In an immunocompetent individual lacking varicella immunity, how effective is a single dose of live‑attenuated varicella vaccine at preventing clinical infection and severe disease?

Single-Dose Varicella Vaccine Effectiveness in Non-Immune Immunocompetent Individuals

A single dose of varicella vaccine provides approximately 81% protection against all varicella disease and 98% protection against moderate-to-severe disease in immunocompetent individuals without prior immunity, but a two-dose regimen is strongly recommended to achieve optimal protection of 92-98% against all disease. 1, 2

Efficacy of Single-Dose Vaccination

Protection Against All Varicella Disease

• One dose of varicella vaccine demonstrates 81% efficacy (95% CI: 78%-84%) against all forms of varicella disease in meta-analysis of global data 1
• In clinical trials of children receiving single-dose vaccination, breakthrough varicella occurred in only 0.2-3.8% of vaccinees per year over 10 years of follow-up, representing approximately 94% efficacy compared to expected disease rates in unvaccinated individuals 2
• Among adults receiving a single dose, 82% achieved seroconversion to varicella-zoster virus 3

Protection Against Severe Disease

• Single-dose vaccination provides 98% efficacy (95% CI: 97%-99%) against moderate-to-severe varicella 1
• The median VE for prevention of severe disease with one dose was 100% (mean = 99.4%) 1
• When breakthrough varicella occurs after single-dose vaccination, disease is markedly attenuated: 47% of breakthrough cases had <50 lesions compared to only 8% in unvaccinated individuals, and only 7% had >300 lesions compared to 50% in unvaccinated individuals 2

Household Exposure Protection

• Following household exposure to varicella, single-dose vaccination provided 81-90% protection against developing disease 2
• Among vaccinated children exposed in household settings, 84-92% had no breakthrough varicella, while the remaining 8-16% developed only mild disease with a median of <50 lesions 2
• Among adults who received one dose and were subsequently exposed in household settings, 56% were completely protected, and all seven who developed breakthrough illness had modified disease with an average of only 24 vesicles 3

Critical Limitations of Single-Dose Regimen

Suboptimal Immune Response

• Adults demonstrate significantly weaker cell-mediated immunity after single-dose vaccination compared to children (mean stimulation index 9.1 vs. 28.6, p=0.04), explaining the higher breakthrough rate in adults 4
• Approximately 25% of adult vaccinees who initially seroconverted lost detectable antibodies to VZV after single-dose vaccination, though even seronegative individuals retained partial protection 3
• At one year post-vaccination, VZV cell-mediated immunity was significantly lower in adults after one dose compared to children (10.0 vs. 15.6, p=0.02) 4

Age-Specific Seroconversion Rates

• In adults receiving a single dose, only 82% achieved seroconversion, leaving 18% without detectable antibody response 3
• A second dose increases adult seroconversion rates to 94%, addressing the initial vaccine failure in nearly two-thirds of non-responders 3

Two-Dose Regimen: The Evidence-Based Standard

Superior Efficacy

• Two doses provide 92-98% protection against all varicella disease, representing a 3.4-fold lower risk of breakthrough varicella compared to single-dose vaccination (2.2% vs. 7.5% over 10 years, p<0.001) 2, 1
• The second dose adds 11 percentage points of additional protection against all varicella (from 81% to 92%) 1
• Immune responses after two doses are significantly higher and approximate levels seen after natural disease 5

Guideline-Mandated Dosing Schedule

• All immunocompetent adults ≥13 years without evidence of immunity must receive two 0.5-mL doses of single-antigen varicella vaccine administered subcutaneously, separated by 4-8 weeks (minimum interval: 4 weeks) 6, 7
• For children aged 12 months to 12 years, the two doses should be separated by ≥3 months 6
• The minimum acceptable interval is 4 weeks for adults, though extending to 8 weeks may yield higher antibody titers 7

Common Pitfalls and Clinical Caveats

Do Not Rely on Single-Dose Protection

• While single-dose vaccination provides substantial protection against severe disease, relying on one dose leaves patients with suboptimal immunity and 3.4-fold higher breakthrough risk 2
• The second dose is not merely a "booster" but addresses primary vaccine failure in 12-18% of initial recipients 3, 5

Antibody Testing Limitations

• Commercial ELISA assays lack sufficient sensitivity to detect vaccine-induced immunity, which produces lower antibody levels than natural infection 8
• Do not repeat vaccination based solely on negative commercial antibody titers after completing the two-dose series; documented receipt of two properly-spaced doses supersedes serologic results 8

Special Population Considerations

• Pregnancy is an absolute contraindication to varicella vaccination; the vaccine should be administered postpartum before hospital discharge 7
• Severe immunocompromising conditions (HIV with CD4 <200 cells/µL, active malignancy, high-dose immunosuppressive therapy) are contraindications to live-attenuated varicella vaccine 6, 9, 7
• For immunocompromised patients requiring vaccination, it must be administered ≥4 weeks before initiating highly immunosuppressive therapy, and only single-antigen varicella vaccine (not MMRV) should be used 6, 9