Question Period Note: NACI’s recommendations on the use of COVID-19 vaccines

• What are NACI’s updated recommendations on COVID-19 vaccines?

KEY MESSAGES
• Canada’s National Advisory Committee on Immunization (NACI) has updated its recommendations on COVID-19 vaccines based on the latest scientific evidence.
• NACI reinforced its recommendations supporting the use of mRNA vaccines.
• mRNA vaccines are considered interchangeable, so Pfizer and Moderna can be used together in a two-dose series.
• An mRNA vaccine is preferred as the second dose for individuals who received a first dose of AstraZeneca/COVISHIELD vaccine.
• Provinces and territories have already begun to adjust their immunization programs.
• COVID-19 vaccines, authorized for use in Canada, are saving lives and are essential to ending the pandemic.
• Canada’s vaccine rollout continues to accelerate, and we remain on track to fully vaccinate everyone who wants to receive a vaccine by this September.

IF PRESSED on whether mRNA vaccines are preferred over the Janssen and AstraZeneca viral vector vaccines:
• Health Canada has determined that the benefits outweigh the risks of all vaccines used in Canada. The strict regulatory requirements for safety and efficacy have been met as the basis for authorization of COVID-19 vaccines for use in Canada.
• Vaccine safety and effectiveness monitoring is built into vaccine rollout so that any safety signals are detected and acted on immediately.
• I encourage Canadians to have confidence in the immunization programs offered in their province or territory.
• If you received a COVID-19 vaccine, you made the right choice. You chose to protect yourself, your family and your community from COVID-19.

IF PRESSED on interchangeability of COVID-19 vaccines:

• Updated recommendations are based on current evidence and NACI expert opinion. Recent studies from Germany suggest a potentially better immune response produced by a mixed COVID-19 vaccine schedule.
• People who received two doses of AstraZeneca vaccine can rest assured that the vaccine provides good protection against infection and very good protection against severe disease and hospitalization.
• NACI continues to closely monitor the evolving evidence and will update recommendations as needed.

BACKGROUND
Canada’s National Advisory Committee on Immunization (NACI) is an external body of experts in the fields of pediatrics, infectious diseases, immunology, pharmacy, nursing, epidemiology, pharmacoeconomics, social sciences and public health, which provides independent advice to the Public Health Agency of Canada (PHAC) on the optimal use of vaccines in Canada.

NACI is providing Recommendations on the Use of COVID-19 Vaccine(s) to help inform the ethical, equitable and effective rollout of COVID-19 vaccines in the context of staggered authorization and supply of vaccines.

As regulator, Health Canada rigorously evaluates safety and efficacy data from clinical trials before authorizing vaccines, but does not dictate practice of medicine or make recommendations on how the vaccines should be used in different age groups and sub-populations for public health impact.
When developing its recommendations, NACI assesses how best to use an authorized vaccine to achieve the greatest public health benefits. It analyzes the spread of COVID-19 in Canada and the risks for population subgroups; applies real-world data on the safety and effectiveness of COVID-19 vaccines; and develops advice on the equitable use of vaccines given vaccine supply. NACI may make recommendations that are broader or narrower than the conditions of use approved by the regulator. NACI also reviews evidence as it evolves, which is why recommendations may change.
NACI’s guidance is advisory in nature, as immunization program planning and delivery decisions fall under provincial and territorial responsibilities. Provincial and territorial governments will ultimately consider their unique needs and circumstances when planning and implementing immunization programs.
NACI Recommendations on the use of COVID-19 vaccines
Since the authorization of the first COVID-19 vaccine in Canada in December 2020, NACI has been providing recommendations to help inform the ethical, equitable and effective rollout of COVID-19 vaccines in the context of staggered authorization of vaccines. To date, NACI has published recommendations on the use of the Pfizer-BioNTech, Moderna, AstraZeneca, and Janssen COVID-19 vaccines, as well as guidance on subjects such as extended dose intervals and the interchangeability of vaccines.

There have been confirmed cases of rare but serious blood clots with low levels of blood platelets after receipt of the AstraZeneca and Janssen vaccines, a condition referred to as Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT). NACI has weighed the benefits of the AstraZeneca and Janssen vaccines in saving lives and protecting populations against serious complications of COVID-19 against the risk of developing VITT. Healthcare professionals should be aware of VITT, including how to diagnose and treat the condition. Individuals who receive the AstraZeneca or Janssen COVID-19 vaccine should monitor their health and immediately seek medical attention if they develop symptoms of VITT.

In early clinical trials, individuals who were immunosuppressed due to disease or treatment, have an autoimmune condition, are pregnant or are breastfeeding, were either excluded from or were represented by small numbers of participants. Based on this limited clinical trial data, NACI recommended that authorized COVID-19 vaccines may be offered to individuals in these populations in some circumstances, on a case-by-case basis, if the benefits outweighed the risks.
Additional evidence is now available from international real world use of COVID-19 vaccines, primarily mRNA vaccines, in these populations. In May 2021, NACI reviewed vaccine safety data, as well as COVID-19 risks for these groups. Evidence showed COVID-19 vaccines are safe and effective in these populations. As such, NACI recommendations for these populations are now the same as recommendations for the general adult population.
Current Recommendations

NACI released updated recommendations on June 17, 2021. NACI continues to preferentially recommend a complete series with an mRNA COVID-19 vaccine should be offered to individuals in the authorized age group, including those who are immunosuppressed, have an autoimmune disease, are pregnant or are breastfeeding, without contraindications to the vaccine. If an mRNA vaccine is contraindicated, another authorized COVID-19 vaccine should be offered. NACI preferentially recommends mRNA vaccines due to the excellent protection they provide and the absence of the VITT safety signal.
NACI recommends a viral vector COVID-19 vaccine may be offered to individuals in the authorized age group for a first dose when an mRNA vaccine is inaccessible or contraindicated.
In making this recommendation, NACI considered the recent epidemiology of COVID-19 in Canada, including the circulation of variants of concern; evidence on VITT, including risk and rates associated with viral vector vaccines but not associated with the mRNA vaccines; Canada’s increasing supply of mRNA vaccines; and a comprehensive analysis of the implications on ethics, equity, feasibility, and acceptability.
NACI recommends that COVID-19 vaccines should not routinely be given at the same time as other vaccines. If possible, COVID-19 vaccines should be given at least 14 days after and 28 days before other vaccines to avoid possible overlapping side effects and potential (but unknown) interference with the immune response between vaccines.
There may be circumstances when a dose of a COVID-19 vaccine and a non-COVID-19 vaccine need to be administered at the same time or when a non-COVID-19 vaccine needs to be administered within 28 days after a COVID-19 vaccine. Examples include when a non-COVID-19 vaccine is needed after an exposure to another infectious disease or when an individual is about to start a treatment that will weaken their immune system.
A healthcare professional can help to make this assessment and can discuss the benefits and possible risks with the individual.
NACI continues to recommend that a complete series with the Pfizer-BioNTech COVID-19 vaccine should be offered to adolescents 12 to 18 years of age.
At this time, NACI continues to recommend that people previously infected with the SARS-CoV-2 virus be offered a complete series of a COVID-19 vaccine.
Rare cases of myocarditis and pericarditis following vaccination with mRNA COVID-19 vaccines have been reported in Canada and internationally, including in Israel and the United States. Most international cases have occurred after a second dose of an mRNA vaccine in males 16 to 30 years of age. Cases have generally been mild and resolved with medical treatment. There is no data yet on myocarditis/pericarditis using a mixed vaccine schedule.

No clear association between myocarditis/pericarditis and mRNA COVID-19 vaccines has been established in Canada and no regulatory action has been taken in Canada or internationally. This may change as more evidence emerges and as Canada administers more second doses of mRNA vaccines.

NACI continues to closely monitor the evolving data on authorized COVID-19 vaccines and update their recommendations as needed.

Extended intervals
In February 2021, the Public Health Agency of Canada and the Chief Medical Officers of Health from across the country asked NACI to revisit their dose interval recommendation, given new real-world evidence of the protection of one dose of COVID-19 vaccines and the need for jurisdictions to implement vaccine intervals beyond six weeks.
In response to this request, NACI thoroughly reviewed all available evidence regarding efficacy (clinical trials), effectiveness (real-world use) and duration of protection of the first dose of COVID-19 vaccines, including in sub-populations (e.g., older adults). NACI also assessed the impact of extending the interval between the priming (first) dose and boosting (second) dose on the immune response; the impact of extended dose intervals on variants of concern; and the population-level impacts of rapidly providing more people with a first dose of a COVID-19 vaccine.
On March 3, 2021, NACI released a rapid response recommending that in the context of limited vaccine supply and ongoing pandemic disease, jurisdictions should maximize the number of individuals benefiting from the first dose of an effective COVID-19 vaccine by extending dose intervals of all authorized two-dose COVID-19 vaccines up to four months. Due to the urgency for jurisdictions to consider implementing extended dose intervals, the rapid response statement contained an abridged rationale. On April 7, 2021, the full advisory committee statement explaining NACI’s rationale for the recommendation, including updated detailed evidence summaries and references, was published. NACI’s recommendations have not changed since the March 3 Rapid Response publication.

In May 2021, NACI reviewed up to date information on vaccine effectiveness from Canada and the United Kingdom, where extended intervals are also being used. Evidence continues to suggest good protection against COVID-19 symptomatic infection, hospitalization and death following one dose of all COVID-19 vaccines authorized for use in Canada. A second dose is still required to provide optimal and longer-lasting protection.
NACI continues to recommend jurisdictions maximize the number of individuals benefiting from the first dose of a COVID-19 vaccine by extending dose intervals of all authorized two-dose COVID-19 vaccines up to four months. At this stage in the pandemic, and with Canada’s increasing vaccine supply, second doses should be offered as soon as possible with priority given to those at highest risk of severe illness and death after or at the same time as first doses are offered to all remaining eligible populations.
The extended dose interval recommendation is based on:
• Clinical trial evidence that demonstrates very good vaccine efficacy from the first dose;
• New real-world evidence that suggests good vaccine effectiveness against symptomatic disease and asymptomatic infection and very good effectiveness against hospitalization, including among older populations (there is currently no evidence that this protection decreases over time);
• Mathematical modelling, which demonstrates that accelerating vaccine coverage by extending dose intervals would have substantial population-level benefits by reducing symptomatic disease, hospitalizations and deaths while there is limited vaccine supply;
• Knowledge of vaccines, which indicate that a longer interval between the first and second dose generally results in a better immune response after the second dose;
• Experience with other multi-dose vaccines, which suggests that protection from first dose of a vaccine series can last six months or longer, while second doses extend protection even longer;
• Public health principles of ethical decision-making, including equity, feasibility and accessibility, which favour extending intervals, especially while cases of COVID-19, hospitalizations, and severe illness and deaths, are high, and faster progress towards population protection will help to protect vulnerable populations; and
• NACI’s expert opinion that within a global pandemic setting, reducing the risk of severe disease outcomes in the majority of the population and decreasing transmission in the community will have the greatest public health impact.

The impact of extending the interval between doses on variants of concern is unknown; however, there is currently no evidence that an extended interval between doses will either increase or decrease the emergence of variants of concern. COVID-19 mRNA vaccines and the AstraZeneca vaccine have shown promising early results against variant B.1.1.7, first detected in the United Kingdom. As effectiveness of the first dose against other variants of concern is emerging, ongoing monitoring will be conducted.

NACI will continue to closely monitor the evidence on effectiveness of extending dose intervals, including on variants of concern, and will update its recommendations as needed.

Vaccine Interchangeability

On June 1, 2021, NACI released a rapid response statement with recommendations on the interchangeability of authorized COVID-19 vaccines. These recommendations were urgently needed for provinces and territories to consider as they plan the rollout of second doses.

Recommendations were based on up to date evidence and NACI’s expert opinion. Recent studies on the safety of and immune responses produced by mixed COVID-19 vaccine schedules provided the evidence for vaccine interchangeability. A study from Germany and the CoM-CoV clinical trial from the United Kingdom report on the safety of mixed schedules, and the Spanish CombiVacS trial reports on both the safety and immune responses produced from mixed COVID-19 vaccines.

Current evidence suggests a first dose of the AstraZeneca vaccine followed by a second dose of an mRNA vaccine (Pfizer-BioNTech was used in studies) has a good safety profile at shorter (4 week) and longer (8 to 12 week) intervals. NACI also considered the risk of VITT associated with the AstraZeneca/COVISHIELD vaccine, Canada’s current and projected mRNA vaccine supply and principles of ethical decision-making.

On June 17, 2021, NACI released updated recommendations on mixed vaccine schedules based on emerging evidence of a potentially better immune response produced by a mixed vaccine schedule.
NACI continues to recommend that the same mRNA vaccine administered for the first dose should be offered for the second dose. If the same mRNA vaccine is not readily available, or the vaccine administered for the first dose is unknown, another mRNA vaccine can be considered interchangeable and should be offered to complete the vaccine series.
An mRNA vaccine is now preferred as the second dose for individuals who received a first dose of the AstraZeneca/COVISHIELD vaccine. Results from recent German studies suggest a potentially better immune response, including against variants of concern, when a first dose of the AstraZeneca vaccine is followed by a second dose of the Pfizer-BioNTech vaccine compared to two doses of the AstraZeneca vaccine. Evidence continues to suggest a mixed vaccine schedule has a good safety profile. Receiving an mRNA vaccine as a second dose also mitigates the potential risk of VITT associated with viral vector vaccines.
Provinces and territories will determine the best way to manage their vaccine supply.
NACI continues to closely monitor the evolving evidence and will update recommendations as needed.
COVISHIELD
NACI has not conducted (nor have they been asked to conduct) an external review of the COVISHIELD vaccine, Serum Institute of India (SII) version of the AstraZeneca COVID-19 vaccine. As such, NACI’s updated recommendations do not include recommendations on the use of the SII COVID-19 vaccine; however, Health Canada has determined the AstraZeneca and SII COVID-19 vaccines are comparable.
Indigenous Communities
The Government of Canada continues to engage Indigenous leaders on planning for vaccine programs, and to determine how to best serve Indigenous peoples, many of whom live in crowded multi-generational housing. Given the particular challenges some of these communities face, special consideration will be given to vaccine rollout in these communities.

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