Three COVID-19 vaccines are being administered in Australia; two messenger RNA (mRNA) vaccines (Pfizer/Comirnaty and Moderna/Spikevax and one viral vector vaccine (AstraZeneca/Vaxzeveria). Another viral vector vaccine approved (Johnson & Johnson/Janssen) but not available in Australia Novavax/Biocelect is a protein vaccine that is anticipated to be available in Australia if approved.

Key points:

• The AstraZeneca, Pfizer, and Moderna vaccines are safe and effective for protecting against COVID-19 infection, illness, hospitalisation, severe illness, and death.
• The priority for protecting people from COVID-19 is to achieve high two-dose vaccine coverage for all eligible community members.
• While it is likely that booster doses will be necessary for all eligible people aged over 18 years, members of high-risk groups should be prioritised to receive boosters if it has been six months or longer since their last dose.
• High-risk groups include; people aged 50 years and older, people with underlying conditions such as chronic illness, cancer, immunosuppression use, or obesity, residents of aged care and disability facilities, Aboriginal and Torres Strait Islander adults, and people at increased occupational risk of COVID-19 such as health and aged care workers.
• While their effectiveness decreases over time, vaccine protection is still greater than not having a vaccine at all, especially for people in high-risk groups
• While risk of severe or critical illness is low amongst fully vaccinated people, older age and pre-existing conditions increase the risk of experiencing severe illness and possible risk of death.
• Emerging evidence suggests that a third dose of Pfizer, Moderna, or AstraZeneca vaccines may offer enhanced and prolonged protection against illness particularly for older people and people at risk of more severe illness.
• Currently in Australia, Pfizer is recommended as the preferred booster dose irrespective of the primary vaccine the person first received.
• AstraZeneca can be used for those who had received the same vaccine previously with no contraindications or precautions for use or those who experienced a severe reaction following a previous mRNA vaccine.
• Currently, Moderna is still under consideration for third dose use in Australia with other vaccines such as Novavax likely to be considered in the future.

Introduction

COVID-19 vaccination is recommended for all people aged ≥12 years. In Australia, Moderna/Spikevax and Pfizer/Comirnaty are approved for use for people aged ≥12 years. AstraZeneca/Vaxzeveria is only approved for people aged ≥18 years, but for people aged under 60 years, Pfizer/Comirnaty is preferentially recommended by the Australian Technical Advisory Group on Immunisation (ATAGI). The Australian Government Department of Health publishes recommendations and guidance for administration of the vaccines. Currently, all COVID-19 vaccines in Australia are administered via a two-dose schedule of the same vaccine unless otherwise indicated (eg. people with a contraindication to a second dose).

Booster shots/third doses

Following the Therapeutic Goods Administration (TGA’s) approval, on 28 October, ATAGI released Australian recommendations on the use of a booster dose of COVID-19 vaccine. The ATAGI has said that while Australia’s first priority must be to achieve high two-dose vaccine coverage, booster shots are recommended for people aged 18 and older in following groups:

• Those at increased occupational risk of COVID-19 (eg. health, disability, and aged care workers in frequent or prolonged contact with COVID-19 patients).
• People aged 50 years and older.
• People with underlying medical conditions that increase their risk of worse outcomes.
• Residents of aged care and disability facilities.
• Aboriginal and Torres Strait Islander adults.

People in these groups are most likely to benefit from a booster dose by reducing risk of severe illness, hospitalisation, and death or through reducing likelihood of infection and occupation-related impacts (eg. absences due to sickness). In Australia, the Pfizer/Comirnaty vaccine will first be offered to people in the above high-risk groups who have received their last (second) dose at least six months earlier. For people who had received two doses of AstraZeneca/Vaxzeveria with no contraindications or precautions for use and for those who experienced a severe reaction following a previous mRNA vaccine, AstraZeneca/Vaxzeveria may be administered as a booster. Currently, Moderna/Spikevax is still under consideration for third dose use in Australia with other vaccines such as Novavax/Biocelect likely to be considered in the future. The ATAGI has also recommended that the third dose may be administered at the same time as an influenza vaccine. While the one-dose Johnson & Johnson/Janssen vaccine is not available in Australia, a booster may be administered at least six months after one dose (eg. for people who received the vaccine overseas). People who received mixed doses (eg. one dose of AstraZeneca/Vaxzeveria followed by one dose of Pfizer/Comirnaty or Moderna/Spikevax ) can receive a booster dose six months after the second dose. At this stage, only people who have received vaccines that are approved for use in Australia will be eligible to receive a booster.

All TGA-approved COVID-19 vaccines are effective in reducing a person’s risk of becoming infected, sick, hospitalised, severely ill, being admitted to an intensive care unit, dying, and transmitting the virus, including the Delta variant, to others.^1-6 The vaccines however do not completely protect a person from harm or prevent transmission which is why all current official recommendations regarding infection prevention and control including public health advice and local restrictions on public/social activities should continue to be observed.

Why is a booster shot necessary?

Like other vaccines, the effectiveness of COVID-19 vaccines wanes over time.^4,7,8 Some countries including Germany, Israel, Turkey, China, Uruguay, Cambodia, Thailand, United Kingdom, the United Arab Emirates, Russia, and the United States now provide booster shots.^9,10 In most cases, booster doses are initially only offered to people who are at high risk of exposure and worse outcomes including those with pre-existing conditions, severely compromised immune systems, older people, and health and aged care workers and nursing home residents.¹⁰ In Israel a third dose of Pfizer is approved for people aged 60 and older and who have received a second dose at least five months previously.¹¹ In the United States, a Pfizer booster is recommended for people aged 65 and older.¹² In Turkey and Uruguay booster doses of Pfizer are being offered to people who initially received one of China’s Sinovac or Sinopharm vaccines.¹⁰ In Thailand and Cambodia AstraZeneca is recommended as the third dose.¹⁰ Most of the limited number of studies so far examine the effectiveness of a third dose of mRNA vaccine,^11,12 however some evidence does suggest that a third dose of AstraZeneca may confer improved immune responses to infection.¹³

Because only a few countries have begun administering a third dose to certain population groups, participant numbers in studies of safety and effectiveness vary widely from around 20 to over a million. From a study in Israel with 1,137,804 participants, a booster dose of the Pfizer vaccine was found to significantly reduce the risk of confirmed COVID-19 infection and the likelihood of experiencing severe illness at least 12 days following the third dose.¹¹ In a study from the United States with 23 participants, a third dose of Pfizer was administered resulting in a similar degree of mild to moderate local reactions and systemic effects as following dose 2 and evidence of prolonged and improved immunity.¹² Despite the possibility of waning effectiveness and vaccine ‘breakthrough’ infections (infection at least 14 days after the second vaccine dose), vaccination still effectively protects most recipients from severe or critical illness.¹⁴  Older people and those with pre-existing conditions such as chronic disease, obesity, or suppressed or compromised immune systems appear more likely to experience severe or critical illness after two doses.¹⁴ In a United Kingdom study examining a third dose of AstraZeneca, 75 people who had received a second dose with an interval of eight to 16 weeks were investigated, revealing that 28 days after a third dose antibody levels against SARS-CoV-2 alpha, beta, and delta variants were higher than following the second dose.¹³

While emerging evidence suggests that a third dose does confer greater protection from infection and severe illness than two doses,^11,12,13 due to access and availability limitations there are concerns that redistributing doses for boosters could divert these doses from administration for people’s first or second doses, leaving them vulnerable.¹⁵ This is particularly concerning in terms of global equity as wealthier nations moving towards a three dose schedule may compromise low and middle income nations from accessing one or two doses for their people. A further issue with this is that countries or regions where fewer people can be vaccinated may become areas where COVID-19 persists for longer resulting in prolonging the pandemic further.

Despite the emerging evidence of the safety effectiveness of third dose booster shots, some warn of implementing widespread booster administration until after more robust and extensive evidence is gathered and analysed.¹⁶ At this stage, the benefits of third dose booster shots do not appear to outweigh the benefits of providing initial protection via one or two doses. This means that because of the very well-established effectiveness of the vaccines’ two dose regime, ATAGI has recommended that the primary focus in Australia should be on getting as many people vaccinated with their first and second doses as a priority.¹⁷ Once this has been achieved to an agreed level, consideration could move to offering a third dose for at risk populations when more evidence has emerged and vaccine access and availability has improved.¹⁷ Australia should also explore options to better assist neighbouring countries with poorer access and vaccine coverage, as improving vaccine uptake in less well-resourced countries will also help to lessen the duration and severity of the pandemic and risk to Australia from international outbreaks.

With increased availability and access to vaccines, as the pandemic and vaccine roll out progresses in Australia and internationally, and as new evidence emerges regarding the safety and effectiveness of third dose, booster shots may be considered in Australia particularly for those at highest risk of worse outcomes as well as frontline health and aged care staff who are also at high risk due to increased exposure.¹⁷

Disclaimer: Evidence is continually emerging regarding the effectiveness and safety of COVID-19 vaccines. There is an increasing volume of strong evidence for safety and effectiveness of the vaccines in standard two-dose form, but relatively less for three-dose regimens.

References

1. Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N Engl J Med 2020; 383(27): 2603-15.
2. Voysey M, Clemens SAC, Madhi SA, et al. 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. Lancet 2021; 397(10269): 99-111.
3. Lopez Bernal J, Andrews N, Gower C, et al. Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. New England Journal of Medicine 2021; 385(7): 585-94.
4. Baden LR, El Sahly HM, Essink B, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. New England Journal of Medicine 2020; 384(5): 403-16.
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6. Tenforde M, Olson S, Self W, al. e. Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Among Hospitalized Adults Aged ≥65 Years — United States, January–March 2021. MMWR Morb Mortal Wkly Rep 2021; 28 April.
7. Thomas SJ, Moreira ED, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine through 6 Months. New England Journal of Medicine 2021.
8. Iacobucci G. Covid-19: single dose of Pfizer and Oxford vaccines cuts risk of hospital admission by 80% in over 80s, data suggests. BMJ 2021; 372: n612.
9. Callaway E. COVID vaccine boosters: the most important questions. Nature 2021; 5 Aug.
10. Mahase E. Covid-19 booster vaccines: What we know and who’s doing what. BMJ 2021; 374: n2082.
11. Bar-On YM, Goldberg Y, Mandel M, et al. Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel. New England Journal of Medicine 2021.
12. Falsey AR, Frenck RW, Walsh EE, et al. SARS-CoV-2 Neutralization with BNT162b2 Vaccine Dose 3. New England Journal of Medicine 2021.
13. Mahase E. Covid-19: Third vaccine dose boosts immune response but may not be needed, say researchers. BMJ 2021; 373: n1659.
14. Juthani PV, Gupta A, Borges KA, et al. Hospitalisation among vaccine breakthrough COVID-19 infections. The Lancet Infectious Diseases.
15. Maxmen A. COVID boosters for wealthy nations spark outrage. Nature 2021; 30 Jul.
16. Krause PR, Fleming TR, Peto R, et al. Considerations in boosting COVID-19 vaccine immune responses. The Lancet.
17. (ATAGI) ATAGoI. ATAGI statement about the need for additional doses of COVID-19 vaccines. 2021. https://www.health.gov.au/news/atagi-statement-about-the-need-for-additional-doses-of-covid-19-vaccines (accessed 24 Sept 2021).

Author:
Micah DJ Peters PhD works at the the National Policy Research Unit (Federal Office), Australian Nursing and Midwifery Federation (ANMF) and the University of South Australia, Clinical and Health Sciences, Rosemary Bryant AO Research Centre