Abstract
Second-generation COVID-19 vaccines could contribute to establish protective immunity against SARS-CoV-2 and its emerging variants. We developed COH04S1, a synthetic multiantigen modified vaccinia Ankara-based SARS-CoV-2 vaccine that co-expresses spike and nucleocapsid antigens. Here, we report COH04S1 vaccine efficacy in animal models. We demonstrate that intramuscular or intranasal vaccination of Syrian hamsters with COH04S1 induces robust Th1-biased antigen-specific humoral immunity and cross-neutralizing antibodies (NAb) and protects against weight loss, lower respiratory tract infection, and lung injury following intranasal SARS-CoV-2 challenge. Moreover, we demonstrate that single-dose or two-dose vaccination of non-human primates with COH04S1 induces robust antigen-specific binding antibodies, NAb, and Th1-biased T cells, protects against both upper and lower respiratory tract infection following intranasal/intratracheal SARS-CoV-2 challenge, and triggers potent post-challenge anamnestic antiviral responses. These results demonstrate COH04S1-mediated vaccine protection in animal models through different vaccination routes and dose regimens, complementing ongoing investigation of this multiantigen SARS-CoV-2 vaccine in clinical trials.
Highlights
Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China at the end of 2019, SARSCoV-2 has spread rapidly worldwide, causing a global pandemic with millions of fatalities[1,2]
neutralizing antibodies (NAb) titers were measured in serum samples of vaccine and control groups post-first (d28) and post-second (d42) immunization via Plaque reduction neutralization titer (PRNT) assay against SARS-CoV-2 infectious virus
We demonstrate that COH04S1 stimulates protective immunity against SARS-CoV-2 in Syrian hamsters by intramuscular (IM) and intranasal (IN) vaccination and in nonhuman primates (NHP) through two-dose (2D) and single-dose (1D) vaccination regimens
Summary
Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China at the end of 2019, SARSCoV-2 has spread rapidly worldwide, causing a global pandemic with millions of fatalities[1,2]. Several SARS-CoV-2 vaccines were developed in response to the COVID-19 pandemic with unprecedented pace and showed 62–95% efficacy in Phase 3 clinical trials, leading to their emergency use authorization (EUA) in many countries by the end of 2020/beginning of 20213–8 This includes vaccines based on mRNA, adenovirus vectors, and nanoparticles that utilize different antigenic forms of the spike (S) protein to induce protective immunity against SARS-CoV-2 primarily through the function of neutralizing antibodies (NAb)[9,10,11,12]. Immunization of mice with these vaccine vectors resulted in the stimulation of potent SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent NAb29 One of these sMVA vector constructs forms the basis of clinical vaccine candidate. Phase 1 trial in healthy adults (NCT04639466), and is currently evaluated in a randomized, double-blinded, single center Phase 2
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