# Preamble
The National Advisory Committee on Immunization (NACI) is an External Advisory Body that provides the Public Health Agency of Canada (PHAC) with independent, ongoing and timely medical, scientific, and public health advice in response to questions from PHAC relating to immunization.
In addition to burden of disease and vaccine characteristics, PHAC has expanded the mandate of NACI to include the systematic consideration of programmatic factors in developing evidence based recommendations to facilitate timely decision-making for publicly funded vaccine programs at provincial and territorial levels.
The additional factors to be systematically considered by NACI include: economics, ethics, equity, feasibility, and acceptability. Not all NACI statements will require in-depth analyses of all programmatic factors. While systematic consideration of programmatic factors will be conducted using evidence-informed tools to identify distinct issues that could impact decision -making for recommendation development, only distinct issues identified as being specific to the vaccine or vaccine-preventable disease will be included.
This statement contains NACI's independent advice and recommendations, which are based upon the best current available scientific knowledge. This document is being disseminated for information purposes. People administering the vaccine should also be aware of the contents of the relevant product monograph. Recommendations for use and other information set out herein may differ from that set out in the product monographs of the Canadian manufacturers of the vaccines. Manufacturer(s) have sought approval of the vaccines and provided evidence as to its safety and efficacy only when it is used in accordance with the product mono graphs. NACI members and liaison members conduct themselves within the context of PHAC's Policy on Conflict of Interest, including yearly declaration of potential conflict of interest. August 19, 2022, as a booster dose in children 5 to 11 years of age. This is the first COVID-19 vaccine authorized as a booster dose in this age group.  A COVID-19 wave driven by the BA.5 and BA.4 Omicron sub-lineages is underway, with increasing rates of hospitalizations and deaths being observed since early summer (1) .  As of July 17, 2022, 42% of the population aged 5 to 11 years of age in Canada is vaccinated with a primary series. Hybrid immunity (i.e., protection due to a combination of both infection and appropriate vaccination) has increased as many Canadians, particularly young Canadians, have now been infected with SARS-CoV-2.  Although to date Omicron variants have generally been associated with a less severe illness compared to previous strains, Omicron is partially evasive of immunity conferred by ancestral COVID-19 vaccines or a previous infection by pre-Omicron strains. Emerging data on BA.4 or BA.5 also suggests some degree of immune evasion against antibodies triggered by a previous Omicron BA.1 infection (2)(3)(4) .  Preliminary evidence in adults suggests infection-and/or vaccine-acquired immunity wanes over time, including protection against severe disease. This supports administration of subsequent vaccine doses (especially in groups at high risk of severe disease and/or waning) to improve protection in case of increases in COVID-19 indicators (e.g., case incidence, test positivity, outbreaks, wastewater signals).  Manufacturers are working on new COVID-19 vaccines, including multivalent vaccines and vaccines specifically targeting VOCs, including Omicron variants. A bivalent vaccine, containing the ancestral strain and Omicron BA.1 strain, is anticipated to be available for use in adults in the coming months, and trials in the pediatric population are in progress.
NACI continues to recommend a primary series with an authorized mRNA vaccine in all age groups 5 years of age, and a booster dose for those who are eligible. Immunization of those who are eligible for vaccination but have not yet received a primary vaccine series continues to remain a top priority in Canada. For children 6 months to 5 years of age, NACI recommends that a complete series with the Moderna Spikevax (25 mcg) COVID-19 vaccine may be offered at this time.
NACI continues to monitor the rapidly evolving scientific data recognizing that the trajectory of the COVID-19 pandemic remains unclear. Updated recommendations will be made as needed.
NACI's recommendations remain aligned with the goals of the Canadian COVID-19 Pandemic Response that have been updated on February 14, 2022:
- To minimize serious illness and death while minimizing societal disruption as a result of the COVID-19 pandemic.  To transition away from the crisis phase towards a more sustainable approach to long term management of COVID-19.

# COVID-19 vaccines authorized for use in children 5 to 11 years of age
The For further information on NACI's recommendations on the use of COVID-19 vaccines, please refer to National Advisory Committee on Immunization (NACI): Statements and publications and the COVID-19 vaccine chapter in the Canadian Immunization Guide (CIG).
Further information on NACI's process and procedures is available elsewhere (5,6) .

# Table 1. Factors- for consideration to determine the need for and benefit of a booster dose of COVID-19 vaccine in various populations

# Factors- for consideration Evidence reviewed to determine the need for and benefit of a booster dose of COVID-19 vaccine
Risk 

# Recommendations
Please see Table 2 for an explanation of strong versus discretionary NACI recommendations. For further information on these recommendations, please refer to the COVID-19 vaccine chapter in the Canadian Immunization Guide (CIG).

# NACI reiterates previous evidence-informed recommendations for the primary series of
NACI makes the following recommendations on the use of a booster dose in children 5 to 11 years of age. 

# For children 5 to 11 years of age with an underlying medical condition that places them at high risk of severe illness due to COVID

# Considerations on when to offer the first booster dose
- NACI recommends that a first booster dose be offered at an interval of at least 6 months since completion of the primary series or SARS-CoV-2 infection, as more time between exposures may result in a better immune response. A longer interval between doses may result in a better response after any subsequent dose, as this allows time for the immune response to mature in breadth and strength.  In light of a fall 2022 COVID-19 vaccine booster program, a shorter interval of at least 3 months may be warranted. However, a longer interval between vaccine doses may increase immune memory response which may be an important consideration for longterm immunity in children.
- As protection against infection and severe disease is highest soon after vaccine administration, vaccination at a time of low disease incidence may have limited benefit particularly if there is an extended period of time before the next wave of SARS-CoV-2.  A bivalent vaccine containing both the ancestral strain and an Omicron variant of SARS-CoV-2, is anticipated to be available for use in adults in the coming months; however, it is unclear if/when a pediatric bivalent vaccine would become available as trials are still underway. The potential benefits of a new vaccine formulation will need to be weighed against the risk of infection and severe disease while waiting for the vaccine to become available.  There may be variability in how each province, territory and community assesses risk and responds to the needs of their respective jurisdictions, with a focus on protecting those at highest risk for serious outcomes from COVID-19 infection.
NACI continues to monitor and assess the evidence as it emerges and will update its recommendations as needed.

# Summary of evidence
Epidemiology, vaccine coverage, and hybrid immunity  The risk of severe outcomes, including hospitalization, intensive-care unit (ICU) admissions and deaths, is very low in children 5 to 11 years of age compared to other age groups, and lower in children who have a complete primary series than in children who are unvaccinated. These findings have also been observed during the recent Omicron waves. For the four-week period from March 28 to April 24, 2022, the hospitalization rate in children 5 to 11 years of age who received a complete primary series was 0.5/100,000, compared to 0.9/100,000 in unvaccinated children (7) .  Canadian seroprevalence studies from Quebec (January 26, 2022 to February 17, 2022) and British Columbia (March 2022) estimate that 45% to 70% of children 5 to 11 years of age have been previously infected with SARS-CoV-2; most of these infections occurred since Omicron became the dominant variant (8)(9)(10) . Preliminary unpublished data suggests that seroprevalence in individuals less than 17 years of age is higher compared to older age groups (8) . COVID-19 seroprevalence may vary between Canadian jurisdictions.  As of July 17, 2022, 42% of children 5 to 11 years of age are vaccinated with a primary series (11) . Booster dose uptake in those 12 years of age has declined with decreasing age. The proportion of individuals who are vaccinated with a primary series and have received at least one additional dose falls from 90% in adults aged 80 years and older to 19% in adolescents 12-17 years of age.  Hybrid immunity is protection due to a combination of both infection and appropriate vaccination, and has been shown to be more robust than immunity due to infection or vaccination alone. It is expected that children 5 to 11 years of age who have been infe cted with SARS-CoV-2 may optimize their benefit from future vaccine doses by timing them according to the interval since infection, using similar immunological principles to those informing intervals between vaccine doses.

# Vaccine efficacy and vaccine effectiveness and duration of protection following the primary series against Omicron
- The currently available data on vaccine efficacy in the 5 to 11 age group suggest a vaccine efficacy against symptomatic Delta infection of 90.7% shortly after the comple tion of a 2dose primary mRNA vaccination (12) . Protection is lower against Omicron at 51% ~2-3 weeks after vaccination (13,14) . This reflects the reduced protection against Omicron compared to ancestral strain and previous VOCs that has been observed in adolescents and adults. Two additional studies looking at children 5 to 11 years of age fully vaccinated with Pfizer-BioNTech Comirnaty, estimated vaccine effectiveness (VE) of approximately 30% against Omicron infection or SARS-CoV-2 infection during an Omicron-predominant period (14,15) .  Similar to data in adolescents and adults, studies looking at children 5 to 11 years of age are also showing that COVID-19 vaccines offer higher protection against hospitalization and severe disease than against infection. VE estimates against severe disease, including hospitalization due to Omicron infection or SARS-CoV-2 infection during an Omicron predominant period, ranged from 41 to 68% in this age group (15)(16)(17) .  In adults, VE against severe disease with Omicron infection is approximately 90% shortly after a first booster dose and remains above 75% in most studies up to 20 weeks from the first booster (18)(19)(20)(21) . VE against Omicron infection and/or symptomatic disease from a first booster of mRNA vaccine is approximately 60% shortly after the dose and decreases over time since vaccination in most studies (18-20, 22, 23) .  In adolescents 12 to 17 years of age, VE against severe disease with Omicron infection is approximately 66-76% shortly after completion of the primary series and remains between 85-88% in several studies up to at least 25 weeks post-completion of the primary series (24,25) . VE against Omicron infection and/or symptomatic disease after completion of a primary series is approximately 43-75% shortly after the dose and decreases over time since vaccination in most studies (16,17,(24)(25)(26)(27) . No data are available on VE against multisystem inflammatory syndrome in children (MIS-C) due to Omicron infection, however several studies in adolescents 12 to 17 years of age have shown high VE against MIS-C in the pre-Omicron era (28)(29)(30) . 

# Clinical trial summary on

# Immunogenicity
- Immunogenicity was evaluated in a subset of 130 participants (31) . Participants received a booster (third) dose at least 175 days after a two-dose primary series and immune responses were measured 1 month following the booster dose (Dose 3 set). As a comparator, 70 participants were randomly selected from the set who received a two-dose primary series (Dose 2 set) in order to compare immune responses 1 month after Dose 2 to immune responses 1 month after dose 3 from the Dose 3 set. After exclusions (prior evidence of SARS-CoV-2 infection, lack of valid immunogenicity results), immunogenicity data for 67 participants in Dose 3 set and 67 participants in the Dose 2 set were analysed.  In the Dose 3 set, neutralizing antibody geometric mean titres (GMTs) against the reference strain of SARS-CoV-2 (isolated in January 2020) increased by approximately 10-fold 1 month after a booster dose, compared to GMTs immediately prior to booster administration. The seroresponse rate increased from 77.6 % (95% confidence interval : 65.8 to 86.9%) immediately prior to booster administration to 98.5% (95% CI: 92 to 100%) 1 month after booster administration. The geometric mean ratio (GMR) of GMTs 1 month after a booster dose in the Dose 3 set compared to GMTs 1 month after a primary series (Dose 2 set) was 2.17 (95% CI: 1.76 to 2.68%).  Neutralizing antibody titres against Omicron (B1.1.529) after a booster dose were available for 17 participants in the Dose 3 set without evidence of prior infection. O micronspecific titres were approximately 22-fold higher 1 month after a booster dose compared to 1 month after a primary series. In this subset of participants, Omicron -specific titres 1 month after a booster dose were approximately 2.8-fold lower than reference strainspecific titres.

# Safety
- The safety cohort included 401 children 5 to <12 years of age who received a booster (third) dose of Pfizer-BioNTech Comirnaty (10 mcg) COVID-19 vaccine at least 5 months (range 5 to 9 months) after completing a two-dose primary series. The median follow-up time after dose 3 was of 1.3 months (range: 1.0 to 1.8 months). Almost half (47.6 %) of participants were female and the median age at vaccination was 8.0 years. A total of 5.5% of participants were baseline positive for evidence of prior SARS-CoV-2 infection. Safety data are reported for data available up to a cut-off date of March 22, 2022.  The booster dose was well tolerated in children 5 to <12 years of age. Most local and systemic adverse events following immunization (AEFI) were mild or moderate in severity.  The median onset of solicited adverse events was 1-2 days after dose 3 with a median duration of 1-2 days after onset.  After dose 3, AEFIs in decreasing order of frequency were: pain at the injection site, fatigue, headache, muscle pain, swelling, redness, chills, joint pain, fever, diarrhea, and vomiting. No serious adverse events related to the vaccine, no case of MIS-C, myocarditis and/or pericarditis or death were reported. No immediate adverse events were reported within 30 minutes of receiving dose 3 of Pfizer-BioNTech Comirnaty (10 mcg) COVID-19 vaccine.  Local reactions were generally reported at similar frequencies after dose 3 compared with after dose 2 except lymphadenopathy which was reported in 2.5% of vaccinees after dose 3 compared to 0.9% after dose 2. The proportion of participants reporting use of antipyretic/pain medication was higher at dose 3 (30.7%) compared to dose 2 (21.8%).  Systemic events were reported at similar or slightly higher frequencies after dose 3 compared with after Dose 2. The incidence of systemic events among children 5 to <12 years of age after Dose 3 of Pfizer-BioNTech Comirnaty (10 mcg) COVID-19 vaccine was lower than previously observed in adults 18 years of age after dose 3 of Pfizer-BioNTech Comirnaty (30 mcg) COVID-19 vaccine.
Post-market safety surveillance on Pfizer-BioNTech Comirnaty (10 mcg) primary series  Real-world post-market safety data show that the Pfizer-BioNTech Comirnaty primary series is well tolerated in children 5 to 11 years of age, where the majority of AEFIs reported are non-serious, and AEs are less frequently reported than in adolescents 12 to 15 years of age (32)(33)(34)(35) .  Very rare cases of myocarditis and/or pericarditis have been reported following the Pfizer-BioNTech Comirnaty primary series in children 5 to 11 years of age. However, current data suggests the risk of myocarditis and/or pericarditis following mRNA COVID-19 vaccines is substantially lower in children 5 to 11 years of age compared to adolescents.
In the United States, the risk of myocarditis and/or pericarditis within 7 days following dose 2 of Pfizer-BioNTech Comirnaty COVID-19 vaccine was 2.6 cases per million doses in males aged 5 to 11 years (10 mcg dose) compared to 46.4 and 75.9 cases per million doses among males 12 to 15 and 16 to 17 years of age (30 mcg dose), respectively (35) .  Very rare cases of MIS-C have been reported following administration of the Pfizer -BioNTech Comirnaty primary series among individuals aged 5 to 20 years (36)(37)(38) . The rate of MIS-C post vaccination is currently estimated at about 1.1 cases per 1 million doses administered. For some cases, the causal association between the vaccine and MIS-C was unclear as previous history of SARS-CoV-2 infection was also reported (36,37) . While most reports for MIS-C cases were serious and required hospitalization, all described cases had been discharged home and there were no reported deaths. 

# Other considerations

# Implication
A strong recommendation applies to most populations/individuals and should be followed unless a clear and compelling rationale for an alternative approach is present.
A discretionary recommendation may be considered for some populations/individuals in some circumstances. Alternative approaches may be reasonable.