# Circulating neutralizing antibodies and SARS-CoV-2 variant replication following postvaccination infections

## TL;DR

Higher pre-infection antibodies reduce SARS-CoV-2 replication in vaccinated individuals, but Omicron variants escape this effect.

## Contribution

Quantified the effect of baseline neutralizing antibodies on viral shedding in postvaccination infections with different SARS-CoV-2 variants.

## Key findings

- Baseline neutralizing antibodies correlate with reduced viral load and shorter shedding in Delta infections.
- Omicron infections show no correlation between baseline antibodies and viral outcomes.
- Ancestral boosters induce broader and higher neutralizing antibody responses compared to primary vaccination.

## Abstract

The effect of preexisting neutralizing antibodies (NAb) on SARS-CoV-2 shedding in postvaccination infection (PVI) is not well understood. We characterized viral shedding longitudinally in nasal specimens in relation to baseline (pre/periinfection) serum NAb titers in 125 participants infected with SARS-CoV-2 variants. Among 68 vaccinated participants, we quantified the effect of baseline NAb titers on maximum viral RNA titers and infectivity duration. Baseline NAbs were higher and targeted a broader range of variants in participants with monovalent ancestral booster vaccinations compared with those with a primary vaccine series. In Delta infections, baseline NAb titers targeting Delta or Wuhan-Hu-1 correlated negatively with maximum viral RNA. Per log10 increase in Delta-targeting baseline NAb IC50, maximum viral load was reduced –2.43 (95% CI: –3.76, –1.11) log10 nucleocapsid copies, and infectious viral shedding was reduced –2.79 (95% CI: –4.99, –0.60) days. Conversely, in Omicron infections (BA.1, BA.2, BA.4, or BA.5), baseline NAb titers against Omicron lineages or Wuhan-Hu-1 did not predict viral outcomes. Our results provide robust estimates of the effect of baseline NAbs on the magnitude and duration of nasal viral replication after PVI (albeit with an unclear effect on transmission) and show how immune escape variants efficiently evade these modulating effects.

Higher neutralizing antibody titres against SARS-CoV-2 before an infection limits virus replication and infection duration, however escape variants evade this effect.