Spike-based DNA vaccine shows excellent protection against SARS-CoV-2 in a hamster model


A study conducted at the United States Army Research Institute of Infectious Diseases shows how a relatively simple full-length DNA vaccine against the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can elicit a neutralizing antibody response in a animal model – even after a single shot with simple jet injection technique. These exciting results are currently available on bioRxiv * prepress server.

The coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2, has prompted unprecedented global research to develop an effective vaccine. Almost every conceivable vaccine platform has been tried as a solution, including RNA and DNA-based vaccines.

Such nucleic acid-based vaccines can be produced relatively quickly once a target immunogenic sequence is known and can also be modified in line with potential changes in the sequence. However, how to deliver nucleic acids to target cells for immunogen expression is a relevant technical question.

Until now, the administration of RNA vaccines requires formulations with lipid nanoparticles or other modalities that protect the genetic material and can transmit it across cell membranes. The safety and efficacy of such RNA vaccines are currently being evaluated in various COVID vaccine studies.

On the other hand, DNA delivered via needle and syringe can be immunogenic without the use of lipid nanoparticles, even in non-human primates. Other techniques (eg, electroporation or jet injection) can further increase immunogenicity while reducing dosage requirements.

Recently, a research team led by Dr. Rebecca L. Brocato of the Division of Virology of the U.S. Army’s Infectious Disease Research Institute decided to establish a proof-of-concept for using the SARS DNA vaccine. -CoV-2 jet injected using both wild and transiently immunosuppressed hamsters as animal models.

G) nCoV-S (JET) DNA, H) PBS o I) criceti vaccinati con MERS-CoV dove il viola indica aree di consolidamento.  ISH per rilevare l'RNA genomico SARS-CoV-2 in sezioni polmonari di criceti vaccinati con J) nCoV-S (JET), K) PBS e L) MERSCoV.  È stata rilevata un'etichettatura rara e positiva in sezioni polmonari di criceto vaccinate con DNA di nCoV-S (JET) (frecce).  Gli asterischi indicano che i risultati erano statisticamente significativi, come segue: *, P <0,05;  **, P <0,01;  ***, P <0,001;  ns, non significativo.  Barre della scala = 400 micron.

G) nCoV-S (JET) DNA, H) PBS or I) MERS-CoV vaccinated hamsters where purple indicates areas of consolidation. ISH to detect SARS-CoV-2 genomic RNA in lung sections of hamsters vaccinated with J) nCoV-S (JET), K) PBS and L) MERSCoV. Rare and positive labeling was found in hamster lung sections vaccinated with nCoV-S DNA (JET) (arrows). The asterisks indicate that the results were statistically significant, as follows: *, P <0.05; **, P <0.01; ***, P <0.001; ns, not significant. Scale bars = 400 microns.

Construction of clones and evaluation of immunogenicity

In this study, the scientists used a jet injection technique to deliver a SARS-CoV-2 spike-based DNA vaccine to Syrian hamsters. Because jet injection technology is not widely available for use in small animals, they leveraged human intradermal jet injections to administer intramuscular vaccines to hamsters.

Their specific SARS-CoV-2 spike-based DNA vaccine, known as nCoV-S (JET), was constructed by cloning a human codon-optimized gene that encodes the full-length spike protein into a plasmid vector. Additionally, the plasmid backbone used for this vaccine was previously used for hantavirus DNA vaccines which are currently in Phase 1 and 2 clinical trials.

The primary immunogenicity parameters at the center of this research were neutralizing antibodies. More specifically, the researchers measured neutralizing antibodies against live virus using the Plaque Reduction Neutralization Test (PRNT) and a non-replicating vesicular stomatitis virus (VSV) (PsVNA) -based pseudovirion neutralization test.

A robust protective effect

Briefly, the data obtained indicate that the neutralizing antibodies induced by the nCoV-S (JET) vaccine in hamsters and conferred protection in both wild-type and transiently immunosuppressed hamster models.

More specifically, a protective effect was also observed in the SARS-CoV-2 infection model with severe and prolonged disease in immunosuppressed animals prior to exposure to the virus. In contrast, the unprotected animals lost more than 15% of their weight and still had infectious viral particles in their lungs nearly two weeks after exposure.

In addition, neutralizing antibody levels increased substantially after the booster vaccination, with titers comparable to or higher than those found in other DNA vaccines evaluated in primates and non-human mice.

Finally, in the case of this new nCoV-S DNA vaccine (JET), the normal proliferation pattern of immune T or B cells at the time of exposure was not a prerequisite for obtaining the protective effect.

Unveiling the potential for further research

Simply put, this study demonstrates how a relatively simple, unmodified full-length DNA vaccine administered with a relatively simple jet injection technique can actually elicit neutralizing antibodies after a single vaccination, but also significantly increase antibody titers after a shot. booster and protect from SARS -CoV-2 in two hamster models.

“Our results in the hamster model with transient immunosuppression add further credibility to the idea that antibodies are playing an important role in the observed protection,” the study authors further emphasize in this paper. bioRxiv paper.

This undoubtedly reveals a great potential of this approach to move to the next stage of preclinical studies and introduces Syrian hamsters as a viable disease model; however, further studies are needed to evaluate these innovative research steps.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice / health-related behavior, or treated as consolidated information.


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