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Omicron breakthrough infections in vaccinated or previously infected hamsters

View ORCID ProfileJie Zhou, View ORCID ProfileKsenia Sukhova, View ORCID ProfilePaul F. McKay, View ORCID ProfileAshwini Kurshan, Yeuk Yau, Thomas Lechmere, View ORCID ProfileJonathan C. Brown, Maya Moshe, View ORCID ProfileRuthiran Kugasathan, View ORCID ProfileLuke B. Snell, View ORCID ProfileJonathan D. Edgeworth, View ORCID ProfileRobin J. Shattock, View ORCID ProfileKatie J. Doores, View ORCID ProfileThomas P. Peacock, View ORCID ProfileWendy S. Barclay
doi: https://doi.org/10.1101/2022.05.20.492779
Jie Zhou
1Department of Infectious Disease, Imperial College London; London, UK
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Ksenia Sukhova
1Department of Infectious Disease, Imperial College London; London, UK
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Paul F. McKay
1Department of Infectious Disease, Imperial College London; London, UK
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Ashwini Kurshan
2Department of Infectious Diseases, School of Immunology & Microbial Sciences, King’s College London; London, UK
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Yeuk Yau
2Department of Infectious Diseases, School of Immunology & Microbial Sciences, King’s College London; London, UK
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Thomas Lechmere
2Department of Infectious Diseases, School of Immunology & Microbial Sciences, King’s College London; London, UK
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Jonathan C. Brown
1Department of Infectious Disease, Imperial College London; London, UK
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Maya Moshe
1Department of Infectious Disease, Imperial College London; London, UK
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Ruthiran Kugasathan
1Department of Infectious Disease, Imperial College London; London, UK
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Luke B. Snell
3Centre for Clinical Infection and Diagnostics Research, Department of Infectious Diseases, Guy’s and St Thomas’ NHS Foundation Trust; London, UK
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Jonathan D. Edgeworth
3Centre for Clinical Infection and Diagnostics Research, Department of Infectious Diseases, Guy’s and St Thomas’ NHS Foundation Trust; London, UK
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Robin J. Shattock
1Department of Infectious Disease, Imperial College London; London, UK
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Katie J. Doores
2Department of Infectious Diseases, School of Immunology & Microbial Sciences, King’s College London; London, UK
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Thomas P. Peacock
1Department of Infectious Disease, Imperial College London; London, UK
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Wendy S. Barclay
1Department of Infectious Disease, Imperial College London; London, UK
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  • For correspondence: w.barclay@imperial.ac.uk
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Abstract

The second and third years of the SARS-CoV-2 pandemic have been marked by the repeated emergence and replacement of ‘variants’ with genetic and phenotypic distance from the ancestral strains, the most recent examples being Delta and Omicron. Here we describe a hamster contact exposure challenge model to assess protection conferred by vaccination or prior infection against re-infection. We found that 2-doses of self-amplifying RNA vaccine based on the ancestral spike ameliorated weight loss following Delta infection and decreased viral loads, but had minimal effect on Omicron/BA.1 infection. Prior infection with ancestral or Alpha variant was partially protective against Omicron/BA.1 infection, whereas all animals previously infected with Delta and exposed to Omicron became infected, although shed less virus. We further tested whether prior infection with Omicron/BA.1 protected from re-infection with Delta or Omicron/BA.2. Omicron/BA.1 was protective against Omicron/BA.2, but not Delta reinfection, again showing Delta and Omicron have a very large antigenic distance. Indeed, cross-neutralisation assays with human antisera from otherwise immunonaïve individuals (unvaccinated and no known prior infection), confirmed a large antigenic distance between Delta and Omicron. Prior vaccination followed by Omicron or Delta breakthrough infection led to a higher degree of cross-reactivity to all tested variants. To conclude, cohorts whose only immune experience of COVID is Omicron/BA.1 infection may be particularly vulnerable to future circulation of Delta or Delta-like derivatives. In contrast, repeated exposure to antigenically distinct spikes, via infection and or vaccination drives a more cross-reactive immune response, both in hamsters and people.

One Sentence Summary Infection with the Delta and Omicron SARS-CoV-2 variants do not provide cross-protective immunity against reinfection with one another in hamsters.

Competing Interest Statement

Robin Shattock and Paul McKay and are co-inventors on a patent application covering this SARS-CoV-2 self-amplifying RNA vaccine. All other authors have nothing to declare.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 20, 2022.
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Omicron breakthrough infections in vaccinated or previously infected hamsters
Jie Zhou, Ksenia Sukhova, Paul F. McKay, Ashwini Kurshan, Yeuk Yau, Thomas Lechmere, Jonathan C. Brown, Maya Moshe, Ruthiran Kugasathan, Luke B. Snell, Jonathan D. Edgeworth, Robin J. Shattock, Katie J. Doores, Thomas P. Peacock, Wendy S. Barclay
bioRxiv 2022.05.20.492779; doi: https://doi.org/10.1101/2022.05.20.492779
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Omicron breakthrough infections in vaccinated or previously infected hamsters
Jie Zhou, Ksenia Sukhova, Paul F. McKay, Ashwini Kurshan, Yeuk Yau, Thomas Lechmere, Jonathan C. Brown, Maya Moshe, Ruthiran Kugasathan, Luke B. Snell, Jonathan D. Edgeworth, Robin J. Shattock, Katie J. Doores, Thomas P. Peacock, Wendy S. Barclay
bioRxiv 2022.05.20.492779; doi: https://doi.org/10.1101/2022.05.20.492779

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