By:CHRISTINA VARGA
Canadian researchers are part of the all-hands-on-deck global effort to develop a COVID-19 vaccine.
With several vaccine candidates on the go, part of the research effort is directed, not only at finding the right formula to stimulate a safe, effective immune response but also how to get the vaccine into the body in the most efficient way.
Although Pfizer Inc.’s announcement this week of an early indication of 90-per-cent effectiveness in its vaccine offers hope, it is important that vaccine researchers continue their work, experts say.
“The scientific community has come together to look at all options … to try to come up with the best solutions” for different situations, says Karina Top, an investigator at the Canadian Center for Vaccinology and an associate professor of pediatrics and community health and epidemiology at Dalhousie University. “So, casting that wide net is the best approach.”
There are many researchers working on injectable vaccines and nasal sprays, but in Canada a couple of projects are aimed at developing other delivery methods – a vaccine that can be inhaled and one that can be ingested.
SOME BASICS
There are many ways our bodies jump into action to defend us from harmful viruses, such as SARS-CoV-2, which causes COVID-19. In order to get a sense of the goals of research on COVID-19 vaccines, it’s helpful to know some basic facts about viral infection, the body’s defence mechanisms and how vaccines help.
“The purpose of any vaccine is to train the immune system to recognize a virus or bacteria that causes an infection, so when [you] encounter that infection, your immune system can fight it off before it can make you sick,” says Dr. Top.
When a virus enters the body, it has are certain defences, which include antibodies and T-cells.
Antibodies and antigens: One defence is the production of antibodies, which are proteins that latch onto antigens, or the molecules on foreign substances, such as the SARS-CoV-2 virus. Antibodies can recognize and inactivate specific antigens.
T cells: When viruses infect cells in the body, hijacking them to make more copies of themselves, killer T cells attack those infected cells. “The ideal vaccine would stimulate both arms of the immune system,” Dr. Top says.
Vaccines and spike proteins: In order for a vaccine to train the immune system to recognize and attack a virus, it needs to introduce to the body a safe version of the virus or parts of the virus or genetic instructions to make the virus. For instance, Dr. Top notes, many vaccine candidates target the spike proteins that stick out of the surface of the SARS-CoV-2 virus and attach themselves to our cells, which is how the virus invades cells and makes copies of itself.
Carriers: Antigens, such as spike protein, or instructions to make spike protein need to be introduced to the body through a carrier, which include a bacterium or another virus that will not harm the body.
Scientists also choose the method of administering the vaccine. The following research projects are developing methods that are more unusual:
AN INHALABLE VACCINE
Dr. Zhou Xing, a vaccine immunologist at McMaster University in Hamilton, is the lead scientist on a project focused on producing an inhaled aerosol vaccine.
The researchers on the project are developing two viral vector vaccines, which means the antigens, or molecules, they want the immune system to react to are delivered by viruses. One is a human adenovirus, a common virus that can cause such illnesses as the common cold or an intestinal illness. The other is an adenovirus derived from chimpanzees, which has the advantage of being new to the human body, so we do not already carry an immune response to it, potentially masking any responses to SARS-CoV-2 antigens.
Both are recombinant viral vector vaccines, meaning the delivery viruses are engineered to carry genetic instructions to cells in the body. These instructions guide the cells to produce the SARS-CoV-2 antigen targets for our immune systems to react to……………….
AN ORAL VACCINE
Imagine being able to take in pill form a COVID-19 vaccine at home. That is exactly what Symvivo – a clinical-stage gene therapy company founded in Burnaby, B.C., in 2013 – is working toward. The first volunteer for the project was dosed last week in a Phase 1 clinical trial underway in Australia.
“We have developed a novel way to deliver plasmid DNA to select sites in the body,” says Symvivo’s founder and chief executive officer, Alexander Graves.
Plasmid DNA is a small circle of DNA separate from the bacteria’s DNA that, in this case, has been manipulated to carry instructions for the body’s cells to produce SARS-CoV-2 spike proteins. Symvivo delivers the plasmid DNA through a modified bacterium.
“Bifidobacterium longum … is in everyone’s large intestine,” Mr. Graves points out. The company chose the method, he says, because it can effectively transit the gastrointestinal tract and deliver plasmid DNA to the lining of the large intestine.
“That spike protein, when expressed, will induce an immune response that, hopefully – and we are going to confirm this in the clinic – can provide protective immune responses against future SARS-CoV-2 infections.”
The product – bacTRL-Spike – can also be delivered intravenously, but there are several benefits to oral administration, Mr. Graves says.
One advantage is that the lining of the intestine, like that of the respiratory tract, is a mucous membrane routinely exposed to harmful substances and provides the first line of defence where antibodies are secreted.
This method allows the researchers to observe a mucosal response to SARS-CoV-2 antigens, Mr. Graves notes, and if people are exposed to the virus, they would already have antibodies at the lining of the mucosal membranes that would prevent the virus from entering the body.
An oral vaccine would also allow people to take it themselves without the need for needles and trained personnel.
“We are moving toward a room-temperature stable product,” he explains. This is an important factor when distributing the vaccine globally, as there would be no need to keep it cold – “a bottleneck that is current in the vaccine industry,” he says.
He adds that the bacterial product could make it easier to produce on a global scale because it could be manufactured with few changes to existing infrastructure.
Symvivo received $2.8-million in funding from the National Research Council of Canada Industrial Research Assistance Program. If Phase 1 trials prove that the bacTRL-Spike vaccine candidate is safe to use, the next step is to evaluate whether it stimulates an effective immune response to SARS-CoV-2. The aim is to move to Phase 2 trials in the new year.
“The ultimate goal is to produce a vaccine that we can send to people’s homes [and can be] self-administered,” Mr. Graves says. “And if there is a need for repeat vaccinations, that [can also be] enabled using this technology.”
Source: theglobeandmail.com
