Vaccines: COVID-19

Authors’ note: Despite changes in variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), vaccines remain very effective in reducing hospitalization and death. While substantial protection against severe outcomes remains after 6 months, protection against symptoms confirmed using reverse transcriptase–polymerase chain reaction (RT-PCR) decreases over time, such that at 6 months there is minimal protection against the current variant.

Recommendations for vaccination to prevent coronavirus disease 2019 (COVID-19) are largely based on the existing epidemiology within a given jurisdiction and on individual-level risk factors. This chapter summarizes vaccine formulations approved in Canada as of the date of the last update of the text. The judgment of professional and international organizations assessing the same body of evidence differs across jurisdictions, which may reflect different confidence in the data and different values and preferences associated with different outcomes. Current eligibility criteria in Ontario: ontario.ca.

Epidemiology, symptoms, diagnosis, and treatment of COVID-19: see Coronavirus Disease 2019 (COVID-19).

Vaccine PlatformsTop

mRNA vaccines currently approved for use against SARS-CoV-2 consist of an mRNA molecule encapsulated in a lipid nanoparticle. The mRNA molecule itself encodes for the SARS-CoV-2 spike glycoprotein. The lipid nanoparticle is cationic and contains cholesterol for stability. Cholesterol is necessary to protect the mRNA from degradation once injected and allows its uptake into cells surrounding the injection site, where endosomal release of the mRNA occurs. The mRNA is then translated into protein by ribosomes in a process that occurs outside—and independently—of the host cell nucleus. The resultant noninfectious SARS-CoV-2 spike glycoproteins are subsequently presented on the host cell surface for immune recognition by circulating lymphocytes. After being used by the cytoplasmic ribosomes to produce the spike glycoprotein, the mRNA is degraded. Of note, it is not biologically plausible for the mRNA component of the vaccine to integrate into human DNA, as human cells lack the reverse transcriptase and integrase enzymes required to accomplish this task.

Protein subunit vaccines currently approved for use against SARS-CoV-2 consist of a recombinant SARS-CoV-2 spike glycoprotein produced in an insect cell line, along with an adjuvant to stimulate the immune response upon injection.

General ConsiderationsTop

1. Role of vaccination in those with previous SARS-CoV-2 infection: The Canadian National Advisory Committee on Immunization (NACI) recommends vaccination to those with previous clinical or microbiologic evidence of SARS-CoV-2 infection, due to the risk of SARS-CoV-2 reinfection and waning immune response over time. Consult local guidance in your jurisdiction regarding the timing of SARS-CoV-2 vaccination following natural infection.

2. Role of microbiologic testing prior to administration of SARS-CoV-2 vaccines: Testing with polymerase chain reaction (PCR), rapid antigen detection tests, or serology are not required prior to immunization with a SARS-CoV-2 vaccine.

3. Postvaccination serologic testing: Serology is not required after immunization with a SARS-CoV-2 vaccine to document seroconversion.

4. Concern for infection with SARS-CoV-2 after immunization with a SARS-CoV-2 vaccine: Receipt of a vaccine does not interfere with PCR or rapid antigen testing for SARS-CoV-2.

5. Variants of concern (VOCs): SARS-CoV-2 has a high baseline rate of mutation due to its RNA genome, allowing “escape mutants” to be produced, which are no longer bound to the same degree by neutralizing antibodies from prior vaccination and may affect vaccine efficacy. VOC nomenclature in this chapter follows the World Health Organization (WHO) classification.

6. Prevention of SARS-CoV-2 transmission by vaccination: Vaccinated individuals may harbor the virus in the nasopharyngeal mucosa but remain asymptomatic. SARS-CoV-2 vaccines reduce the viral load shed from the nasopharynx of vaccinated individuals asymptomatically harboring the virus in the nasopharynx to varying degrees, depending on the infecting strain.

 7. Vaccine interchangeability: The NACI recommends that SARS-CoV-2 vaccines licensed by Health Canada as of the date of the last update of this chapter may be used interchangeably to complete a primary vaccination series, regardless of the vaccine type an individual received as a first dose. One notable exception is in the case of children aged 6 months to <5 years who received a mixed primary series with ≥1 Comirnaty® dose. Such children should receive the total number of recommended doses for a Comirnaty® vaccine schedule.

8. Priority booster dose populations: Seasonal booster doses are recommended for all persons without absolute contraindications to SARS-CoV-2 vaccination. The NACI particularly prioritizes the following groups at increased risk: individuals aged >65 years; long-term care home or congregate living setting residents; pregnant individuals; First Nations, Métis, and Inuit peoples; members of racialized and equity-deserving communities; persons providing essential community services; and those with underlying medical conditions putting them at higher risk of severe COVID-19. The NACI also outlines that 3 populations may receive 2 booster doses in a season: persons aged >65 years, long-term care home or congregate living setting residents, and those >6 months of age with moderate to severe immunocompromise.

Vaccines Currently Approved for Use in CanadaTop

Pfizer-BioNTech Comirnaty® mRNA Vaccine

Comirnaty (marketed by Pfizer-BioNTech; www.canada.ca) contains mRNA encoding for the SARS-CoV-2 spike glycoprotein encapsulated in lipid nanoparticles. Since the initial formulation of the vaccine was studied in large randomized controlled trials (RCTs) when different circulating virus variants were present, the vaccine has been periodically reformulated as new VOCs have emerged.

1. Indications: Comirnaty® is approved for use for the prevention of COVID-19 in patients aged ≥6 months, as both a primary vaccination series and booster immunization.

2. Contraindications: Comirnaty® is contraindicated in those with allergy or hypersensitivity to vaccine components. For further information on vaccine components, consult the Health Canada Product Monograph.

3. Special populations:

1) Pregnant and breastfeeding patients: The NACI recommends that all unvaccinated or previously vaccinated individuals receive one dose of a Health Canada–approved SARS-CoV-2 vaccine at any stage in pregnancy or breastfeeding, provided there are no absolute contraindications. A phase II/III study (ClinicalTrials.gov identifier: NCT04754594) in pregnant patients is ongoing. Data from the Vaccine Adverse Event Reporting System as well as from a systematic review of maternal and fetal outcomes following SARS-CoV-2 vaccination have not shown any obvious safety signals among patients who have received an mRNA vaccine.Evidence 1Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness). Shimabukuro TT, Kim SY, Myers TR, et al; CDC v-safe COVID-19 Pregnancy Registry Team. Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. N Engl J Med. 2021 Jun 17;384(24):2273-2282. doi: 10.1056/NEJMoa2104983. Epub 2021 Apr 21. PMID: 33882218; PMCID: PMC8117969. De Rose DU, Salvatori G, Dotta A, Auriti C. SARS-CoV-2 Vaccines during Pregnancy and Breastfeeding: A Systematic Review of Maternal and Neonatal Outcomes. Viruses. 2022 Mar 5;14(3):539. doi: 10.3390/v14030539. PMID: 35336947; PMCID: PMC8951373.

2) Immunocompromised patients: Patients on immunosuppressive medications or those with moderate or severe immune deficiency may have a diminished serologic response to vaccination (see “Immunization schedule” below).

4. Immunization schedule:

1) Primary series, persons aged ≥12 years: Comirnaty® 30 microg is given as a single 0.3-mL IM injection in the deltoid muscle on day 0. Subsequent booster doses of Comirnaty® 30 microg are recommended after completion of the primary series based on the seasonal circulating virus.

2) Primary series, persons aged 5 to 11 years: Comirnaty® 10 microg is given as a single 0.3-mL IM injection in the deltoid muscle on day 0. Subsequent booster doses of Comirnaty® 10 microg are recommended after completion of the primary series based on the seasonal circulating virus.

3) Primary series, persons aged 6 months to 5 years: Comirnaty® 3 microg is given after dilution as a 0.2-mL IM injection in the deltoid muscle, as a 3-dose series with an 8-week interval recommended between doses.

4) Primary series, immunocompromised patients:

a) For patients aged ≥12 years with moderate or severe immune deficiency, Comirnaty® 30 microg is given as a 0.3-mL IM injection in the deltoid muscle on days 0 and 28 to 56; an additional third dose may be offered, with a recommended interval of 4 to 8 weeks.

b) For patients aged 5 to 11 years with moderate or severe immune deficiency, Comirnaty® 10 microg is given as a 0.3-mL IM injection in the deltoid muscle on days 0 and 28 to 56; an additional third dose may be offered, with a recommended interval of 4 to 8 weeks.

c) For patients aged 6 months to <5 years with moderate or severe immune deficiency, Comirnaty® 3 microg is given after dilution as a 0.2-mL IM injection in the deltoid muscle, as a 4-dose series with an interval of 4 to 8 weeks recommended between doses.

5. Adverse events: Most local and systemic adverse events in clinical trials were mild to moderate and self-limited. Adverse events were more common after the second dose of the vaccine. Most serious adverse events were reported by <2% of the clinical trial participants. In study participants ≥65 years of age, serious adverse events with an incidence ≥2% occurred exclusively after administration of the second dose of vaccine.

Myocarditis after the administration of the original formulation of Moderna Spikevax® (no longer available in Canada), particularly in adolescents and young adults, occurred at a rate of 35 per 1,000,000 doses in patients aged 16 to 17 years, and 20.6 per 1,000,000 doses in patients aged 18 to 24 years. Historically it was recommended that Comirnaty® be used in this age group, however, as the NACI recommendations have moved towards single-dose primary series schedules for COVID-19 vaccination, this product preference has been removed because the adverse event rates are expected to be lower. Data suggest that when myocarditis occurs, it is self-limiting in most cases and does not have long-term sequelae.

Moderna Spikevax® Vaccine

Spikevax® (marketed by Moderna; canada.ca) contains mRNA encoding for the SARS-CoV-2 spike glycoprotein encapsulated in lipid nanoparticles. Since the initial formulation of the vaccine was studied in large RCTs when different circulating virus variants were present, the vaccine has been periodically reformulated as new VOCs have emerged.

1. Indications: Spikevax® is approved for use for the prevention of COVID-19 in patients aged ≥6 months, as both a primary vaccination series and booster immunization.

2. Contraindications: Spikevax® is contraindicated in those with allergy or hypersensitivity to vaccine components. For further information on vaccine components, consult the Health Canada Product Monograph.

3. Special populations:

1) Pregnant or breastfeeding patients: The NACI recommends that all unvaccinated or previously vaccinated individuals receive one dose of a Health Canada–approved SARS-CoV-2 vaccine at any stage in pregnancy or breastfeeding, provided there are no absolute contraindications. Data from the Vaccine Adverse Event Reporting System as well as from a systematic review of maternal and fetal outcomes following SARS-CoV-2 vaccination have not shown any obvious safety signals among patients who have received an mRNA vaccine.Evidence 2Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness). Shimabukuro TT, Kim SY, Myers TR, et al; CDC v-safe COVID-19 Pregnancy Registry Team. Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. N Engl J Med. 2021 Jun 17;384(24):2273-2282. doi: 10.1056/NEJMoa2104983. Epub 2021 Apr 21. PMID: 33882218; PMCID: PMC8117969. De Rose DU, Salvatori G, Dotta A, Auriti C. SARS-CoV-2 Vaccines during Pregnancy and Breastfeeding: A Systematic Review of Maternal and Neonatal Outcomes. Viruses. 2022 Mar 5;14(3):539. doi: 10.3390/v14030539. PMID: 35336947; PMCID: PMC8951373. 

2) Immunocompromised patients: Patients on immunosuppressive medications or those with moderate or severe immune deficiency may have a diminished serologic response to vaccination (see “Immunization schedule” below).

4. Immunization schedule:

1) Primary series, persons aged ≥12 years: Spikevax® 50 microg is given as a single 0.5-mL IM injection in the deltoid muscle on day 0. Subsequent booster doses of Spikevax® 50 microg are recommended after completion of the primary series based on the seasonal circulating virus.

2) Primary series, persons aged 5 to 11 years: Spikevax® 25 microg is given as a single 0.25-mL IM injection in the deltoid muscle on day 0. Subsequent booster doses of Spikevax® 25 microg are recommended after completion of the primary series based on the seasonal circulating virus.

3) Primary series, persons aged 6 months to <5 years: Spikevax® 25 microg is given as a 0.25-mL IM injection in the deltoid muscle on days 0 and 56.

4) Primary series, immunocompromised patients:

a) For patients aged ≥12 years with moderate or severe immune deficiency, Spikevax® 50 microg is given as a 0.5-mL IM injection in the deltoid muscle on days 0 and 28 to 56; an additional third dose may be offered, with a recommended interval of 4 to 8 weeks.

b) For patients aged 5 to 11 years with moderate or severe immune deficiency, Spikevax® 25 microg is given as a 0.25-mL IM injection in the deltoid muscle on days 0 and 28 to 56; an additional third dose may be offered, with a recommended interval of 4 to 8 weeks.

c) For patients aged 6 months to <5 years with moderate or severe immune deficiency, Spikevax® 25 microg is given as a 0.25-mL IM injection in the deltoid muscle in a 3-dose series with an interval of 4 to 8 weeks recommended between doses.

5. Adverse events: Most local and systemic adverse events in clinical trials were mild to moderate and self-limited. Adverse events were more common after the second dose of the vaccine. Most serious adverse events were reported by <2% of the clinical trial participants. In study participants ≥65 years of age, serious adverse events with an incidence ≥2% occurred exclusively after administration of the second dose of vaccine.

Myocarditis after the administration of the original formulation of Moderna Spikevax® (no longer available in Canada), particularly in adolescents and young adults, occurred at a rate of 35 per 1,000,000 doses in patients aged 16 to 17 years, and 20.6 per 1,000,000 doses in patients aged 18 to 24 years. Historically it was recommended that Comirnaty® be used in this age group. However, as the NACI recommendations have moved towards single-dose primary series schedules for COVID-19 vaccination, this product preference has been removed because the adverse event rates are expected to be lower. Data suggest that when myocarditis occurs, it is self-limiting in most cases and does not have long-term sequelae.

NVX-CoV2373 (Novavax) Vaccine

The Nuvaxovid vaccine (marketed by Novavax; canada.ca) consists of recombinant SARS-CoV-2 spike glycoproteins stabilized in prefusion conformation and assembled onto lipid nanoparticles, together with a Quillaja saponaria saponin-based adjuvant. Prior to assembly onto lipid nanoparticles, the recombinant proteins are produced by infecting an engineered baculovirus into moth cell culture. Since the initial formulation of the vaccine was studied in large RCTs when different circulating virus variants were present, the vaccine has been periodically reformulated as new VOCs have emerged.

1. Indications: Nuvaxovid is approved for use for the prevention of COVID-19 in patients aged ≥12 years, as both a primary vaccination series and booster immunization.

2. Contraindications: The Nuvaxovid vaccine is contraindicated in those with allergy or hypersensitivity to vaccine components. For further information on vaccine components, consult the Health Canada Product Monograph.

3. Special populations:

1) Children aged <12 years: The safety and efficacy of the Nuvaxovid vaccine have not yet been established in this population.

2) Pregnant or breastfeeding patients: The NACI recommends that all unvaccinated or previously vaccinated individuals receive one dose of a Health Canada–approved SARS-CoV-2 vaccine at any stage in pregnancy or breastfeeding, provided there are no absolute contraindications.

3) Immunocompromised patients: Patients on immunosuppressive medications or those with moderate or severe immune compromise may have a diminished serologic response to vaccination (see “Immunization schedule” below).

4. Immunization schedule:

1) Primary series, persons aged ≥12 years: Nuvaxovid 5 microg is given as a single 0.5-mL IM injection in the deltoid muscle on day 0. Subsequent booster doses of Nuvaxovid 5 microg are recommended after completion of the primary series based on the seasonal circulating virus.

2) Primary series, immunocompromised patients: For patients aged ≥12 years with moderate or severe immune deficiency, Nuvaxovid 5 microg is given as a 0.5-mL IM injection in the deltoid muscle on days 0 and 28 to 56; an additional third dose may be offered, with a recommended interval of 4 to 8 weeks.

5. Adverse events: Most local and systemic adverse events in both clinical trials were mild to moderate and self-limited. Adverse events were more common after the second dose of the vaccine.