A 28-year-old healthcare worker in Delhi undergoes post-exposure prophylaxis (PEP) after a needlestick injury from an HBV-positive patient. At 6 weeks post-exposure, serology shows: HBsAg (−), anti-HBs (+), anti-HBc (−). Which serological pattern best distinguishes successful vaccination response from resolved natural HBV infection?

## Distinguishing Vaccine Response from Natural Infection Recovery ### The Critical Discriminator: Anti-HBc Status **Key Point:** The presence or absence of anti-HBc (total anti-HBc, which includes both IgM and IgG) is the single best marker that distinguishes **vaccine-induced immunity** from **naturally acquired immunity** (resolved infection). - **Vaccinated individuals:** Anti-HBs (+), anti-HBc (−) - **Naturally infected (resolved):** Anti-HBs (+), anti-HBc (+) ### Comparative Serology Table | Serological Pattern | HBsAg | Anti-HBs | Anti-HBc | Interpretation | |---------------------|-------|----------|----------|----------------| | **Vaccine response** | − | + | **−** | Immune from vaccination | | **Resolved infection** | − | + | **+** | Immune from natural infection | | Acute infection | + | − | + (IgM) | Active acute HBV | | Chronic infection | + | − | + (IgG) | Active chronic HBV | | Susceptible | − | − | − | No immunity | ### Clinical Pearl **High-Yield:** In this healthcare worker, the pattern HBsAg (−), anti-HBs (+), anti-HBc (−) indicates **successful vaccine response**. The absence of anti-HBc proves that the patient never had natural HBV infection; the anti-HBs is purely from vaccination (HEPLISAV-B or other HBV vaccine given as PEP). ### Why Anti-HBc is the Perfect Discriminator 1. **Anti-HBc appears only after natural infection:** It is produced by B cells in response to the HBc (core) antigen, which is only present during actual viral replication 2. **Anti-HBc does NOT appear after vaccination:** Vaccines contain only HBsAg (surface antigen), not HBc; therefore vaccinated individuals never develop anti-HBc 3. **Anti-HBc persists for life:** Once acquired through natural infection, it remains detectable indefinitely, even if anti-HBs wanes **Mnemonic:** **"Core = Natural; Surface = Vaccine"** — Anti-HBc (core antibody) = proof of natural infection; anti-HBs alone (surface antibody) = proof of vaccination. ### Why Other Patterns Fail as Discriminators - **Anti-HBs alone (without anti-HBc):** This is the vaccine response pattern — correct answer - **Anti-HBc IgG with anti-HBs:** This indicates resolved natural infection, not vaccination - **HBsAg with anti-HBs:** This is rare and suggests either acute-on-chronic infection or a false-positive; not a discriminatory pattern for vaccine vs. natural immunity