We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us

Download Mobile App





Linear-DNA Forms of COVID-19 Vaccine Candidates Show Strong Antibody and T-Cell Responses in Preclinical Trials

By HospiMedica International staff writers
Posted on 20 Jul 2020
Print article
Illustration
Illustration
A group of linear-DNA forms of COVID-19 vaccine candidates under development has yielded strong antibody and T-cell responses even at very low doses of linear DNA in preclinical trials, raising the potential of effective dosing empowering global utility.

Linear DNA vaccines offer a broad array of advantages: stability during storage and shipment, the capacity to manufacture both centrally and locally across the globe, vaccine expression without apparent integration into the patient’s genome, the avoidance of antibiotics, no risk of transference of antibiotic-resistance genes, the avoidance of bacterial vectors, high purity and simplicity of production, and apparent high efficacy. In preclinical trials, five LineaDNA vaccine candidates being developed by Applied DNA Sciences Inc. (Stony Brook, NY, USA) in association with Takis Biotech (Rome, Italy) have demonstrated evidence of production of antibodies and T cell responses in mice.

BALB/c mice received linear DNA at day 1 and a booster vaccination on day 21. All animals demonstrated seroconversion to producing IgG against SARS-CoV-2 Spike Protein already by day 14, and significantly enhanced responses by day 38. Five different candidates of linear synthetic genomic constructs of the S gene that encode for the Spike protein were evaluated. The five constructs were designed for optimal expression in muscle and maximal immunogenicity after vaccination.

Titration studies showed that even at dilutions of 1:50,000, antisera derived from mice vaccinated with linear DNA retained its binding activity. IgGs against SARS-CoV-2 Spike could be readily identified in bronchoalveolar lavage, a wash of the lower respiratory system, suggesting that vaccination in mouse muscle would allow the consequent antibodies to fight the infection in the lower lung. T-cell responses to the linear vaccines were strongest for the linear construct that contained the sequence corresponding to an abbreviated form of the Spike protein, specifically the portion of Spike that binds to the receptor on human cells that mediates viral uptake into the host’s epithelial cells in the respiratory system. The T-cell response involved both the CD4+ and CD8+ lineages, suggesting that the response may survive long term.

In plasmid format, these same vaccine candidates were the first reported to elicit neutralizing antibodies that prevented uptake of SARS-CoV-2 when human cells in culture were challenged by the functional virus in the presence of the mouse antisera. Similar neutralization studies are scheduled to begin shortly for the antisera produced by the linear DNA constructs.

The companies believe that their collaboration on linear vaccines against the disease COVID-19 offers unique advantages in the development of vaccines, and that no single vaccine will offer a universal solution to the pandemic. Given the mutational proclivity of SARS-CoV-2, and the synthetic genomic design skills of Takis, Applied DNA could manufacture an improved LineaDNA vaccine within days of obtaining the sequence of a mutant variant that dodged the vaccines targeting the currently dominant variants.

“We are pleased to report that all five LineaDNA vaccine candidates provoked seroconversion in mice with all animals producing IgG against the SARS-CoV-2 Spike Protein by Day 14 and significantly enhanced responses by Day 38. These results are consistent with IgGs that in prior studies with plasmids were neutralizing in that they prevented the uptake of functional virus by host cells in culture,” stated Dr. James A. Hayward, president and CEO of Applied DNA. “We look forward to supporting further studies by Takis with a goal of entering human trials in early Autumn. We believe no single vaccine will provide the security we need as a global population, and that our LineaDNA vaccines will complement those already marching toward the market.”

“Our results are very encouraging, and we have good reason for optimism. We must proceed with toxicology studies and move on to large animal studies as we march toward the clinic. We are now moving to engage third parties to help take us to market on the basis of these encouraging results,” said Dr. Luigi Aurisicchio, Chief Executive and Scientific Officer of Takis Biotech.

Related Links:
Applied DNA Sciences Inc.
Takis Biotech



Print article
IIR Middle East

Channels

Critical Care

view channel
Image: Size comparison of the new mTP laser array (Photo courtesy of Rockley)

New Chip Technology Paves Way for Tiny Wearable Devices to Detect and Measure Biomarkers

Scientists have developed what is believed to be the world’s first micro-transfer-printed (mTP) silicon-photonics-based laser for commercial applications. This groundbreaking achievement by Rockley Photonics... Read more

Surgical Techniques

view channel
Image: The EASEE minimally invasive brain pacemaker has received CE certification (Photo courtesy of Precisis GmbH)

World's First Minimally Invasive Brain Pacemaker Treats Epilepsy

The treatment of patients with epilepsy always begins with medication. However, for decades there has unfortunately been a consistently large group of around 30% of all patients for whom pharmacological... Read more

Patient Care

view channel
Image: The biomolecular film can be picked up with tweezers and placed onto a wound (Photo courtesy of TUM)

Biomolecular Wound Healing Film Adheres to Sensitive Tissue and Releases Active Ingredients

Conventional bandages may be very effective for treating smaller skin abrasions, but things get more difficult when it comes to soft-tissue injuries such as on the tongue or on sensitive surfaces like... Read more

Health IT

view channel
Image: Using digital data can improve health outcomes (Photo courtesy of Unsplash)

Electronic Health Records May Be Key to Improving Patient Care, Study Finds

When a patient gets transferred from a hospital to a nearby specialist or rehabilitation facility, it is often difficult for personnel at the new facility to access the patient’s electronic health records... Read more
Copyright © 2000-2022 Globetech Media. All rights reserved.