To investigate serological correlates of protection against SARS-CoV-2 B.1.617.2 (Delta) infection after two vaccinations.

We performed a case-control study, where cases were Delta infections after the second vaccine dose and controls were vaccinated, never infected participants, matched by age, gender and region. Sera were tested for anti-SARS-CoV-2 Spike antibody levels (anti-S) and neutralising antibody titres (nAbT), using live virus microneutralisation against Ancestral, Delta and Omicron (BA.1, B.1.1.529). We modelled the decay of anti-S and nAbT for both groups, inferring levels at matched calendar times since the second vaccination. We assessed differences in inferred antibody titres between groups and used conditional logistic regression to explore the relationship between titres and odds of infection.

In total, 130 sequence-confirmed Delta cases and 318 controls were included. Anti-S and Ancestral nAbT decayed similarly between groups, but faster in cases for Delta nAbT (p = 0.02) and Omicron nAbT (p = 0.002). At seven days before infection, controls had higher anti-S levels (p < 0.0001) and nAbT (p < 0.0001; all variants) at matched calendar time. A two-fold increase in anti-S levels was associated with a 29% ([95% CI 14–42%]; p = 0.001) reduction in odds of Delta infection. Delta nAbT>40 were associated with reduced odds of Delta infection (89%, [69–96%]; p < 0.0001), with additional benefits for titres >100 (p = 0.009) and >400 (p = 0.007).

We have identified correlates of protection against SARS-CoV-2 Delta, with potential implications for vaccine deployment, development, and public health response.