Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA-SARS-2-S in preclinical vaccination

Abstract

Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) has emerged as the infectious agent causing the pandemic coronavirus disease 2019 (COVID-19) with dramatic consequences for global human health and economics. Previously, we reached clinical evaluation with our vector vaccine based on modified vaccinia virus Ankara (MVA) against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes an infection in humans similar to SARS and COVID-19. Here, we describe the construction and preclinical characterization of a recombinant MVA expressing full-length SARS-CoV-2 spike (S) protein (MVA-SARS-2-S). Genetic stability and growth characteristics of MVA-SARS-2-S, plus its robust expression of S protein as antigen, make it a suitable candidate vaccine for industrial-scale production. Vaccinated mice produced S-specific CD8+ T cells and serum antibodies binding to S protein that neutralized SARS-CoV-2. Prime-boost vaccination with MVA-SARS-2-S protected mice sensitized with a human ACE2-expressing adenovirus from SARS-CoV-2 infection. MVA-SARS-2-S is currently being investigated in a phase I clinical trial as aspirant for developing a safe and efficacious vaccine against COVID-19.

Intranasal Administration of a Monoclonal Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection

“…Four days post challenge, the mice were euthanized, and the lungs were collected for viral load determination and histological analyses. Neither significant body weight changes nor clinical symptoms were observed in any of the groups ( Figure S7 ), which is in line with previous reports of hACE2- transduced mice [ 32 , 49 ]. Importantly, this result indicated that the presence of DZIF-10c did not induce antibody-dependent enhancement (ADE).…”

“…Since mice are naturally not susceptible to SARS-CoV-2 infection due to incompatibility of the S protein to murine ACE2 [ 44 , 45 , 46 ], we transduced BALB/c mice intratracheally with an adenoviral vector carrying the genetic information for hACE2 and the reporter mCherry (Ad_ACE2-mCherry). This approach is based on a previously published model for middle east respiratory syndrome coronavirus (MERS-CoV) [ 29 , 30 ] and has been shown to be suitable for modeling SARS-CoV-2 infection and preclinical testing of a SARS-CoV-2 vaccine candidate [ 32 ]. Moreover, this model was used successfully by several other groups to study SARS-CoV-2 pathogenesis and antiviral interventions [ 22 , 47 , 48 ].…”

“…All challenge animal experiments were performed in accordance with the German animal protection laws and were authorized by the regional authorities (RP Gießen, G44/2020). The hACE2 transduction mouse model for SARS-CoV-2 and associated procedures were designed based on a previously established model for MERS-CoV [ 29 , 30 , 31 ] and were described recently [ 32 ]. Briefly, 6–8 week old BALB/c mice were purchased from Charles River Laboratories and housed under specific pathogen-free conditions in isocages in the animal facility at the Institute of Virology Marburg.…”

Synthetic Multiantigen MVA Vaccine COH04S1 Protects Against SARS-CoV-2 in Syrian Hamsters and Non-Human Primates

“…Although several SARS-CoV-2 vaccines based on MVA have been developed and evaluated in animal models for immunogenicity and efficacy 29,58–61 , there is currently no MVA-based SARS-CoV-2 vaccine approved for routine clinical use. COH04S1 and MVA-SARS-2-S, an MVA vector expressing S alone, are currently the only MVA-based SARS-CoV-2 vaccines that are clinically evaluated 61 .…”

Modified Vaccinia Virus Ankara as a Viral Vector for Vaccine Candidates against Chikungunya Virus

“…With the SARS-CoV-2/COVID-19 pandemic affecting the world population and, to fight the disease, many different vaccine strategies have been developed, and several of these vaccines have shown high efficacy in humans [ 54 ]. One type of vaccine candidate is based on recombinant MVA, which has shown good immunogenicity profiles and high efficacy against SARS-CoV-2 in preclinical trials [ 55 , 56 , 57 , 58 , 59 ], supporting further development in clinical trials. It remains to be defined how far MVA-expressing SARS-CoV-2 antigens will move forward against COVID-19 (ClinicalTrials.gov), but it will be a good opportunity to evaluate the effectiveness and long-term durability, a feature of smallpox vaccination [ 1 ].…”