Hopeful COVID-19 research: Testing new vaccines, repurposing old ones

We continue our Hope Behind the Headlines series. This week, we track the progress of a newly developed vaccine, examine the benefits of repurposing existing vaccines, and see how a synthetic antibody can “distract” and neutralize the new coronavirus before it reaches healthy cells.

Medical News Today previously reported on the research that Sarah Gilbert, a professor of vaccinology at Oxford University’s Jenner Institute in the United Kingdom, led on a potential vaccine.

The recombinant vaccine that the team developed uses a chimpanzee adenovirus (called ChAdOx1) that is harmless to humans, inserting into it the spike protein gene of SARS-CoV-2.

As this approach to developing vaccines has been “extensively tested in other situations,” and the research group has a successful track record in this area (which includes developing a promising vaccine against MERS, a “cousin” of SARS), experts were hopeful a few months ago that Prof. Gilbert’s team would devise an effective SARS-CoV-2 vaccine.

Stay informed with live updates on the current COVID-19 outbreak and visit our coronavirus hub for more advice on prevention and treatment.

However, there were concerns about dosage. At the time, Prof. Ian Jones from the University of Reading said, “More challenging […] will be working out if the amount given is sufficient to give full protection, and if it needs one dose or two.”

2 doses of new vaccine successful in pigs 

Now, in collaboration with The Pirbright Institute in the U.K., the Jenner Institute have tested the vaccine, called the ChAdOx1 nCoV-19 vaccine, in pigs and found that two doses create a greater antibody response than one dose.

According to The Pirbright Institute, phase I of the human clinical trials has already started. The researchers are testing a single dose of ChAdOx1 nCoV-19 because research in macaque monkeys showed that a single immunization with the vaccine protected against lung disease.

Researchers are now recruiting volunteers for the next phase of human clinical trials.

The fact that two doses proved more protective than one in pigs is important because it suggests that the same might be true in humans.

It also suggests that if the results of the human clinical trials are underwhelming at one dose, upping the intervention to two doses may yield better outcomes.

“These results look encouraging that administering two injections with the same vaccine boosts antibody responses that can neutralize the virus, but it is the response in humans that is important.”

– Prof. Bryan Charleston, director of The Pirbright Institute

“The pig has proved to be a valuable model for testing human vaccines for other diseases to give an indication of the type of immune response induced and testing different doses,” Prof. Charleston continues.

“Pigs are more physiologically similar to humans than some other animal models — for example, their body weight and metabolic rate — and are more accessible than studies using nonhuman primates.”

Repurposing MMR vaccine for COVID-19

Researchers have made headway not only in developing new vaccines but also in repurposing old ones.

New research shows that the common vaccine that protects against measles, mumps, and rubella (MMR) could help prevent inflammation in COVID-19, which leads to severe symptoms.

The new study — which appears in the American Society for Microbiology’s journal mBio — is not the only one to suggest that reusing existing vaccines (initially developed for other viruses) may protect against SARS-CoV-2.

For instance, several clinical trials are currently testing whether a tuberculosis vaccine could be effective against the new coronavirus.

These research efforts are predicated on the notion that some vaccines may benefit the immune system in a nonspecific way, helping it fight the new coronavirus without explicitly training it to attack SARS-CoV-2 in particular.

The ability of the immune system to fight infection in a nonspecific way is the first line of defense against infections, and it is called the innate immune response.

Repurposing MMR vaccines in the fight against SARS-CoV-2 rests on the hypothesis that such an innate immune response can be trained.

In the case of COVID-19, and in support of their theory, the authors of the new mBio study cite the example of the 955 U.S. Navy sailors on the U.S.S. Roosevelt ship who tested positive for SARS-CoV-2 but only had mild symptoms.

The researchers believe that this is due to the fact that all U.S. Navy recruits receive the MMR vaccine. Further studies revealed lower COVID-19 mortality in areas where people receive MMR vaccinations, note the researchers.

If their hypothesis is correct, the authors say that using MMR vaccines could be a “low-risk-high-reward” approach to saving lives that COVID-19 might otherwise claim.

Dr. Paul Fidel, Jr., associate dean for research at Louisiana State University Health School of Dentistry in New Orleans, and Dr. Mairi Noverr, a professor of microbiology and immunology at Tulane University School of Medicine in New Orleans, wish to implement a clinical trial of MMR vaccines in high risk frontline healthcare workers in New Orleans.

Fidel and Noverr also received a grant to test the MMR and TB vaccines in monkeys with COVID-19.

“While we are conducting the clinical trials, I don’t think it’s going to hurt anybody to have an MMR vaccine that would protect against the measles, mumps, and rubella with this potential added benefit of helping against COVID-19.”

– Dr. Paul Fidel

Using a ‘decoy’ antibody to neutralize SARS-CoV-2

Another scientist from Tulane University, Dr. Jay Kolls, is also leading research efforts that may result in effective prevention for frontline healthcare workers and first responders.

Dr. Kolls and his team have developed a synthetic antibody that may neutralize the new coronavirus. The scientists tested the antibody in mice and are hopeful that it can work not just as prevention but also as a treatment for people who have already contracted the virus.

In their new study, which appears as a preprint on the server bioRxiv, Dr. Kolls and colleagues explain that the antibody works as a “decoy.”

Namely, one of the suspected reasons why the new coronavirus is so highly infectious is the fact that it binds more tightly than other similar viruses to a host cell receptor called angiotensin converting enzyme 2 (ACE2).

ACE2 is present on the surface of cells in the airways and the lungs, but it is also in tissue in the kidneys, liver, and gastrointestinal tract, which may explain why SARS-CoV-2 attacks all of these organs so readily.

The new protein that the team has developed is a decoy ACE2. To the virus, it looks like the real receptor, but it is not actually attached to healthy host cells.

The decoy protein serves as a distraction for the SARS-CoV-2 virus, intercepting before the virus attaches to the real ACE2 and causes infection.

In the next step, the scientists attached the decoy ACE2 to an antibody to help it live and move inside the body for longer.

“Unlike other agents in development against the virus, this protein is engineered to go to the lungs to neutralize the virus before it can infect lung cells,” explains Dr. Kolls.

Next, the researchers plan to test it in healthcare professionals and first responders because they are at a high risk of infection.

“Based on our data, we think it would work as an injection either once every 2 weeks or maybe even once a month.”

– Dr. Jay Kolls

For live updates on the latest developments regarding the novel coronavirus and COVID-19, click here.

Source: Read Full Article