Mix and match of the second COVID-19 vaccine dose for SAfety and ImmunogeniCity

Coronaviruses are a large family of viruses found mostly in animals. In humans, they can cause diseases ranging from the common cold to more severe diseases such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS).  A new coronavirus was identified in an outbreak that began in Wuhan, China, in December 2019. The virus has been named SARS-CoV-2, and the infectious disease caused by the virus has been named COVID-19. The World Health Organization declared this virus as the cause of a pandemic in March 2020.

The most common symptoms of COVID-19 are fever, tiredness, and dry cough. Some patients may have aches and pains, nasal congestion, sore throat or diarrhea. These symptoms are usually mild, and most people recover from the disease without needing special treatment. However, people over age 60, or those with weakened immune systems, or underlying medical problems have a higher risk of developing serious complications or dying from COVID-19. Researchers around the world are studying the virus and its effects, and working on ways to fight it, including vaccines.

Vaccines are one way to protect against disease. Vaccines work by preparing the immune system, the system in your body that fights disease, to react quickly against germs, such as viruses or bacteria, should they ever enter the body in the future. Vaccines trigger the body’s defenses to produce disease-fighting antibodies. If a germ enters the body, the immune system will be prepared for it. The immune system will be able to destroy the germ before it can do harm.

A mRNA vaccine teaches our cells how to make a protein that will trigger an immune response. It does not use the live virus that causes COVID-19. When our body see the protein it then makes antibodies. These antibodies help us fight the infection if the real virus does enter our body in the future.

‘RNA’ stands for ribonucleic acid, which is a molecule our cells use to provide instructions for making proteins. Messenger RNA (mRNA) vaccines contain the genetic instructions for making the SARS-CoV-2 spike protein, which is found on the surface of the virus that causes COVID-19.

When a person is given the vaccine, their cells will read the genetic instructions like a recipe and produce the spike protein. After the protein piece is made, the cell breaks down the instructions and gets rid of them.  The cell then displays the protein piece on its surface. Our immune system recognizes that the protein doesn’t belong there and begins building an immune response and making antibodies.

A vector-based vaccine uses a virus, such as an adenovirus, as a delivery system. This “vector” virus is not the virus that causes COVID-19. Adenoviruses are among the viruses that can cause the common cold.  When a person is given the vaccine, the vector virus contained within the vaccine helps our cells produce the SARS-CoV-2 spike protein. This protein is found on the surface of the virus that causes COVID-19. Our immune system recognizes that the protein doesn’t belong there and begins building an immune response and making antibodies.

The AstraZeneca vaccine was used in public health immunization programs in Canada, but some provinces stopped using this vaccine. A second adenovirus virus vectored-based vaccine (Janssen Inc.) is approved but has not yet been used in public health programs in Canada. 

It was difficult for companies to make enough vaccines for all the people who needed them in the world. The interruptions to vaccine supply in the face of large outbreaks led some provinces to use a strategy to deliver as many first vaccines doses as possible. Other provinces or territories initially held back the second dose in order to deliver it according to schedule to recipients of the first dose. This resulted in mixed vaccine brands and schedules being used.

Data has shown the effectiveness of all vaccines against severe outcomes up to 6 months after vaccine however, there is some evidence of decreasing antibody levels in some populations (e.g. persons with weak immune systems) and of effectiveness. There are currently recommendations from the from the US – Centre for Disease Control (CDC) and in Canada by the National Advisory Committee on Immunization (NACI) for a third booster dose in certain populations.


An initial part of this MOSAIC study was commenced to compare the effectiveness, safety and acceptability of different dosing schedules of the first two doses of COVID-19 vaccines. That study began in June 2021 and is ongoing at 7 clinical sites in Canada where 195 participants were enrolled and received either both of their vaccines or the second authorized COVID-19 vaccine. Assessment of the safety, tolerability and immune response in these participants is ongoing.


This study will be conducted at 7 clinical sites in Canada. The study will evaluate the safety, tolerability and immune response to a third dose of a COVID-19 vaccine currently authorized in Canada (either the Pfizer-BIONTech or Moderna mRNA vaccine) in persons who received both doses of their first COVID-19 vaccines at least 6 (six) months ago.

This study will look at:

  1. What the effectiveness and length of immune response (protection) is after receiving different COVID vaccine products for the first 2 doses?
  2. What is the safety and effectiveness if different COVID-19 vaccine products are used for the 3rd dose?

How will the researchers do the study?

About 800 participants will take part in this study at 7 sites in Canada. Approximately 84 will take part at the Research Support Unit in Winnipeg.

The study involves providing a third dose COVID-19 vaccine of either the Pfizer-BioNTech and Moderna vaccine.

All the vaccines used in this study are authorized for use in public health programs in Canada during the COVID-19 pandemic.

This is a participant-blinded study. You will not be able to choose which vaccine you receive.  It is important to stay blinded until at least 28 days after the vaccine dose. You will only be told which vaccine you received at the end of study. If there is an emergency, or if it required for documentation due to public health measures or employment, we will record the date you saw which vaccine you received. This way, the results from the different groups will be handled in the same way. 

This is a randomized study.  Randomized means that your vaccine group will be chosen at random (like rolling a dice). You have an equal chance of being placed in each group. 

There are 8 study groups (see Table). Your 3rd dose of COVID-19 vaccine will be determined based on which vaccines you received for dose 1 & 2 prior to this study.

Study Groups

GroupVaccine Dose 1Vaccine Dose 2 Study Vaccine Dose 3
1bPfizer/BioNTech mRNAPfizer/BioNTech mRNAPfizer/BioNTech mRNA
2bPfizer/BioNTech mRNAPfizer/BioNTech mRNAModerna mRNA
3bModerna mRNA Moderna mRNAModerna mRNA
4bModerna mRNAModerna mRNAPfizer/BioNTech mRNA
5b  Moderna mRNA or Pfizer/BioNTech mRNA1  Moderna mRNA or Pfizer/BioNTech mRNA1Moderna mRNA
6b  Moderna mRNA or Pfizer/BioNTech mRNA1  Moderna mRNA or Pfizer/BioNTech mRNA1Pfizer/BioNTech mRNA
7bAstraZenecaPfizer/BioNTech mRNA or Moderna mRNA2Pfizer/BioNTech mRNA
8bAstraZeneca Moderna mRNA or Pfizer/BioNTech2Moderna mRNA

1 In group 5 and 6 the first and second dose can be either mRNA vaccine as long as they are not the same for both doses.

2 In groups 7 and 8 the second dose can be either mRNA vaccine.

You can take part in this study if:

  1. You are between 30 years of age and older
  2. You are available for all the study visits.
  3. You are in good health with stable health conditions.
  4. You are not pregnant.
  5. You have a record of first two doses of the authorized COVID-19 vaccines you received.

There are other study criteria that will be reviewed at the first visit to determine if you are eligible or not.

What will I be asked to do?

You will have 4 clinic visits and 1 telephone/email contact during a 12-month period.  The total time commitment is approximately 2-3 hours. If you are enrolled in MOSAIC-1, you will not be scheduled for any more MOSIAC-1 study visits and instead have MOSIAC-2 study visits only.

Will the study cost me anything, and, if so, how will I be reimbursed?

There are no costs to you to be in the study. The sponsor will obtain the study vaccine from public health and pay for tests that are part of the study.

As reimbursement for out-of-pocket expenses such as travel costs to and from study visits, you will receive $50.00 as well as up to $7.00 for parking.

Primary Investigators

Dr. Sergio Fanella- Local Investigator

Dr. Serigio Fanella is an Associate Professor, Diseases Pediatric Infectious Diseases at the University of Manitoba. He is also the Pediatric Infectious Diseases Residency Program Director of Pediatrics and Child Health at the University of Manitoba.

Dr. Joanne Langley- National Investigator 
Dr. Joanne Langley is a Professor of Pediatrics and Community Health and Epidemiology at Dalhousie University and the Canadian Center for Vaccinology in Halifax, NS Canada, head of Pediatric Infectious Diseases at the IWK Health Centre, and lead for the Clinical Trials Network of the Canadian Immunization Research Network. She currently co-chairs the Canadian COVID-19 Vaccine Task Force. Her research is focused on the epidemiology and vaccine prevention of respiratory infections, particularly Respiratory Syncytial Virus and influenza, and immunization decision-making.

Dr. Guillaume Poliquin, Acting Vice President, National Microbiology Laboratory- Local Investigator 
Dr. Poliquin completed his medical degree at Western University prior to pursuing a pediatrics residency at the University of Manitoba, followed by a fellowship in pediatric infectious diseases also at the University of Manitoba. After residency, Dr. Poliquin joined the Public Health Agency of Canada’s National Microbiology Laboratory’s (NML) Special Pathogens Division for a Ph.D. focused on Ebola virus. He has since assumed the role of Medical Advisor to the Scientific Director General at the NML, and is now acting Vice President. These roles are rounded out with a pediatric infectious diseases consultative practice in Winnipeg, as well as general pediatrics practice in remote communities in northern Manitoba and Nunavut. Dr. Poliquin’s research portfolio is primarily focused on vaccine research and emerging pathogens, such as Ebola and, more recently, SARS-CoV-2.

Dr Guillaume Poliquin, vice-président par intérim du Laboratoire national de microbiologie
Le Dr Poliquin détient un diplôme en médecine de l’Université Western. Il a effectué sa résidence en pédiatrie à l’Université du Manitoba et a ensuite obtenu une bourse de recherche en maladies infectieuses pédiatriques, également de l’Université du Manitoba. Après sa résidence, le Dr Poliquin s’est joint à la Division des agents pathogènes spéciaux du Laboratoire national de microbiologie (LNM) de l’Agence de la santé publique du Canada pour rédiger sa thèse de doctorat sur la maladie à virus Ebola. Il a assumé le rôle de conseiller médical auprès du directeur général scientifique du LNM, et occupe désormais le poste de vice-président par intérim. Outre ces fonctions, le DPoliquin est consultant en maladies infectieuses pédiatriques à Winnipeg et pratique la pédiatrie générale dans les communautés éloignées dans le nord du Manitoba et au Nunavut. Le portefeuille de recherche du DPoliquin porte principalement sur les vaccins et les agents pathogènes émergents, comme le virus Ebola et, plus récemment, le SARS-CoV-2.

Dr. Manish Sadarangani- National Investigator
Dr. Manish Sadarangani is Director of the Vaccine Evaluation Center at the BC Children’s Hospital Research Institute and an Associate Professor in the Division of Infectious Diseases, UBC Department of Pediatrics.


How to Participate

Please contact our study site coordinator directly to learn how you can get involved. 

Email: or phone: 204-789-3206


Partners and Sponsors

Canadian Immunization Research Network

The Canadian Immunization Research Network (CIRN) is a national network of key vaccine researchers who develop, and test methodologies related to the evaluation of vaccines as they pertain to safety, immunogenicity and effectiveness, and program implementation and evaluation. CIRN’s objective is to further strengthen Canada’s research capacity, evidence base and expertise in the field of immunization and vaccines for vaccine-preventable diseases. A ‘network or networks’, CIRN plays a pivotal role in mentoring early-career researchers, recruiting new investigators, providing opportunities for trainees, and delivering meaningful engagement of stakeholders at all research stages.
CIRN is made up of the following 8 networks: the Canadian National Vaccine Safety Network (CANVAS); the Clinical Trials Network (CTN); the Serious Outcomes Surveillance Network (SOS); the Special Immunization Clinic Network (SIC); the Provincial Collaborative Network (PCN); the Social Sciences and Humanities Network (SSHN); the Modeling and Economics Research Network (ModERN); and the Reference Laboratory Network (RLN).

Dalhousie University

Dalhousie University is Atlantic Canada’s leading research-intensive university. Located in the heart of Halifax, Nova Scotia, with an Agricultural Campus in Truro/Bible Hill, Dalhousie is a truly national and international university, with more than half of the university’s 20,000-plus students coming from outside the province. Dal’s 6,000 faculty and staff foster a diverse, purpose-driven community, one that spans 13 faculties and conducts more than $181 million in research annually. Part of a cluster identified as one of the world’s top international centers in ocean research, the university proudly celebrated its 200th anniversary in 2018.

Vaccine Surveillance Reference Group

The Vaccine Surveillance Reference Group (VSRG) supports the monitoring of the safety and effectiveness of COVID-19 vaccines in Canada. It is a consortium of Canadian organizations – the Public Health Agency of Canada (PHAC), the Canadian Research Immunization Network (CIRN), the National Advisory Committee on Immunization (NACI) and the COVID-19 Immunity Task Force (CITF) – working collaboratively to pool expertise on vaccine surveillance. The VSRG reports to the President of the Public Health Agency of Canada (PHAC) and is supported by the COVID-19 Immunity Task Force (CITF) Secretariat. It is co-chaired by the leaders of the National Advisory Committee on Immunization (NACI) and the Canadian Immunization Research Network (CIRN). Among its responsibilities, the VSRG, through the CITF Executive Committee, makes recommendations to PHAC on funding research teams that can address important aspects of the immune response, safety, and effectiveness of COVID-19 vaccines with public health relevance and with attention to all priority groups.

Learn more 

COVID Immunity Task Force (CITF)

In late April 2020, the Government of Canada established the COVID-19 Immunity Task Force with a two-year mandate. The Task Force is overseen by a Leadership Group of volunteers that includes leading Canadian scientists and experts from universities and healthcare facilities across Canada who are focused on understanding the nature of immunity arising from the novel coronavirus that causes COVID-19. To that end, the CITF is supporting numerous studies to determine the extent of SARS-CoV-2 infection in Canada (in the general population as well as in specific communities and priority populations), understand the nature of immunity following infection, develop improved antibody testing methods, and help monitor the effectiveness and safety of vaccines as they are rolled out across Canada. The Task Force and its Secretariat accordingly work closely with a range of partners, including governments, public health agencies, institutions, health organizations, research teams, other task forces, and engages communities and stakeholders. Most recently, the Task Force has been asked to support vaccine surveillance, effectiveness and safety as part of its overall objective to generate data and ideas that inform interventions aimed at slowing – and ultimately stopping – the spread of SARS-CoV-2 in Canada.

Learn more