# Differential efficacy of first licensed western vaccines protecting without immunopathogenesis Wuhan-1-challenged hamsters from severe COVID-19

## TL;DR

This study compares how well early Western-approved vaccines protect hamsters from severe COVID-19 without causing harmful immune reactions.

## Contribution

The study demonstrates that early licensed vaccines prevent severe disease and avoid vaccine-associated immunopathogenesis in a hamster model.

## Key findings

- All authorized vaccines induced neutralizing antibodies and protected against severe disease in hamsters.
- Adenoviral vaccines induced neutralizing antibodies after a single dose, while mRNA vaccines required a booster.
- Alum-adjuvanted Spike protein caused vaccine-associated enhanced respiratory disease (VAERD), unlike the commercial vaccines.

## Abstract

Four COVID-19 vaccines were developed, tested, and authorized early in Europe and the US. Comirnaty and Spikevax are mRNA-based, whereas Jcovden and Vaxzevria utilize adenoviral vectors (AdV). We described a hamster model of COVID-19 utilizing Wuhan-1 strain SARS-CoV-2, in which vaccine-associated immunopathogenesis can be induced by Alum-adjuvanted Spike protein (Alum+S). Such animals were vaccinated with the authorized vaccines or Alum+S, challenged, and examined. All vaccinated hamsters produced antibodies targeting S. Neutralizing antibodies (nAb) were induced only by authorized vaccines. While nAbs were present after one vaccination with AdV-vaccines, mRNA vaccines needed a boost immunization. Upon challenge, all authorized vaccines protected from severe disease. Less tissue damage and no live virus (one exception) were detectable in the lungs. In contrast, Alum+S immunized hamsters developed VAERD. Our data reveal the absence of induction of VAERD by early commercial vaccines in hamsters, while animals´ immune responses and protection seem to match the clinical vaccine efficacy.