# Impact of First SARS‐CoV‐2 Infection Variant on Serological Responses Against Omicron: Findings From the SIREN Study

## TL;DR

People who first caught the Delta variant of SARS-CoV-2 had stronger antibody responses against Omicron reinfection compared to those who first caught Alpha.

## Contribution

This study shows that the initial SARS-CoV-2 variant influences the strength of immune response against Omicron.

## Key findings

- Delta first infection led to higher neutralization titers against Omicron BA.1 and BA.2 compared to Alpha first infection.
- Neutralization responses against the Ancestral strain were higher than against other variants, regardless of first infection.
- Post-vaccination, Delta-first-infected individuals had stronger Omicron-specific antibody responses.

## Abstract

Despite the existing hybrid immunity, a sharp increase in SARS‐CoV‐2 reinfections was observed worldwide following Omicron variant emergence. We investigated whether the first infecting variant indelibly shapes serological responses against Omicron (BA.1 and BA.2) reinfection.

Participants with a sequence‐confirmed Alpha (n = 23) or Delta (n = 10) first infection before third vaccine dose (V3) that subsequently had a BA.1 or BA.2 reinfection were selected. Sera were tested for anti‐SARS‐CoV‐2 spike (anti‐S) and live virus microneutralisation (LV‐N) against Ancestral, Alpha, Delta, Omicron BA.1 and BA.2. Antibody responses and waning post‐V3 were compared by first infection variant using mixed‐effect models, as well as inferred titres days before reinfections. Individual's neutralisation responses were compared 12 weeks post‐V3, among those with Alpha and Delta primary infection.

After V3, those with Delta first infection had higher LV‐N Omicron BA.1 titres (fold difference (FD) = 2.7, p = 0.05) compared to Alpha primary infection. Participants with Delta first infection presented higher LV‐N BA.1 (FD = 1.89, p = 0.004) and LV‐N BA.2 (FD = 2.06, p = 0.001) titres pre‐Omicron reinfections. Individuals' neutralisation responses against Ancestral were higher than any other subsequent variants, regardless of first infection variant.

A previous Delta SARS‐CoV‐2 infection induced a higher serological response against a subsequent Omicron infection when compared to Alpha first infections.