Exploring the safety profiles of each vaccine in circulation

One year ago, almost to the day, the World Health Organization officially declared a pandemic and the world sat back, unarmoured, as everything fell into a frightening unfamiliarity. Businesses closed their doors, supermarket shelves were emptied, and the streets of once-thriving city centres became desolate.

The prospect of a vaccine gave many of us hope and we watched with bated breath as media announcements grew evermore promising. Five months after the first vaccine manufacturer issued its first media release, in November, two vaccines have now made it onto Australian shores, with full Therapeutic Goods Administration (TGA) approval: the Pfizer–BioNTech and AstraZeneca formulas.

But amid the chinking of champagne glasses, some are still hesitant to roll up their sleeves for a jab, concerned that a formula tipped to take three or more years could be ready so quickly. With that in mind, we explored the safety profiles of these vaccines.

Potential for flu-like symptoms

Pfizer and BioNTech’s vaccine belongs to the mRNA family and AstraZeneca’s to the adenovirus vector. Both are effectively gene therapies, as they manipulate cells in the body to produce the viral spike protein. This contrasts with the traditional method of making vaccines from either inactivated virus or synthetic protein.

Although both Pfizer and AstraZeneca COVID-19 vaccines were deemed by the TGA to have safety profiles in large-scale clinical trials suitable for conditional approval,^1,2 they do come with side effects.

“Synthetic mRNA can generate toxicity, as foreign RNA within cells is interpreted by the body as if it was a viral infection. In response, the cells produce inflammatory signals that cause temporary but sometimes severe flu-like symptoms such as fevers, weakness and muscle aches,” said Dr Nikolai Petrovsky, Professor in the College of Medicine and Public Health at Flinders University.

On the positive side, people who received the Pfizer vaccines in clinical trials were up to 95% less likely than unvaccinated people to develop symptoms of COVID-19.³ In contrast, those who received the AstraZeneca vaccine were just 62–90% less likely to develop symptoms,⁴ suggesting a much more modest effect.

The risk–benefit ratio of each vaccine must also be considered, as potential side effects differ between individual formulas.

Adverse reactions

Anaphylaxis is a heightened possibility with the mRNA vaccines. These contain ‘polyethylene glycol’, a known allergen, explaining why the rate of anaphylactic reactions is approximately 10 times that of influenza vaccines.⁵

“This appears to be an allergic reaction to the molecules that the mRNA is packaged into. It’s well known that people can have allergies to these types of molecules,” Dr Petrovsky said.

There has been no suggestion to date that AstraZeneca’s vaccine causes a higher-than-normal rate of allergies, so this might be the preferred vaccine of the two for those with known severe allergies, he added.

All centres administering mRNA vaccines should have adrenaline available to treat any anaphylactic reactions in those unlucky enough to experience one.

Theoretical risks in pregnancy

No vaccine is ever assumed to be safe in pregnancy, until proven otherwise, particularly those based on gene therapies — like the Pfizer and AstraZeneca formulas.

“Although the flu vaccine is now regarded as safe to give during pregnancy, we simply don’t know enough about the interaction these new types of vaccines may have with the foetus and the placenta,” Dr Petrovsky said.

Since pregnant women are automatically excluded from standard clinical trials, it is unlikely we will have clarity on this any time soon, although Pfizer has recently announced that it is trialling its mRNA vaccine in pregnant women at over 24 weeks of gestation.

In the meantime, pregnant women are being omitted from the vaccination program.

Safety margin

It is important that approved vaccines have a wide safety margin to ensure that there are minimal risks, even in the event of an overdose. The Pfizer vaccine recently demonstrated this, when two aged-care residents in Australia were erroneously given four times the recommended dosage by a doctor who has now been struck off.

The 88-year-old man and 94-year-old woman were hospitalised as a precaution, but showed no signs of adverse reaction.⁶

Antibody-dependent disease enhancement

While some previous coronavirus vaccines, including those for SARS, could actually make infections worse, this has fortunately not been seen with COVID-19 vaccines, Dr Petrovsky said.

“As we accumulate data over time, this will become more certain, but at the moment things look encouraging,” he said.

As with any new technology there is a hypothetical risk of harm, but these risks should be tightly managed and made public through data sharing and regulatory and manufacturer warnings.

“TGA approval is not granted unless they have assessed that the overall benefit of these vaccines significantly outweigh the risks,” Dr Petrovsky concluded.

In other words, anyone invited to do so by authorities should have enough confidence to roll up their sleeves.

References

1. Australian public assessment report for BNT162b2 (mRNA). https://www.tga.gov.au/sites/default/files/auspar-bnt162b2-mrna-210125.pdf
2. COVID-19 vaccine: AstraZeneca ChAdOx1-S. https://www.tga.gov.au/covid-19-vaccine-astrazeneca-chadox1-s
3. The Advisory Committee on Immunization Practices’ Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine — United States, December 2020. https://www.cdc.gov/mmwr/volumes/69/wr/mm6950e2.htm?s_cid=mm6950e2_w
4. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext
5. Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Pfizer-BioNTech COVID-19 Vaccine — United States, December 14–23, 2020. https://www.cdc.gov/mmwr/volumes/70/wr/pdfs/mm7002e1-H.pdf?ACSTrackingID=USCDC_921-DM45827&ACST
6. Elderly patients show no adverse reactions after being given incorrect dose of COVID-19 Pfizer vaccine. https://www.abc.net.au/news/2021-02-25/coronavirus-queensland-covid-vaccine-dosage-error-aged-care/13188724

Image credit: ©stock.adobe.com/au/Marina Zlochin