Another mRNA-based vaccine candidate protects animals against SARS-CoV-2

July 24, 2020

An experimental messenger RNA (mRNA)-based vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicits protective immune responses in mice and non-human primates, researchers report on July 23rd in the journal Cell. Two injections of the vaccine were sufficient to induce robust immunity, completely preventing SARS-CoV-2 infection in mice.

"The robust protection observed in the present studies and the clear immune correlates of protection pave the path forward for future COVID-19 vaccine development in humans," says senior study author Cheng-Feng Qin of the Beijing Institute of Microbiology and Epidemiology.

mRNA-based vaccines are attractive options for protecting against SARS-CoV-2 because they can be rapidly designed and manufactured at a large scale within weeks. Moreover, preclinical studies have demonstrated that mRNA-based vaccines induce potent and broadly protective immune responses against various pathogens with an acceptable safety profile.

In the Cell study, Qin and his colleagues developed a vaccine consisting of mRNA that encodes the receptor-binding domain (RBD) of the spike (S) protein, which is located on the surface of SARS-CoV-2. The vaccine, named ARCoV, is encapsulated in lipid nanoparticles, which improves delivery into tissues.

Targeting RBD rather than the entire S protein may represent a safer option, potentially triggering the production of fewer non-neutralizing antibodies. These antibodies could enhance viral entry into cells and viral replication through a process called antibody-dependent enhancement of infection, which has been previously reported for the related virus SARS-CoV--the causative agent of the SARS outbreak in 2002 to 2003.

The researchers injected ARCoV into the muscle tissue of 16 mice and provided a booster shot two weeks later. The vaccine elicited the production of high levels of neutralizing antibodies, which protect host cells by preventing the virus from interacting with them. These antibodies were cross-reactive, offering broad protection against three different strains of SARS-CoV-2. In addition, the vaccine increased the number of T cells in the spleen.

Mice that received two doses of ARCoV and were exposed to SARS-CoV-2 35 days later showed no signs of viral RNA in the lungs or trachea and no lung damage or inflammation. Results from 20 cynomolgus monkeys showed that two ARCoV doses induced a virus-specific T cell response and the production of neutralizing antibodies at levels that far exceed those seen in most recovered COVID-19 patients. Moreover, none of the vaccinated animals experienced adverse effects.

To assess the thermal stability of ARCoV, the researchers stored the vaccine at various temperatures for one, four, or seven days, injected it into mice, and visualized its tissue distribution. The results showed that the vaccine was effectively delivered to tissues, achieving the same high level of expression after being stored at room temperature for one week, without any signs of decreased activity. "A ready-to-use and thermostable vaccine like ARCoV is highly desirable to eliminate the need for cold-chain transportation," Qin says.

The researchers are currently evaluating the long-term stability of ARCoV. "In addition, the duration of neutralization antibody induced by ARCoV is yet to be determined, as experience from other human coronaviruses has indicated the possibility of re-infection due to waning of the antibody response," Qin says. "Future studies are needed to evaluate the long-term immune response in animal models and the effectiveness of ARCoV in humans."
-end-
This work was supported by the National Key Research and Development Project of China, the National Science Fund for Distinguished Young Scholars, the National Natural Science Foundation of China, and the Chinese Academy of Medical Sciences. There are pending patent applications related to the ARCoV mRNA vaccine, and several co-authors are employees of Suzhou Abogen Biosciences.

Cell, Zhang, Li, Deng, Zhao, Huang, Yang, and Huang et al.: "A thermostable mRNA vaccine against COVID-19" https://www.cell.com/cell/fulltext/S0092-8674(20)30932-6

Cell (@CellCellPress), the flagship journal of Cell Press, is a bimonthly journal that publishes findings of unusual significance in any area of experimental biology, including but not limited to cell biology, molecular biology, neuroscience, immunology, virology and microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. Visit: http://www.cell.com/cell. To receive Cell Press media alerts, contact press@cell.com.

Cell Press

Related Antibodies Articles from Brightsurf:

Scientist develops new way to test for COVID-19 antibodies
New research details how a cell-free test rapidly detects COVID-19 neutralizing antibodies and could aid in vaccine testing and drug discovery efforts.

Mussels connect antibodies to treat cancer
POSTECH research team develops innovative local anticancer immunotherapy technology using mussel protein.

For an effective COVID vaccine, look beyond antibodies to T-cells
Most vaccine developers are aiming solely for a robust antibody response against the SARS-CoV-2 virus, despite evidence that antibodies are not the body's primary protective response to infection by coronaviruses, says Marc Hellerstein of UC Berkeley.

Children can have COVID-19 antibodies and virus in their system simultaneously
With many questions remaining around how children spread COVID-19, Children's National Hospital researchers set out to improve the understanding of how long it takes pediatric patients with the virus to clear it from their systems, and at what point they start to make antibodies that work against the coronavirus.

The behavior of therapeutic antibodies in immunotherapy
Since the late 1990s, immunotherapy has been the frontline treatment against lymphomas where synthetic antibodies are used to stop the proliferation of cancerous white blood cells.

Re-engineering antibodies for COVID-19
Catholic University of America researcher uses 'in silico' analysis to fast-track passive immunity

Seroprevalence of antibodies to SARS-CoV-2 in 10 US sites
This study estimates how common SARS-CoV-2 antibodies are in convenience samples from 10 geographic sites in the United States.

Neutralizing antibodies in the battle against COVID-19
An important line of defense against SARS-CoV-2 is the formation of neutralizing antibodies.

Three new studies identify neutralizing antibodies against SARS-CoV-2
A trio of papers describes several newly discovered human antibodies that target the SARS-CoV-2 virus, isolated from survivors of SARS-CoV-2 and SARS-CoV infection.

More effective human antibodies possible with chicken cells
Antibodies for potential use as medicines can be made rapidly in chicken cells grown in laboratories.

Read More: Antibodies News and Antibodies Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.