Efficacy of ChAdOx1 vaccines against SARS-CoV-2 Variants of Concern Beta, Delta and Omicron in the Syrian hamster model

doi:10.21203/rs.3.rs-1343927/v1

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Efficacy of ChAdOx1 vaccines against SARS-CoV-2 Variants of Concern Beta, Delta and Omicron in the Syrian hamster model

https://doi.org/10.21203/rs.3.rs-1343927/v1

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published 08 Aug, 2022

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ChAdOx1 nCoV-19 (AZD1222) is a replication-deficient simian adenovirus–vectored vaccine encoding the spike (S) protein of SARS-CoV-2, based on the first published full-length sequence (Wuhan-1). AZD1222 was shown to have 74% vaccine efficacy (VE) against symptomatic disease in clinical trials and over 2.5 billion doses of vaccine have been released for worldwide use. However, SARS-CoV-2 continues to circulate and consequently, variants of concern (VoCs) have been detected, with substitutions in the S protein that are associated with a reduction in virus neutralizing antibody titer. Updating vaccines to include S proteins of VoCs may be beneficial over boosting with vaccines encoding the ancestral S protein, even though current real-world data is suggesting good efficacy against hospitalization and death following boosting with vaccines encoding the ancestral S protein. Using the Syrian hamster model, we evaluated the effect of a single dose of AZD2816, encoding the S protein of the Beta VoC, and efficacy of AZD1222/AZD2816 as a heterologous primary series against challenge with the Beta or Delta variant. We then investigated the efficacy of a single dose of AZD2816 or AZD1222 against the Omicron VoC. As seen previously, minimal to no viral sgRNA could be detected in lungs of vaccinated animals obtained at 5 days post inoculation, in contrast to lungs of control animals. Thus, these vaccination regimens are protective against the Beta, Delta, and Omicron VoCs in the hamster model.

Figure 1. Humoral response of Syrian hamsters vaccinated with a single dose of AZD2816, a prime dose of AZD1222 and boost dose of AZD2816, or a prime-boost regimen of ChAdOx1 GFP.

Figure 2. Vaccination of Syrian hamsters with AZD2816 or AZD1222 followed by AZD2816 reduces lower respiratory tract infection by the Beta VoC.

Figure 4. Vaccination of Syrian hamsters with AZD2816 or AZD1222 followed by AZD2816 reduces lower respiratory tract infection by the Delta VoC.

Figure 7. Effects of intranasal challenge with the Omicron VoC on tracheal tissue in vaccinated and control hamsters at day 3 and 5 post challenge.

Extended Data Figure 2. Humoral response of vaccinated hamsters upon challenge with the Beta (left panels) or Delta (right panels) VoC.

Extended Data Figure 3. Linear correlation plots between sgRNA load in oropharyngeal swabs and antibodies found in serum at day of necropsy post Beta challenge.

Extended Data Figure 5. Linear correlation plots between sgRNA load in oropharyngeal swabs and antibodies found in serum at day of necropsy post Delta challenge.

Yes there is potential Competing Interest. Sarah Gilbert is a co-founder and stock-holder of Vaccitech and named as an inventor on a patent covering the use of ChAdOx1-vector-based vaccines and a patent application covering a SARS-CoV-2 (nCoV-19) vaccine (UK patent application no. 2003670.3). Teresa Lambe is named as an inventor on a patent application covering a SARS-CoV-2 (nCoV-19) vaccine (UK patent application no. 2003670.3). The University of Oxford and Vaccitech, having joint rights in the vaccine, entered into a partnership with AstraZeneca in April 2020 for further development, large-scale manufacture and global supply of the vaccine. Equitable access to the vaccine is a key component of the partnership. Neither Oxford University nor Vaccitech will receive any royalties during the pandemic period or from any sales of the vaccine in developing countries. All other authors declare no competing interests.

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published 08 Aug, 2022

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Efficacy of ChAdOx1 vaccines against SARS-CoV-2 Variants of Concern Beta, Delta and Omicron in the Syrian hamster model

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