Assessing the safety and effectiveness of current and future SARS-CoV-2 vaccines deployed in Canada


This call for proposals consists of a 2-step process that aims to expedite vaccine surveillance related research that has been deemed a public health priority


 

The Canadian Vaccine Surveillance Reference Group (VSRG), in partnership with the COVID-19 Immunity Task Force (CITF), and with the support of the Public Health Agency of Canada (PHAC), is inviting the Canadian research community to apply for funding to assess the safety and effectiveness of current and future SARS-CoV-2 vaccines deployed in Canada.

Two COVID-19 vaccines already approved by Canadian regulators are now in use. More are expected to be introduced in the months ahead. In this unprecedented situation with emergency approvals and rapid roll-out of new vaccines, there are many unanswered questions. The VSRG, drawing on colleagues from the National Advisory Committee on Immunization (NACI), the Canadian Immunization Research Network (CIRN), and the CITF, is prepared to fund research teams that can address major aspects of the safety and effectiveness of COVID-19 vaccines with public health relevance.

This Request for Applications (RFA) is for human studies (e.g., population-based, clinical cohorts, etc.) that will collect, analyze, and report novel data relating to SARS-CoV-2 vaccine effectiveness and safety. These data will help public health decision-makers understand vaccine responses in priority populations and can address specific issues that were not sufficiently elucidated in pre-licensure Phase 3 studies. Examples of populations that were understudied in clinical trials include:

  • Racialized communities
  • Indigenous communities
  • Individuals of lower socioeconomic status
  • Individuals with active co-morbidities
  • Individuals with primary or secondary immune defects
  • Individuals with cancer including those receiving treatments for their malignancies
  • Individuals with autoimmunity including those receiving treatments that may alter their immune response

Potential applicants should be mindful of existing federal and provincial public health infrastructures, as well as networks such as CIRN, (SIC, CANVAS, SOS, etc.) and studies funded by CIHR, CITF and other organizations. All proposals will be evaluated in the context of these ongoing studies. Other areas that have significant current investment in addition to the above networks include cohorts in pregnancy, individuals in congregate living settings (long-term care, shelters, correctional settings) as well as pediatric studies. Studies of SARS-CoV-2 variants, while crucial to these efforts, are the focus of an upcoming CIHR call for proposals.

This RFA is aimed at addressing important measures of vaccine safety and effectiveness and questions that require longitudinal study. Research teams are strongly encouraged to directly link with existing public health vaccine surveillance networks or infrastructures. Priority will also be given to applications that are multi-center and involve multiple provinces. Applicants may therefore wish to consider framing their submissions around the NACI priority questions outlined below:

Effectiveness

What is the population effectiveness of a complete series of a COVID-19 vaccine and is short, medium and long-term durations of protection?

What is the effectiveness of COVID-19 vaccines across specific population groups (e.g., adults of advanced age, those with high-risk medical conditions including autoimmune conditions and transplant recipients, individuals with social or occupational vulnerabilities, individuals who are pregnant or breastfeeding, children, frail adults)?

What is the effectiveness of COVID-19 vaccines in individuals who have had previous laboratory evidence of SARS-CoV-2 infection? Are there differences among those vaccinated following prior SARS-CoV-2 infection versus those who are SARS-CoV-2 naïve in terms of enhanced or altered disease upon subsequent infection by SARS-CoV-2 or by endemic coronaviruses?

What is the effectiveness of a single dose of a COVID-19 vaccine(s) authorized as a two-dose series? How long is the duration of protection for a single dose of a COVID-19 vaccine? Is there an optimal interval between the first and second dose of a COVID-19 vaccine?

Is one COVID-19 vaccine superior to another? What is the effect of different dosing intervals of the vaccines? If two doses of different COVID-19 vaccine products are used, what is the effectiveness and the immune response? What is the effectiveness of mixed schedules of vaccines from different manufacturers or platforms?

Can COVID-19 vaccination be used to protect household contacts of a case from infection? Does COVID-19 vaccination decrease infectiousness and clinical illness in individuals that have already acquired infection but are asymptomatic at the time of vaccination? Is COVID-19 vaccination effective in interrupting onward transmission?

Safety

What is the safety of COVID-19 vaccines across specific population groups (e.g., adults of advanced age, those with high-risk medical conditions including autoimmune conditions and transplant recipients, individuals with social or occupational vulnerabilities, individuals who are pregnant or breastfeeding, children, frail adults)?

What is the safety of COVID-19 vaccines in individuals who have had previous laboratory evidence of SARS-CoV-2 infection? Are there any emerging safety signals with COVID-19 immunization that are not predicted by the current understanding of the safety profile of similar mRNA vaccines?
Are some vaccines safer or more effective in certain sub-populations?

Are any components of COVID-19 vaccines more likely to induce an anaphylactic reaction?

What is the incidence of rare or serious adverse events following immunization with COVID-19 vaccines?

Are there any negative interactions between COVID-19 vaccination and medications for COVID or other diseases? What is the recommended timing between COVID-19 vaccines and anti-SARS-CoV-2 prophylactic or therapeutic monoclonal antibodies or convalescent plasma?

Immune response

What is the immunogenicity of COVID-19 vaccines across specific population groups (e.g., adults of advanced age, those with high-risk medical conditions including autoimmune conditions and transplant recipients, individuals with social or occupational vulnerabilities, individuals who are pregnant or breastfeeding, children, frail adults)?

Is SARS-CoV-2 natural infection (symptomatic or asymptomatic) associated with protection against reinfection or against severe disease if reinfection occurs? How are immune responses induced by natural infection similar or different from those induced by COVID-19 vaccines?

Further immunological evidence is needed in the following areas to inform effectiveness predictions:

  1. How do immune responses change over time and how durable are immune responses against SARS-CoV-2 over the long-term?
  2. Which immune responses are most important for protection from infection (adaptive or innate immunity), protection from severe disease, and prevention of onward transmission?
  3. Are immunoglobulin (IgA/IgG/IgM) antibodies protective against SARS-CoV-2 and what is the correlate of protection?
  4. Is there a cell-mediated immunity correlate of protection against SARS-CoV-2?

Does endemic coronavirus infection history influence the course of SARS-CoV-2 disease? Is there cross-protection or interference from antibodies/exposure to human seasonal coronaviruses when exposed to SARS-CoV-2 or vaccinated against SARS-CoV-2?

What is the immunogenicity of a single dose of a COVID-19 vaccine(s) authorized as a two-dose series? How long is the duration of protection for a single dose of a COVID-19 vaccine? Is there an optimal interval between the first and second dose of a COVID-19 vaccine?

General Questions

Other pertinent issues based on preliminary data provided by the applicants.


Application Process

This call for proposals is a fast-tracked two-step process:

Expression of Interest (EOI)

All potential applicants are required to fill out an EOI form which includes identification, priorities and a 2-page project description. EOIs will be reviewed and rated based on gaps that have been identified by the VSRG and alignment with the requirements of public health. EOIs will be accepted until February 15th, 2021 and projects that are prioritized will be immediately contacted to submit a full application.

Link to EOI form for Step 1

Adjudication

Full applications will be accepted continuously from the time an applicant is invited and will be sent for review upon submission on a rolling basis.

Full applications will be accepted until March 15th, 2021. Proposals will be submitted using application forms, provided by the CITF Secretariat upon invitation. All proposals will be peer reviewed by at least two experts, (one member of the VSRG Working Party and one outside expert). Applicants are requested to provide suggested reviewers at the time of submission. Applicants will receive feedback from the VSRG within 14 days of receipt of the proposal. Proposals may be i) deemed to be a priority for funding, ii) deemed to be low priority for funding, or iii) be returned for modification and reconsideration for funding.

Priority will be given to proposals that:

  • Include active participation by jurisdictional public health representatives.
  • Address more than one of the above research issues/questions.
  • Involve multiple centers, and in particular, multiple Canadian provinces/territories.
  • Build upon existing networks and surveillance capacity.
  • Include a plan for engaging with study populations/communities/patient groups.

As there may be more than one application addressing similar populations, teams may be recommended to join with other applicants to create a multicentre study if justified by feasibility, sample size, and budget.

Budget

Budgets must be commensurate with the scale and scope of study and be justified in the context of the resources required and other resources available to the investigator. We will consider studies up to a budget of $1.5M Canadian dollars. Exceptions may be made for very large collaborative studies.

The Public Health Agency of Canada does not provide institutional overhead but will consider amounts up to 18% of the grant’s total if an itemized account of the use of overhead is provided. Further details on request.

Data Sharing

Due to the need to rapidly communicate with Federal, Provincial, and Territorial Governments, all VSRG supported studies are required to comply with the following data sharing requirements:

  • Share interim results with the CITF Secretariat as rapidly as possible: on behalf of the VSRG, the CITF has a mandate to rapidly synthesize evidence about population immunity and report this information to decision makers. Accordingly, all PIs should report any initial results rapidly to the Secretariat. The CITF will not release these initial results publicly and will use them only for surveillance modelling and to inform policy briefs.
  • Share core data elements with the CITF Secretariat: To enable surveillance analysis and future research, all PIs should share with the CITF Secretariat their core data elements defined by the CITF. Resources are available to support PIs in ensuring that they meet all legal and ethical obligations required for sharing data with the CITF. Each PI and their organization will complete a data sharing agreement with the CITF, defining the responsibilities and obligations of each party in terms of data sharing.
  • Support documentation of their study: A description of all VSRG studies in a consistent format (e.g., population, variables collected, study design) is important to enable reporting about objectives, funding, and timelines with the greatest transparency. This catalogue of studies will also facilitate the development of research collaborations.

Equity, Diversity and Inclusion (EDI)

In alignment with the Government of Canada and national funding agencies, this RFA encourages EDI, in recognition that integration of EDI contributes to rigorous, relevant, and accessible research. Researchers may find the following links helpful in preparing their application.

Proposals are expected to:

Demonstrate active engagement from inception through to dissemination of the research of relevant public health partners and networks, in order to launch the study rapidly following approval;

Include a plan for engaging with study populations/communities/patient groups from study inception;

  • Consider a range of relevant independent variables that determine individual, racial, age, SES, and/or co-morbidity risks or protective factors;
  • Be innovative, interdisciplinary, and provide relevant timely information to inform public health decisions at the local/provincial/national levels;
  • Be carried out by March 31, 2022;
  • Be prepared to share anonymized aggregate data with the CITF in compliance with the CITF data sharing policy (see “Data sharing” above).

If the study includes measures of COVID-19 immunity (serological, cellular) it is highly recommended that applicants network with research teams already funded by the CITF. The CITF Secretariat will provide information as needed.


DATES OF IMPORTANCE

Event Dates
Launch of call for funding February 4, 2021
Submissions of Expression of Interest will be processed as they are received until… February 15th, 2021
Proposal preparation workshop February 25th, 2021
Submissions of full applications will be processed as they are received until… March 15, 2021
Feedback from VSRG Within approximately 14 days of receipt of proposals
If proposal changes are requested (i.e., revisions deadline) 7 days following return of proposal to investigators (if applicable)
Review of full proposal completed 7 -10 days after final proposal received (if applicable)
Funding announcements On a continuous basis until April 15 2021

Questions? proposals@covid19immunitytaskforce.ca