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Authors: Di Yin et al

Link to paper: https://doi.org/10.1101/2020.05.14.093054

Journal/ Pre-Print: Biorxiv

Tags: Immunology/Immunity, Vaccines

Research Highlights 

1. Creation of lentiviral particles with SARS-CoV-2 Spike (S) glycoprotein encoding mRNA inside and expressing both S and VSV-G surface fusion proteins, named ShaCoVacc.

2. Two weeks post ShaCoVacc administration, neutralizing IgG antibodies against S were found in mouse sera.

3. Neutralizing antibody epitopes were mapped on S using a linear peptide array

Summary 

The authors created virus like particles (VLPs) from lentiviruses with S-encoding mRNA inside and both S and VSV-G fusion protein expressed on their surface. S was altered so that it expressed 6X MS2 stem loop repeats allow S mRNA to be packaged into VLPs via interaction with MS2 coat fused GagPol. Additionally, two proline substitution mutations in S2 were made designed to increase S stability and expression. Transcription and translation was enhanced by using a CMV promoter, codon-optimization of the S sequence and a signal peptide from the human heavy chain of IgE. Two weeks post single-administration of ShaCoVacc, neutralizing serum antibodies against S were detected.

Impact for SARS-CoV2/COVID19 research efforts

Develop a vaccine for SARS-CoV-2/COVID19

Study Type

· In vitro study

· In vivo study (mouse)

Strengths and limitations of the paper

Novelty: First vaccine platform that incorporates whole S glycoprotein and its mRNA (in a non-reproducing lentiviral-like particle). Mapping of serum responses using a linear peptide array, primarily located in the S receptor binding domain, is novel.

Standing in the field: A single dose was sufficient to elicit neutralizing antibody production in mice, although other vaccines have already been tested in macaques.

Appropriate statistics: Authors do not state whether data points represent technical or biological replicates in Figure 1. A non-parametric test would have been more appropriate for comparing groups of 3.

Viral model used: ShaCoVacc - lentiviral-like particle with modified SARS-CoV-2 S.

Translatability: lentiviral production has been used in GCP settings for CAR T cell therapy, so could be translated to clinical use. However, immunogenicity and protection from viral challenge in macaques, and investigation of the cellular and cytokine response additional to antibody production would be desirable.

Main limitations: Analysis in mice and cell lines only.

Lack of quantification and EM morphological characterization of S on VLPs.

Lack of characterization of the cellular and cytokine response to immunization.

Mapping of neutralizing antibody responses limited to linear peptides.