Zoster Antibody Testing Does Not Reliably Predict Prior Vaccination Status
Varicella-zoster virus (VZV) IgG antibody testing should not be used to determine whether someone has received a shingles vaccine, as antibody levels do not correlate with vaccination history and commercial assays were not designed to detect vaccine-induced immunity.
Why Antibody Testing Fails to Predict Vaccination
Fundamental Immunologic Mismatch
Protection against herpes zoster is primarily conferred by cell-mediated immunity, not antibody levels, making serologic testing an inappropriate marker for vaccine-induced protection 1, 2, 3.
Herpes zoster arises from reactivation of latent VZV due to declining cell-mediated immunity, not from low antibody titers; therefore, antibody levels do not reliably predict zoster risk or vaccine status 4.
The recombinant zoster vaccine (Shingrix/RZV) restores both cellular and humoral immunity via its AS01B adjuvant, achieving >90% efficacy across all age groups independent of baseline antibody levels 4, 5.
Commercial Assay Limitations
Commercial VZV ELISA assays were designed to measure the higher titers associated with natural infection rather than the lower titers induced by vaccination 6.
Available commercial tests for VZV IgG have suboptimal sensitivity and are not optimized to detect antibody to the vaccine virus 7.
Even after multiple doses of varicella vaccine, some individuals demonstrate persistent serologic non-responsiveness on standard ELISA testing despite having adequate cell-mediated immunity and clinical protection 6.
Vaccine-Specific Antibody Patterns
While RZV recipients maintain higher anti-glycoprotein E (anti-gE) antibody levels and avidity for 5 years compared to Zostavax (ZVL) recipients, these measurements reflect vaccine immunogenicity rather than serving as markers of prior vaccination 1.
Anti-gp antibody levels decrease to prevaccination levels or below beyond 1 year after vaccination in both RZV and ZVL recipients, making retrospective detection of vaccination unreliable 1.
The antibody response to VZV vaccine may be low in a subgroup of individuals despite an adequate cell-mediated response, and repeated immunizations plus more sensitive measures of VZV-specific IgG would be needed to validate protection 6.
Guideline-Based Approach: Skip Antibody Testing Entirely
For Immunocompetent Adults ≥50 Years
The CDC, Canadian, and German guideline societies issue a strong recommendation that varicella-history review or laboratory testing should not be performed before administering herpes-zoster vaccination to adults ≥50 years 4.
Adults ≥50 years should receive the recombinant zoster vaccine (RZV/Shingrix) in a 2-dose series given 2-6 months apart, without any prior serologic testing 4.
No safety concerns have been identified when giving either the recombinant or live-attenuated zoster vaccines to individuals who are actually VZV-seronegative, supporting vaccination without titer screening 4.
Vaccination should not be delayed to obtain antibody titers, as this contradicts guideline recommendations and leaves patients unnecessarily exposed to herpes zoster 4.
For Immunocompromised Adults
CDC guidance advises clinicians to consider age, documented prior varicella (or vaccination), and serology when deciding on RZV for immunocompromised adults, with the primary decision being whether the patient needs varicella vaccine (if truly seronegative) or zoster vaccine (if seropositive) 4.
For immunocompromised adults under 50 years, a documented varicella-vaccination history and serologic testing should be evaluated before giving RZV 4.
In most immunocompromised adults ≥18 years, RZV should be administered regardless of varicella history, using a shortened schedule of doses 1-2 months apart 4.
Critical Clinical Pitfalls
Do Not Use Antibody Testing to Decide on Revaccination
Adults who previously received Zostavax should receive the full 2-dose Shingrix series regardless of antibody levels, as Zostavax efficacy wanes to only 14.1% by year 10 7, 4.
Vaccination is recommended after a previous zoster episode regardless of presumed antibody status, because natural infection does not provide reliable protection against recurrence (10-year cumulative recurrence risk is 10.3%) 4, 8.
Seroprevalence Data Supports Empiric Vaccination
Population studies show 88-91% of adults have VZV exposure despite lacking a recalled chickenpox episode, making routine serologic testing unnecessary and cost-ineffective 4.
Among healthcare workers, seropositivity rates range from 72% to 88% 4.
Routine serologic screening would identify very few truly seronegative individuals, adds unnecessary cost, and delays protective vaccination 4.
The Only Exception: Confirming VZV Seropositivity in Select Cases
If a patient is documented VZV-seronegative, the recommended approach is a 2-dose varicella vaccine series spaced 4 weeks apart, rather than a zoster vaccine 4.
At diagnosis of IBD or before starting immunosuppressive therapy, unvaccinated adults and children should be screened by history of chickenpox (or shingles) for susceptibility to primary infection, and if the history is uncertain or negative, or the patient grew up in a tropical or subtropical climate, they should be tested for varicella zoster virus IgG 7.
It is important to avoid testing a sample which may contain VZV IgG obtained passively, for example by blood transfusion 7.