COVID-19 Vaccine Research and Development

23 June 2020, 2:15 p.m.

(Disponible en français : Recherche et développement de vaccins contre la COVID‑19)

Vaccine immunization will be a critical tool in controlling the spread of SARS-CoV-2, the virus that causes coronavirus disease (COVID-19). To date, more than 8 million cases of COVID-19 and more than 400,000 deaths have been reported worldwide. On 11 January 2020, the genetic sequence of SARS-COV-2 was published, allowing researchers to begin developing a vaccine. This HillNote provides an overview of COVID-19 vaccine research and development (R&D) along with efforts in Canada and globally to accelerate this process.

What is a Vaccine?

Vaccines are preventative medicines that help a person fight off infections of microorganisms such as bacteria and viruses. They work by using a person’s own immune system response to a modified infectious agent, or portion of it, which in turn conveys immunity against the native infectious virus or bacteria. A vaccine provides the antigen which provokes the immune system to produce antibodies against it.

Developing a Vaccine is a Long Process

The exploratory stage involves isolating and characterizing the infectious organism. This step requires purifying the organism and either selecting or making a version of it, or a portion of it, that will not cause disease but will still provoke the production of antibodies against the virulent strain. Viruses invade human cells by attaching to any one of a variety of receptors that are on our cells through protein molecules on the viral coat. These proteins, or the genetic sequence coding for them, can be identified and used in a vaccine. The portion of an infectious organism to which antibodies are produced is called the antigenic site. Antibodies against viral coat proteins will prevent the virus from infecting cells.

Next, potential antigens are tested for their ability to provoke an immune response (immunogenicity). This stage, called pre-clinical, can include testing in tissue cultures grown in laboratories and/or animal testing.

Once an appropriate immune response is detected, the candidate vaccine moves into three phases of human clinical trials to test its safety and efficacy (see Figure 1). Each clinical trial phase for a vaccine can still take several years or more to complete.

Figure 1: Clinical Trial Phases in Vaccine Research and Development

This infographic depicts the three different phases of the clinical trial process necessary for vaccine development and regulatory approval. During phase one, clinical trials are smaller, only involving dozens of volunteers. They do not include a placebo group. The purpose of this phase is to assess whether the vaccine is safe and whether the body produces antibodies in response to the vaccine. It also determines the optimal dosage of the vaccine. Phase two clinical trials usually last up to two years. During phase two, clinical trials involve hundreds of volunteers, who are placed into two different groups at random, with one group being given a placebo vaccine. Phase two clinical trials test safety, immunogenicity, route of delivery, dosage, and immunization schedule. Phase two clinical trials last between two and three years. Phase three clinical trials involve thousands of volunteers and can last between five and ten years on average. Volunteers are randomized into two groups with one group receiving the vaccine and the other receiving a placebo. Phase three clinical trials evaluate safety and efficacy in a large population groups and determine side effects in specific population groups. Once the clinical trial process is complete, the vaccine manufacturer creates a New Drug Submission based upon data from the trials and submits it to Health Canada for regulatory approval. The New Drug Submission is then approved by Health Canada, if it deems that the benefits of the vaccine candidate outweigh any risks.

Source: Prepared by the authors from The History of Vaccines, Vaccine Development, Testing and Regulation.

Finally, the antigen must also be successfully packaged into a solution that provokes the desired immune response, can be manufactured without too much difficulty and in sufficient quantities and is relatively stable.

Candidate vaccines can and do fail at any one of these stages. Only a small proportion of candidate vaccines are submitted for regulatory approval for use in Canada.

The Federal Government’s Role in Accelerating COVID-19 Vaccine Research and Development

Supporting rapid access to a COVID-19 vaccine is a critical part of the federal government’s pandemic preparedness and response plan. As part of a $1.1 billion National Medical Research Strategy to Fight COVID-19, the federal government is providing funding for the  R&D of COVID-19 vaccine candidates in Canada.

The University of Saskatchewan’s Vaccine and Infectious Disease Organization – International Vaccine Centre (VIDO-InterVac) and Medicago are two Canadian groups that have received federal funding to develop vaccine candidates and conduct clinical trials. The federal government has also provided funding to the National Research Council of Canada’s Human Health Therapeutics Research Centre to build its capacity to scale up production and testing of vaccine candidates for industrial production.

Health Canada’s Role

Once a vaccine has been developed, Health Canada is responsible for authorizing its use in Canada under the Food and Drugs Act. As part of its regulatory review, the department evaluates scientific and clinical evidence regarding the vaccine’s safety, quality and efficacy, which includes the results of clinical trials and the testing of vaccine lots produced by manufacturers.

However, the Minister of Health may expedite this review process under the Extraordinary Use New Drug (EUND) provisions of the Food and Drug Regulations. If there is an imminent public health risk, these provisions allow for the approval of a vaccine based upon results from animal studies and limited human clinical trial data.

However, drug manufacturers are still required to continue to monitor of the safety of the vaccine once it has been authorized for sale and report any adverse reactions to Health Canada. Alternatively, the Minister may expedite the approval of a vaccine candidate through an interim order issued under the Food and Drugs Act.

Intellectual Property

Vaccines are subject to intellectual property (IP) federal legislation. For example, patents may apply to the formulation of a vaccine, its manufacturing process, and its delivery mechanism. Trademarks may protect a brand associated with the vaccine, while copyright may protect its explanatory materials.

IP can support the development, manufacturing, and delivery of a vaccine by providing exclusive rights over the making and the use of a vaccine and its associated materials. Parties are more likely to invest in the costly R&D and manufacturing of a vaccine if they can leverage IP to recoup their investments and profit from their innovation. IP rights also provide means to direct other parties that manufacture and deliver the vaccine, and thus ensure quality control.

However, some stakeholders argue that IP may hinder the dissemination of a vaccine. IP rights (e.g. a patent) provide a limited monopoly over the supply of their subject matter (e.g. a patented invention). As a result, critics suggest that IP contributes to increasing the cost of vaccines. Moreover, because multiple parties may hold IP rights over a single vaccine, lack of coordination may lead to delays and obstacles in delivering it.

IP management may help overcome these challenges. Different IP holders may, for example, make “cross-licensing” arrangements allowing each party to use the others’ IP. Other actors, including governments, may ensure adequate dissemination through IP management, for example by requiring preferential or wide access to an IP-protected vaccine in exchange for funding.

Governments may also resort to compulsory licensing to allow the use of an IP-protected vaccine for non-commercial purposes without the permission of the IP holder, especially to ensure its delivery in less profitable markets or to respond to a national emergency.

Examples of such measures in patent legislation include Canada’s Access to Medicines Regime and provisions allowing the use of patents by the federal government. Compulsory licensing, however, has been used only sparingly in relation to pharmaceutical products, even in response to epidemics. Other mechanisms, such as Canada’s Patented Medicine Prices Review Board, may help increase accessibility to an IP-protected vaccine by regulating its price.

While IP arrangements for vaccines for SARS-CoV-2 are still being developed, some suggest that licensing arrangements should ensure that Canadians have priority access to federally funded vaccine candidates. The World Health Assembly recently supported IP arrangements that will facilitate global access to vaccines for SARS-CoV-2, including voluntary patent pooling initiatives.

Current Status of COVID-19 Vaccine Development

Work on developing a vaccine against SARS-CoV-2 is underway around the world. Work has progressed on over 100 candidate vaccines, using various approaches. Some companies, such as Sinovac and Codagenix, are pursuing the traditional whole virus approach (either inactivated or weakened) to vaccine development.

Others are deploying newer technologies to develop vaccines. For example, some companies are using protein subunits of the virus (University of Queensland, Novavax, Clover Biopharmaceuticals and Vaxart) or targeted portions of the virus’ genetic sequence (Inovio, Moderna and CureVac).

Vaccines developed using traditional techniques have a history of safe use, while innovative techniques such as genetic vaccines do not. As such, safety testing of innovative vaccines could require more regulatory stringency.

As of June 2020, the World Health Organization (WHO)’s Draft Landscape of COVID-19 candidate vaccines indicated that ten candidate vaccines have progressed to clinical evaluation, while the large majority remain at pre-clinical development stages. International collaboration through the WHO’s Solidarity Trial is expected to accelerate the clinical trial process for the most promising vaccine candidates. In addition, vaccine developers are also expediting this process by combining clinical trial phases.

On 15 April 2020, Health Canada granted authorization for the first clinical trials to be conducted for a vaccine candidate developed by China’s CanSino Biologics Inc. using cell line technology from the National Research Council of Canada. It is estimated that a vaccine could be available for EUND regulatory approval in Canada within the next 12 to 18 months.

However, it is still likely that despite these efforts, the first wave of COVID-19 will pass before a safe and effective vaccine is widely available.

Authors: Karin Phillips, Francis Lord and Sonya Norris, Library of Parliament

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