• Natasha Breward

Vaccines and COVID-19: How the Pandemic is Influencing Vaccine Development

Updated: Oct 2, 2020

With everyone’s mind on COVID-19 and the race to develop a vaccine for this novel coronavirus, Pulse spoke with Delphine Davan, Director of Communications at IMV Inc., a Canadian pharmaceutical company working to develop a vaccine for COVID-19.

In order to understand what it takes to make a COVID-19 vaccine, it is important to know the steps needed to take a vaccine from initial testing to distribution. In normal circumstances, it takes years to develop a new vaccine which is what makes the COVID-19 vaccine so astounding; there are already numerous vaccine candidates in late-stage development despite the fact that the pandemic has been going on for less than a year. This truly exemplifies how the pandemic has transformed the healthcare and pharmaceutical industry.

Once a vaccine is manufactured, its first evaluation begins with pre-clinical assays in mice. These tests evaluate initial safety and efficacy of the vaccine. After initial safety and efficacy animal tests are conducted, further tests are done on bigger animals, such as ferrets, primates, or other species. In all pre-clinical studies, different cohorts are needed for different parameters, and a placebo group (a group that gets saline water instead of an active vaccine) is also required. Once there is enough animal safety and efficacy data, a clinical trial application (CTA) can be submitted to Health Canada. Health Canada will then evaluate the data and decide if the vaccine can enter human clinical trials, that usually start with “Phase 1”.

Phase 1 is used to evaluate the safety of the product and is done in a limited number (less than 100) of subjects. The participants in Phase 1 are healthy and have no other health conditions, as this stage is focused on evaluating the safety of the vaccine in healthy individuals. Subjects in Phase 1 may be monitored for over a year before the vaccine candidate can enter Phase 2. However, due to the urgency for a COVID-19 vaccine, researchers cannot wait for the end of Phase 1 to continue to Phase 2. Therefore, once preliminary Phase 1 data is obtained, usually around one-to-two months after the beginning of Phase 1, there is enough data to assess safety and efficacy and researchers can move on to Phase 2. For all COVID-19 vaccines, Health Canada and the US FDA required that subjects enrolled in Phase 1 are monitored for at least 12 months.

Phase 2 is used to evaluate the efficacy of the vaccine on a larger number (100s) of subjects. The timeline of Phase 2 depends on the number of volunteers recruited, and how long it takes to recruit the volunteers. For the COVID-19 vaccine, many people are stepping forward to volunteer for studies, and there is already a long list of volunteers for vaccine trials. While side effects will also be looked at in Phase 2, the main focus is to evaluate immune response.

Phase 3 is used to gain more data pertaining to efficacy and long-term safety. It usually takes years to get to Phase 3 and involves thousands of subjects in order to get more robust data and analysis of the impact of the vaccine. For the COVID-19 vaccine, as soon as first results of safety and efficacy are reported, companies can expand the number of volunteers from hundreds (Phase 2) to thousands (Phase 3). Long-term safety of the vaccine and potential side effects are evaluated. Participants that received the active vaccine are compared against the placebo group.

The efficacy of the vaccine in both Phase 2 and 3 is tested by assessing the immune response. The immune system is supposed to react and create antibodies after a vaccine is administered in order to prevent infection. Efficacy in human clinical trials is measured by assessing the neutralization of the virus by antibodies and the levels of different immune cells present in the body. Neutralization by antibodies is evaluated by extracting blood and looking at how antibodies bind and neutralize the virus in-vitro. If there is high neutralization of the virus by antibodies in-vitro, the vaccine is considered efficacious.

Like with every medication, benefits and risks need to be known and assessed, as the potential benefits need to outweigh the potential risks. IMV’s COVID-19 vaccine has the potential to show a good safety profile and side effects are expected to be limited to the site of injection as demonstrated in previous clinical studies with another vaccine of IMV. After each phase, Health Canada evaluates if the vaccine/medication is safe and effective for use.

Figure A: Pipeline of vaccine development.

After vaccine development, large scale manufacturing becomes the next challenge. The COVID-19 vaccine requires extremely large quantities to be manufactured as quickly as possible. The length of time required for manufacturing a vaccine depends on the vaccine type. There are vaccines that contain the inactivated virus, with the goal being that the immune system will react to this inactivated virus and create antibodies that will prevent future penetration of the virus. There are also DNA or RNA vaccines. Once these vaccines are injected, they will modulate a subject’s own cells, causing them to produce compounds that are fragments of the virus. The immune system will recognize these compounds and will create antibodies to them, therefore generating an immune response when exposed to the virus.

Another type of vaccine involves synthesizing different elements of the virus’ protein spike and injecting these elements to generate a specific immune response. IMV’s vaccine against COVID-19 is a formulation of these elements with its DPX platform, which has the potential to generate a targeted and sustained immune response. IMV's vaccine causes the production of antibodies that recognize the specific sequences of the protein spike with the potential ability to neutralize the virus (Figure B). IMV developed this type of vaccine by looking at four different peptide sequences in the virus’ spike that are not overlapping. By targeting these non-overlapping sequences, even if the virus mutates the vaccine is expected to continue to protect against the virus, as it is unlikely that all four targeted sequences will mutate at once. These vaccines are fully synthetic and can be manufactured quicker than vaccines dependent on biologic compounds (cells, yeast, etc.) for manufacturing, as biologic vaccines take more time to be developed and also require more evaluation for potential contamination.

Figure B: DPX-COVID-19 is designed to generate a specific immune response against SARS-CoV-2. (IMV Inc.)

There are challenges that come with creating a COVID-19 vaccine. The most prominent challenge is the need to produce the vaccine very quickly. The development of pharmaceuticals is usually a lengthy process, and regulatory agencies and manufacturers are unaccustomed to working at this speed. The development of a COVID-19 vaccine will surely change the way vaccines are produced in the future. Not only is the COVID-19 vaccine creating an amazing impact on the speed with which a vaccine can be produced, but it is also bringing together collaborations between different countries.

Another challenge comes with the lack of information about coronaviruses. They are most commonly associated with colds, and very little is known about them. Scientists were able to sequence the COVID-19 genetic information very quickly and at a very early stage, and this is how companies like IMV were able to identify peptide sequences to develop a vaccine. This may cause virus research to go even faster in the future and may lead to investigation of more viruses that can potentially cross the species barrier. With respect to the vaccine itself, if it unknown what the longevity of the immunization will be, and to what extent antibodies will protect people over time.

COVID-19 has had profound impacts on many aspects life, and the medical and pharmaceutical fields are no exception. Due to COVID-19, researchers are creating vaccines at previously unprecedented rates, which may lead not only to a COVID-19 vaccine, but also to more vaccinology research in the future.

(Title image provided by IMV Inc.).

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