1. Basic Information
Disease Protected Against
Varicella (Chickenpox) is caused by varicella-zoster virus (VZV). Before vaccination, varicella caused ~4 million cases, ~10,500–13,500 hospitalizations, and ~100–150 deaths annually in the U.S. Complications include bacterial superinfection (primarily Group A Strep), pneumonia, encephalitis, and congenital varicella syndrome. VZV establishes latency in dorsal root ganglia; reactivation later in life causes herpes zoster (shingles).
CDC Schedule (U.S., 2025)
| Dose | Age | Product |
|---|---|---|
| Dose 1 | 12–15 months | Varivax (standalone) or ProQuad (MMRV) |
| Dose 2 | 4–6 years | Varivax or ProQuad. Minimum interval: 3 months between doses. |
Source: CDC ACIP, 2025 schedule. ACIP recommends MMR + varicella separately for dose 1 in children 12–47 months due to MMRV febrile seizure risk; MMRV may be used for dose 2 or for dose 1 in children ≥48 months.
2. Pre-Licensure Clinical Trial Data
Varivax was licensed in 1995 based on clinical trials in ~11,000 children and adults. The pivotal efficacy trial enrolled ~1,000 children. ProQuad (MMRV) was licensed in 2005 based on trials in ~6,000 children.
| Metric | Data |
|---|---|
| Pre-licensure safety database (Varivax) | ~11,000 individuals |
| Efficacy (1 dose) | ~85% (all varicella); ~97% (severe varicella) |
| Efficacy (2 doses) | ~98% (all varicella); near-100% (severe varicella) |
| Most common reactions | Injection site reactions (~20–30%), fever (~10–15%), varicella-like rash (~3–5%, may be infectious) |
MMRV Febrile Seizure Finding
The MMRV pre-licensure trials observed a higher rate of fever (38–40%) and a numerically higher rate of febrile seizures compared to MMR + varicella given separately. The febrile seizure risk was confirmed post-licensure in VSD studies: ~1 additional febrile seizure per 1,250 MMRV doses compared to MMR + varicella given separately, in the 5–12 day post-vaccination window. This led to the ACIP preference for separate MMR + varicella for dose 1.
3. Post-Licensure Safety Data
Varicella vaccine has >30 years of post-licensure safety data. Key VSD findings:
- MMRV febrile seizures: ~1 per 1,250 doses vs. ~1 per 2,500 for MMR + varicella separately (5–12 day window). ACIP preference for separate administration for dose 1 under age 4.
- Herpes zoster (shingles) from vaccine strain: Documented in vaccinated children and adults; rate is lower than after wild-type VZV infection. Estimated at ~18–26 per 100,000 person-years in vaccinated children vs. ~74 per 100,000 after wild-type infection.
- Vaccine-strain transmission: Occasional transmission of vaccine-strain VZV from a vaccinated person who develops a rash to susceptible contacts. Rare; mostly from immunocompromised vaccinees. No documented transmission from vaccinated persons without a rash.
- ITP: MMRV and MMR + varicella both associated with a small ITP risk (attributable primarily to the MMR component — see MMR page).
⚠ Critical Caveat
VAERS data represent unverified reports. A report to VAERS does not mean the vaccine caused the event.
4. Documented Adverse Events
▶ Strong Evidence
- Injection site reactions: 20–30%. Strong
- Fever: 10–15% (Varivax alone); 38–40% (MMRV). Strong
- Varicella-like rash: 3–5% (mild; may be infectious). Strong
- Febrile seizures (MMRV): ~1 per 1,250 doses in the 5–12 day window. Strong
- Herpes zoster (vaccine strain): 18–26 per 100,000 person-years; lower than after wild-type infection. Strong
▶ No Causal Association
- Autism: No association. MMRV contains the same MMR components studied extensively for autism (see MMR page). No Association
5. Disease Prevention Benefits
| Metric | Pre-Vaccine Era (~1990–1994) | Post-Vaccine Era (2-dose, ~2010+) |
|---|---|---|
| Varicella cases (annual) | ~4 million | >97% reduction; varicella is no longer endemic in the U.S. |
| Hospitalizations (annual) | ~10,500–13,500 | >90% reduction; almost exclusively unvaccinated or immunocompromised |
| Deaths (annual) | ~100–150 | <10/year |
| Herpes zoster in children | ~74 per 100,000 | ~18–26 per 100,000 (vaccine-strain); overall pediatric zoster has declined |
Source: CDC Pink Book; MMWR. The introduction of a second dose in 2006 effectively addressed breakthrough varicella observed with the 1-dose schedule. Herd immunity has been observed.
6. Evidence Summary
Varicella vaccine has >30 years of post-licensure data. The safety profile is well-characterized. The primary safety concern is the MMRV-associated febrile seizure risk, which is product-specific and mitigated by ACIP's preference for separate MMR + varicella administration for dose 1. Breakthrough varicella with the 1-dose schedule was addressed by the 2006 2-dose recommendation. Long-term data indicate that vaccine-strain zoster is less common than zoster after wild-type infection.
7. Key References
- IOM. Adverse Effects of Vaccines: Evidence and Causality. National Academies Press; 2012.
- Klein NP, et al. Measles-mumps-rubella-varicella combination vaccine and the risk of febrile seizures. Pediatrics. 2010;126(1):e1–e8.
- CDC. Pink Book — Varicella chapter. cdc.gov/pinkbook
- CDC. VSD. cdc.gov/vaccine-safety/about/vsd.html
- CDC/FDA. VAERS. vaers.hhs.gov