). Cross-protection against mpox: ~85%. Vaccination within 3 days of smallpox exposure prevents disease in most cases. Jynneos: see Mpox Vaccine entry for mpox effectiveness data. Orthopoxvirus cross-neutralizing antibodies: detectable in >95% after Jynneos 2-dose series.

ACAM2000: frozen at -15°C to -25°C. Reconstituted: use within 18 hours. Jynneos: frozen at -20°C (long-term) or +2°C to +8°C for up to 8 weeks.

ACAM2000: do not co-administer with live vaccines (including varicella, MMR) — risk of dissemination. Jynneos: standard live vaccine spacing (same day or ≥28 days for other live vaccines; any interval for inactivated vaccines). VIG (vaccinia immune globulin) is used to treat ACAM2000 complications — does not interfere with vaccination.

Pregnancy: ACAM2000 contraindicated (fetal vaccinia documented). Jynneos: limited data; use only in emergency when benefit outweighs risk. Breastfeeding: ACAM2000 contraindicated (live vaccinia in lesion). Jynneos: expected safe (non-replicating).

ACAM2000: not for <1 year. Jynneos: approved ≥18 years (US), ≥1 year (EU — as Imvanex). Pediatric ACAM2000 use only in emergency.

ACAM2000: vaccination site is INFECTIOUS until scab separates. Strict wound care: keep covered, wash hands, avoid contact with immunocompromised/eczema/pregnant individuals. Healthcare workers: may need reassignment during vaccination take. Jynneos: no wound care needed (no skin lesion). Both vaccines cross-protect against variola, vaccinia, and mpox. Pre-event vaccination (ACAM2000): use only in designated personnel — adverse events exceed benefit in general population.