Comirnaty™

Name: BNT162b2

Type: Genetic vaccine (messenger RNA/mRNA)

Developer: Pfizer/BioNTech

Likely doses/timing: 2 doses (21 days apart)

Doses for Australia: 10 million doses will be available from early 2021

Manufacturing: Doses for Australia will be manufactured overseas

Storage: Must be stored at -70°C, transported on dry ice and will only last 5 days at standard refrigerator temperatures (2-8°C).

Preparation and Injection: Each multi-dose vial of the vaccine contains 5 doses of 0.3ml. The vaccine must be thawed before injection and diluted with the recommended diluent. After dilution the vial must be used within six hours. The vaccine is administered intramuscularly (IM).

Background

Pfizer/BioNTech’s COVID-19 vaccine (BNT162b2) has been issued Emergency Use Authorization (EUA) and even full approval in several counties. Of note, the UK and USA have both issued an EUA, on 2 December and 11 December 2020, respectively. The first injections under a country-wide program began in the UK on 8^th  December 2020.

Pfizer’s BNT162b2 vaccine contains messenger RNA (mRNA) which codes for the SARS-CoV-2 full-length spike protein. Although mRNA vaccines have never been licensed before, they had already been studied for more than a decade. mRNA vaccines were already under development for other viruses, such as influenza, and have been tested and shown to be safe in previous clinical trials.

On 25 January 2021, the Pfizer/BioNTech COVID-19 vaccine (Comirnaty) was the first COVID-19 vaccine to be granted provisional registration in Australia.

Clinical trials

Pre-clinical trials were conducted in non-human primates (rhesus macaques) and mice. In animal models, the vaccine induced a strong immune response and prevented lung infection. Vaccinated primates, who were challenged with SARS-CoV-2 virus, had no virus detected in the lower respiratory tract and clearance of virus in the nose within three days. These results indicated the vaccine may reduce both infection and transmission.

Phase 1/2 clinical trials were conducted in Germany and USA. The US Phase 1 trial also included older participants (up to 85 years old) and compared placebo to one of two vaccine candidates (BNT162b1, which encoded the SARS-CoV-2 receptor-binding domain; or BNT162b2, which encodes the SARS-CoV-2 full-length spike). This trial supported the selection of BNT162b2 for advancement to Phase 2/3 trials.

Phase 2/3 clinical trials of BNT162b2 were conducted across USA, Germany, Argentina, Brazil, South Africa and Turkey, and started in July 2020. Initial results of the Phase 3 trial from 43,448 participants, aged 16 years or older, were published in the New England Journal of Medicine on 10 December 2020.

Safety profile

The reactogenicity of BNT162b2 was generally mild or moderate, reactions were generally short-term and were less common and milder in older adults, compared to younger adults. Systemic reactions were more common and severe after the second dose. The incidence of serious adverse events was low and similar in both the vaccine and placebo groups. Phase 3 trial results were consistent with earlier clinical studies and provided results from a median follow-up time of two months after the second dose.

Mild-to-moderate pain at the injection site within seven days after an injection was the most commonly reported local reaction (66-83% depending on age group or first versus second dose). Pain resolved within 1-2 days, there was no increase in reported local reactions after the second dose and no reactions required emergency department visit or hospitalisation.

The most commonly reported systemic events were fatigue (59%), headache (52%) and muscle aches (37%), after the second dose among younger vaccine recipients. These proportions were lower in older vaccine recipients; 51% with fatigue, 39% with headache and 29% with muscle aches after the second done. Severe systemic events were reported in less than 2% of vaccine recipients after either dose, except for fatigue (in 3.8%) and headache (in 2%) after the second dose.

In younger vaccine recipients, fever (≥ 38°C) was reported in 4% after the first dose and 16% after the second dose. In older recipients, fever was reported in 1% and 11%; after first and second dose respectively. Systemic events including fever and chills were observed within the first 1-2 days after vaccination and resolved shortly thereafter.

Serious adverse events were rare; only four were reported among BNT162b2 recipients (shoulder injury related to vaccine administration, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, and right leg paraesthesia). No stopping rules (trial pauses) were met during the reporting period. Safety monitoring for this vaccine will continue for 2 years after administration of the second dose of vaccine.

Since public vaccinations began in December 2020, anaphylactic reactions in people receiving the Pfizer/BioNTech COVID-19 vaccine have been reported in the United Kingdom and United States. Clear guidance regarding allergy management will be provided once the Pfizer/BioNTech vaccine has regulatory approval from the TGA. Some guidance from the CDC is included in the following links:

1. Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Pfizer-BioNTech COVID-19 Vaccine — United States, December 14–23, 2020
2. Interim Clinical Considerations for Use of mRNA COVID-19 Vaccines Currently Authorized in the United States
3. Lab Tests to Collect Shortly After Severe Allergic Reaction/Anaphylaxis Following COVID-19 Vaccination.

Immunogenicity

Two doses of BNT162b2 elicited high SARS-CoV-2 neutralising antibody titres and robust spike protein-specific T-cell responses. These neutralising antibody responses were greater than the responses measured in people recovered from natural COVID-19 infection; in both younger and older adults. The duration of protection is currently unknown, with booster doses not recommended at this stage.

Vaccine efficacy

The Pfizer/BioNTech vaccine was the first to present interim data of their Phase 3 trial, indicating the vaccine had 95% vaccine efficacy. Similar vaccine efficacy (generally 90 to 100%) was observed across all subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of co-existing conditions. Older adults, 65 years and over, also had the same vaccine efficacy as younger adults.

In among 36,523 participants who had no evidence of existing or prior SARS-CoV-2 infection, there were only 8 cases of COVID-19 (with onset at least seven days after the second dose) in those vaccinated with BNT162b2, compared to 162 cases of COVID-19 among those who received placebo. This corresponded to 95% vaccine efficacy. When combined with participants who did have evidence of past SARS-CoV-2 infection, the vaccine efficacy was still similar (94.6%).

The vaccine appears likely to provide individual protection and prevent severe disease; among 10 cases of severe COVID-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient.

Less than two weeks after the first dose, the vaccine started protecting participants, and the second dose three weeks later, boosted their immune response. The study was not designed to assess the efficacy of a single-dose regimen, however, in the interval between the first and second doses, the observed vaccine efficacy against COVID-19 was 52%, reaching full efficacy at least seven days after the second dose.

Ongoing research

Phase 3 trials are still ongoing and safety monitoring for this vaccine will continue for two years after administration of the second dose of vaccine. Safety monitoring will also continue in the post-licensure phase through surveillance of adverse events following immunisation reporting systems.

Further Phase 3 trials are underway or planned in children (underway for adolescents 12 years and older and planned for younger children), pregnant women and special risk groups, such as immunocompromised people.

Ongoing data collection is required to assess whether the vaccine prevents transmission and asymptomatic cases, as well as assessing how long immune memory may last and whether booster doses are required.

This vaccine has not yet been assessed in clinical trials when co-administered with other vaccines; hence the vaccine should be administered alone. The USA’s CDC recommends a minimum interval of 14 days before or after administration with any other vaccines, including seasonal influenza. ATAGI recommends a 14 day minimum interval between the administration of influenza and COVID-19 vaccines [refer to: ATAGI advice on influenza and COVID-19 vaccines].

Resources

• Pfizer: Our progress in developing an investigational COVID-19 vaccine
• CDC: Pfizer/BioNTech COVID-19 vaccine
• CDC: Interim Clinical Considerations for Use of mRNA COVID-19 Vaccines Currently Authorized in the United States
• NEJM: Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates
• NEJM: Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine