Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters

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Abstract

Vaccines play a critical role in combating the COVID-19 pandemic. Future control of the pandemic requires improved vaccines with high efficacy against newly emerging SARS-CoV-2 variants and the ability to reduce virus transmission. Here we compare immune responses and preclinical efficacy of the mRNA vaccine BNT162b2, the adenovirus-vectored spike vaccine Ad2-spike and the live-attenuated virus vaccine candidate sCPD9 in Syrian hamsters, using both homogeneous and heterologous vaccination regimens. Comparative vaccine efficacy was assessed by employing readouts from virus titrations to single-cell RNA sequencing. Our results show that sCPD9 vaccination elicited the most robust immunity, including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue after challenge with heterologous SARS-CoV-2. Overall, our results demonstrate that live-attenuated vaccines offer advantages over currently available COVID-19 vaccines.

Article activity feed

  1. Rachel Palinski

    Review 2: "A live attenuated vaccine offers superior mucosal and systemic immunity to SARS-CoV-2"

    This preprint reports improved immune responses to and efficacy of a live attenuated SARS-CoV-2 vaccine, compared to Pfizer mRNA vaccine, and an adenovirus-vectored spike protein vaccine (Ad2) in hamsters. Reviewers find the study significant, with the data presented as reliable.

  2. Qiuhong Wang, Mingde Liu

    Review 1: "A live attenuated vaccine offers superior mucosal and systemic immunity to SARS-CoV-2"

    This preprint reports improved immune responses to and efficacy of a live attenuated SARS-CoV-2 vaccine, compared to Pfizer mRNA vaccine, and an adenovirus-vectored spike protein vaccine (Ad2) in hamsters. Reviewers find the study significant, with the data presented as reliable.

  3. SciScore for 10.1101/2022.05.16.492138: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsField Sample Permit: All animal experiments were performed in compliance with relevant institutional, national, and international guidelines for care and humane use of animal and approved by the Landesamt für Gesundheit und Soziales in Berlin, Germany (permit number 0086/20).
    Sex as a biological variableHamsters were randomly assigned into groups, with 50 – 60 % of the animals in each group being female.
    RandomizationHamsters were randomly assigned into groups, with 50 – 60 % of the animals in each group being female.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antigen retrieval was performed using microwave …