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Authors: Paul F. McKay et al.

Link to paper: https://www.biorxiv.org/content/10.1101/2020.04.22.055608v1

Journal/ Pre-Print: BioRxiv

Tags: Drug discovery/Drug repurpose, Immunology/Immunity, Inflammation, Vaccines

Research Highlights 

1. Two immunizations of self-amplifying RNA (saRNA) encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle (LNP) induced high SARS-CoV-2 specific IgG antibodies in mice.

2. Vaccination of mice with saRNA LNP lead to efficient and linear viral neutralization of a pseudotyped HIV virus expressing the stabilised pre-fusion spike protein. It induced comparable SARS-CoV-2-specific ELISA IgG titers to recovered COVID-19 patients, and apparently higher pseudovirus neutralization titers.

3. The saRNA LNP vaccine induced a robust cellular and secreted multifunctional cytokine response in mice.

Summary 

This works briefly characterises a vaccine based on lipid nanoparticle-encapsulated saRNA encoding the SARS-CoV-2 spike protein stabilised in a pre-fusion conformation. The prototype elicited higher titers of specific antibodies in vaccinated mice and the neutralization potency appeared higher compared to convalescent human sera. Vaccination with saRNA LNP led to the induction of a cellular response characterised after in vitro antigen restimulation by secretion of multiple Th1, Th2 and Th17 cytokines.

Impact for SARS-CoV2/COVID19 research efforts

Develop a vaccine for SARS-CoV2/COVID19

Study Type

· In vitro study

· In vivo study (mouse)

· Clinical Samples study (Recovered COVID-19 patient samples)

Strengths and limitations of the paper

Novelty:

Although the platform of LNP for producing vaccines is already known, the authors present the incorporation of the saRNA as a potential new application and with higher potency. They also highlight its potential use in the context of the global SARS-CoV-2 pandemic.

Standing in the field:

The use of lipid nanoparticles for vaccination in general, but also specifically against SARS-CoV-2 is a promising approach. For instance, a phase I clinical trial recently started, in which a mRNA-based vaccine against SARS-CoV-2 is encapsulated in lipid nanoparticles (developed by Moderna and the Vaccine Research Center at the National Institutes of Health, ClinicalTrials.gov: NCT04283461).

Appropriate statistics: Yes, 2-way ANOVA adjusted for multiple comparisons or Kruskal Wallis adjusted for multiple comparisons.

Viral model used:

· Synthesis of a saRNA encoding the SARS-CoV-2 spike protein stabilised in the pre-fusion conformation, which represents the antigen producing neutralizing antibody responses. The authors used SARS-CoV-2 (GenBank accession number: QHD43416.1, modification by proline substitutions of K968 and V969 to stabilize the pre-fusion state of the spike glycoprotein).

· Use of other HIV pseudotyped viruses, including SARS-CoV, MERS-CoV and 229E-CoV.

Translatability:

The data provides information about the antigen design, formulation and preclinical evaluation and immunogenicity of a potential vaccine that could be translated to clinic. However, some aspects (e.g. antibody dependent enhancement) remain to be studied.

Main limitations:

The study of the cellular immune response was only based on the analysis of whole splenocytes and not individual immune cell types.