Pfizer/BioNTech COVID-19 vaccine

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 8th  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

Authors: Daniela Say (MVEC Immunisation Fellow) and Nigel Crawford (Director SAEFVIC, Murdoch Children’s Research Institute)

Date: January 2021

Materials in this section are updated as new information and vaccines become available. The Melbourne Vaccine Education Centre (MVEC) staff regularly reviews materials for accuracy.

You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family’s personal health. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult a healthcare professional.

 

 


Breastfeeding and immunisations

MVEC is supportive of breastfeeding at the time of childhood immunisations as well as the immunisation of breastfeeding mothers when vaccines are indicated.

In this reference page, we detail the different types of vaccines recommended for breastfeeding women and describe when a more detailed discussion with your healthcare provider is warranted.

Immunising breastfeeding mothers will not impact their ability to produce breastmilk. Inactivated (e.g. seasonal influenza and whooping cough) and live-attenuated vaccines (e.g. measles-mumps-rubella) are generally safe to administer to women who are breastfeeding.

In some instances, antibodies created by the mother in response to a vaccine can be passed onto the infant via breastmilk (passive immunity) to be absorbed orally and provide short term protection. Any maternal antibodies passed onto a baby via breastmilk does not interfere with a baby’s immune response to their own vaccines.

In addition, there are no concerns for a breastfeeding mother to have contact with someone who has recently received either a live-attenuated or an inactivated vaccine.

Influenza

Annual influenza immunisation is safe and recommended for breastfeeding mothers. Babies less than 6-months of age are at greatest risk from disease yet cannot receive influenza vaccines until they are 6-months of age. Maternal immunisation will provide protection for mothers as well as providing some passive protection for babies through the secretion of antibodies until they are old enough to receive their own influenza vaccine [refer to MVEC: Influenza vaccine recommendations].

Measles-mumps-rubella (MMR)

The MMR vaccine is a live-attenuated vaccine and therefore immunisation should be avoided in the 28 days prior to a pregnancy and is contraindicated during pregnancy. However, it is safe for immunisation to occur at any time following delivery including whilst breastfeeding with no concerns for the mother or the breastfed infant.

COVID-19 vaccines

Women who are breastfeeding can receive COVID-19 vaccines. Whilst there is limited data on the administration of COVID-19 vaccines in women who are breastfeeding, there are no safety concerns relating to its administration to women who are breastfeeding women or for their babies.

Hepatitis B

It is safe for mothers who are positive for the hepatitis B virus to breastfeed their baby as long as the infant receives a dose of hepatitis B immunoglobulin (HBIG) at birth as well as all scheduled doses of hepatitis B vaccine commencing with the birth dose.

Yellow fever vaccines

The live-attenuated yellow fever vaccination should be avoided in breastfeeding mothers. Anyone travelling to a yellow fever endemic area should have a specialist travel consultation to provide individual travel advice and discuss immunisation recommendations. There is some evidence to suggest that yellow fever vaccine virus can be transmitted to infants via breastmilk. Infants are not recommended to receive the yellow fever vaccine until a minimum of 9-months of age due to its side effects profile [refer to Australian Immunisation Handbook: Yellow fever].

Resources

There are a lot of excellent resources that review the evidence and support the administration of routine vaccines to breastfeeding mothers.

Authors: Dr Nigel Crawford (Director SAEFVIC, Murdoch Children’s Research Institute), Rachael McGuire (MVEC Education Nurse Coordinator) and Georgina Lewis (Clinical Manager SAEFVIC, Murdoch Children’s Research Institute)

Date: August 2020

Reviewed by: Rachael McGuire (MVEC Education Nurse) February 2021

Materials in this section are updated as new information becomes available. The Melbourne Vaccine Education Centre (MVEC) staff regularly review materials for accuaracy.

You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family’s personal health. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult a healthcare professional.


BCG vaccine

Background

Tuberculosis (TB) is a disease caused by the bacteria called Mycobacterium tuberculosis. It is spread via droplets through coughing and sneezing. It primarily affects the lungs, however it can spread to the lymph nodes, the brain, kidneys, or spine. Common symptoms of pulmonary TB include fever, cough, chest pain and night sweats.

TB infection can be categorised as having active disease (displaying symptoms and being infectious) or latent TB infection (the bacteria is dormant, there are no symptoms, and the patient is not infectious). Latent TB can become active if an infected person’s immune system becomes weakened.

Australia has one of the lowest rates of TB disease in the world, but it remains very common in some countries, including places Australians frequently travel to visit friends and relatives (VFR).

About BCG vaccine

The BCG vaccine is a live-attenuated vaccine. It was developed from a bacteria similar to TB called Mycobacterium bovis and is weakened so that it will not cause disease in healthy humans.

The BCG vaccine does not prevent someone being infected with the bacteria that causes TB, but it can prevent the development of serious disease. It is specifically designed to prevent TB in children and can be given from birth onwards.  The World Health Organization (WHO) currently recommends a single lifetime dose.

How to administer BCG

The BCG is given intradermally as a single dose of vaccine and can only be administered by a medical or nursing professional who is trained in BCG vaccination working within a recognised BCG clinic [see resources].

The recommended site of vaccination is on the left arm over where the deltoid muscle inserts into the humerus. Administration at this site will minimise the risk of keloid scarring.

If active eczema, dermatitis or psoriasis is present at the site of injection, vaccination should be deferred until the skin can be treated and is clear of symptoms.

Who should be immunised?

In Australia, the BCG vaccine is recommended for specific groups:

  • Aboriginal and Torres Strait Islander neonates living in Queensland
  • Children < 5-years of age living in Aboriginal and Torres Strait Islander communities in Queensland
  • Children < 5-years travelling to endemic countries

When travelling to endemic countries BCG should be administered at least 4-6 weeks prior to departure, to ensure vaccine effectiveness prior to exposure.

Tuberculin skin testing (TST/Mantoux)

Tuberculin skin testing (TST) or Mantoux testing, involves the intradermal injection of a tuberculin purified protein derivative (PPD). Everyone ≥ 6-months of age should have a TST performed prior to BCG vaccination to identify if a person already has a level of immunity to TB. In people who have previously received a BCG or have previously had TB exposure, a hypersensitivity reaction can be recognised 48-72 hours later.

It is important to note that TST results may be unreliable for 4-6 weeks following a measles infection or receiving a measles-containing vaccine.

What to expect following BCG vaccine

BCG, like all vaccines, has a list of common and expected side effects and a list of rare side effects that may occur in the weeks following [refer to What to expect following the BCG vaccination- RCH parent handout for more information].

Common/expected reactions:

  1. A small red papule will appear at the injection site in the weeks following the vaccine
  2. An ulcer (open sore) may develop 2-3 weeks later (usually less than 1 cm in diameter) and last from a few weeks to months
  3. The majority of infants will develop a flat scar at the site once the ulcer heals.

Rare of more serious side effects:

  1. Axillary lymphadenopathy (swelling of the lymph nodes under the left arm)
  2. Persisting ulcer lasting longer than a few months
  3. A large abscess (collection of pus) at the injection site
  4. Keloid scarring at the site

If you suspect a rare or serious side effect, it is strongly recommended to seek medical advice either from a GP or the medical clinic where the BCG was administered. 

For specialist immunisation advice or to report an Adverse Event Following Immunisation (AEFI), please contact SAEFVIC.

Refer to the useful resources and links below to find out more about the BCG vaccine. 

Resources

BCG Clinics in Victoria

Useful links

Authors: Nigel Crawford (Director SAEFVIC, Murdoch Children’s Research Institute) and Rachael McGuire (SAEFVIC Research Nurse, Murdoch Children's Research Institute)

Reviewed by: Mel Addison (SAEFVIC Research Nurse, Murdoch Children's Research Institute), Rachael McGuire (SAEFVIC Research Nurse, Murdoch Children's Research Institute) and Francesca Machingaifa (SAEFVIC Research Nurse, Murdoch Children's Research Institute)

Date: August 2020

Materials in this section are updated as new information and vaccines become available. The Melbourne Vaccine Education Centre (MVEC) staff regularly reviews materials for accuracy.

You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family’s personal health. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult a healthcare professional.