On 29 August 2022 the Therapeutic Goods Administration of Australia granted provisional registration for the Moderna Spikevax Bivalent Original/Omicron BA.1 (subsequently referred to as Moderna bivalent) vaccine for use as a booster dose in people aged 18 years and older.
- The Moderna bivalent vaccine can be used as an alternative vaccine for any booster dose in people aged 18 years or older, according to the current ATAGI recommendations for booster doses.
- ATAGI have made no changes to the current booster recommendations and is not advising any extra booster doses beyond the second booster dose (fourth dose) in selected populations.
- Booster doses of COVID-19 vaccine should be given at least 3 months after the most recent COVID-19 vaccine dose or previous SARS-CoV-2 infection.
- Eligible individuals can receive Moderna bivalent or the original vaccines (various brands) whichever is available to them. Both bivalent and original vaccines result in an improvement in the immune response against BA.1 and BA.4/BA.5 Omicron subvariants, with the Moderna bivalent vaccine showing a small incremental benefit over the original vaccine for Omicron neutralisation.
- Coadministration of Moderna bivalent vaccine with other non-COVID vaccines is acceptable, as per current ATAGI clinical guidance.
- The Moderna bivalent vaccine is not recommended for the primary course of vaccination (first two doses in most people or first three doses in severely immunocompromised people).
- ATAGI does not currently recommend use of the Moderna bivalent vaccine as a booster in anyone under 18 years as it is not registered for this age group.
- As of 28 August 2022, 71.7% of the eligible population have received a 3rd dose (first booster for most people) and 54.4% of eligible people aged 50 years or older have received a second booster dose (fourth dose for most people) which suggests that many people are overdue for a booster dose.1
- ATAGI considers receiving all recommended doses to be a more important factor in obtaining optimal protection against severe COVID-19 than which variant is contained within the dose.2
- While booster vaccination with a variant-containing vaccine may not necessarily 'match' the circulating variant, it is anticipated to induce a broad immune response to current SARS-CoV- 2 variants.3-5
- The Moderna bivalent vaccine is only registered for use as a booster vaccine and contains 50mcg of mRNA, comprising equal quantities encoding the spike protein from the original SARS-CoV-2 virus and Omicron BA.1 variant. The Moderna primary course requires 100mcg doses and therefore the Moderna bivalent vaccine is not considered suitable for primary vaccination. There are no data as yet on the immunogenicity of this bivalent vaccine in a primary series.
- COVID-19 case numbers due to BA.4 and BA.5 Omicron subvariants have now peaked in Australia and are expected to reduce and plateau. There is uncertainty about the timing of any future increase in cases due to the current or new variants and the characteristics of these variants (transmissibility/virulence).
- An assessment of potential benefits, risks and timing of second booster doses, in light of current epidemiology, should be considered in those adults in whom the benefits appear less certain, such as adults aged 30-49 years without other risk factors for severe COVID-19.
- The Moderna bivalent vaccine is presented as a blue-capped multi-dose vial (100 mcg/mL) containing either five 0.5mL doses, or ten 0.5mL doses. The vaccine does not require dilution.
- Each dose should be administered intramuscularly, preferably in the deltoid.
- To minimise the risk of administration errors, providers should preferably prepare and store doses of the Moderna bivalent vaccine separately from other vaccines due to the use of similar coloured vaccine vial caps (such as the Moderna paediatric vaccine 6 months to 5 years formulation). Doses withdrawn in advance of administration should be clearly labelled.
This advice may change
ATAGI continues to monitor evidence on vaccine effectiveness, the epidemiology of SARS-CoV-2 (including its seasonality and emerging subvariants), and on other candidate bivalent COVID-19 vaccines (including BA.4/BA.5 subvariant vaccines). ATAGI will add to its recommendation as further evidence on the bivalent vaccine(s) and knowledge about other uncertainties accumulates.
The Moderna bivalent vaccine generates a modestly higher level of antibody response against multiple SARS-CoV-2 Omicron subvariants (approximately 1.6-1.9 times) including BA.1 and BA.4/BA.5, and a similar antibody response against the original virus, compared with the Moderna original booster vaccine. There remains uncertainty however regarding how this translates to clinical protection. Modelling data suggests that there may be a small increment in protection over an original booster, particularly in those with lower levels of pre-existing immunity, such as people who have only had 2 COVID-19 vaccine doses or who are a longer period from previous infection or vaccination.2 The safety profile of the bivalent vaccine as a booster in adults appears similar to the original vaccine. There are no data on the immunogenicity or safety of the Moderna bivalent vaccine in people under 18 years of age.
Studies monitoring the effectiveness of the vaccine once it is deployed both in Australia and in other countries will provide more data in relation to the protection provided by the bivalent vaccine against infection and severe disease, and the cross-protection it provides against variants/subvariants, including those which differ from those in the vaccine.
Evidence supporting use of the Moderna bivalent vaccine is limited to immunogenicity and safety data from the Moderna P205 study at 4 weeks after a second booster (fourth dose).4,5 Participants aged ≥18 years received Moderna bivalent vaccine as their second booster dose, at least 3 months following a Moderna original primary course (100 mcg doses) and Moderna original first booster dose (50mcg).
Immunogenicity data are available from non-contemporaneous cohorts: 437 people who received the Moderna bivalent vaccine and 377 people who received the Moderna original vaccine as 2nd boosters. There were modestly higher neutralising antibody titres against the Omicron BA.1 variant with the Moderna bivalent vaccine, in people with no previous SARS-CoV-2 infection (1.7 times higher in the bivalent group than the original vaccine group [95% CI 1.5 – 2.0]). In people with prior infection, neutralising titres against BA.1 were 1.9 times higher with the bivalent vaccine (95% CI 1.5- 2.4).
Neutralising antibody titres against the original virus were similar following the Moderna bivalent booster compared with the Moderna original booster in both those with and without previous SARS- CoV-2 infection (1.3 times higher [95% CI 1.1-1.5] and 1.2 times higher [95%CI 1.1 – 1.4], respectively, in the bivalent group).4,5
Cross-protection against variants/subvariants
Evidence suggests the Moderna bivalent vaccine can provide cross-protection against variants and subvariants not included in the vaccine. Neutralisation titres against the BA.4 and BA.5 subvariants were 1.7 times (95% CI 1.5-1.9) higher with the Moderna bivalent vaccine compared with the Moderna original vaccine, although absolute neutralisation titres were lower than those seen against the BA.1 variant.5 Binding antibody levels against previous variants such as Alpha and Delta were also similar or slightly higher with the bivalent vaccine than the original vaccine.4
Duration of protection
While duration of protection is not known with the Moderna bivalent original/Omicron BA.1 vaccine, there is the potential for increased duration of protection as shown by a previous investigational Moderna bivalent vaccine encoding the original virus and the Beta variant, used as a first booster, 6 or more months after a primary Moderna course. This vaccine continued to show higher neutralisation titres than the Moderna original vaccine against multiple variants including Omicron at 180 days after the booster dose.6 It is anticipated that the registered Moderna bivalent original/Omicron BA.1 vaccine may show a similar pattern.
Safety data from clinical trials
The P205 trial (bivalent original/Omicron BA.1)4 and bivalent original/Beta trial6 demonstrate that the safety profile of the Moderna bivalent vaccines was similar to the first or second booster of the Moderna original vaccine, and to the second dose of the primary series of the original vaccine.
The most commonly reported local adverse reactions following a second booster dose of the Moderna bivalent vaccine were injection site pain (77%), fatigue (55%), headache (44%) and myalgia (40%).4 The risk of myocarditis or pericarditis (very rare adverse effects of COVID-19 vaccines) following the Moderna bivalent vaccine has not yet been characterised, as this vaccine has not been used extensively in large populations. However, there is no reason to believe the safety of the Moderna bivalent vaccine is any different to other Moderna mRNA vaccines.
ATAGI will continue to monitor evidence in several areas listed below and update its advice as data accumulate:
- Evidence of clinical protection of the Moderna bivalent vaccine through population-based vaccine effectiveness studies including any incremental benefit of Moderna bivalent vaccine over the original vaccine
- Duration of protection of bivalent vaccines
- Disease epidemiology including emergence of any future variants of concern
- Cross-protection of bivalent vaccines against new variants
- Incremental benefit of BA.4/BA.5-specific vaccines
- Safety of bivalent booster vaccines including rare adverse events such as myocarditis/pericarditis.
Australian Government Department of Health and Aged Care. COVID-19 Vaccine Roll-out. 29 August 2022. Available from: https://www.health.gov.au/sites/default/files/documents/2022/08/covid-19-vaccine-rollout- update-29-august-2022_0.pdf (Accessed 03/09/2022).
- Khoury DS, Docken SS, Subbarao K, et al. Predicting the efficacy of variant-modified COVID- 19 vaccine boosters. medRxiv 2022:2022.08.25.22279237.
- World Health Organization. Interim statement on decision-making considerations for the use of variant updated COVID-19 vaccines. 2022. Available from: https://www.who.int/news/item/17- 06-2022-interim-statement-on-decision-making-considerations-for-the-use-of-variant-updated- covid-19-vaccines (Accessed 1/09/2022).
- Chalkias S, Harper C, Vrbicky K, et al. A Bivalent Omicron-containing Booster Vaccine Against Covid-19. medRxiv 2022:2022.06.24.22276703.
- Moderna Australia Pty Ltd. AUSTRALIAN PRODUCT INFORMATION – SPIKEVAX BIVALENT ORIGINAL/OMICRON (ELASOMERAN/IMELASOMERAN) COVID-19 VACCINE. 2022. Available from: https://www.tga.gov.au/sites/default/files/2022-08/spikevax-bivalent-original-omicron-vaccine- pi.PDF (Accessed 1/09/2022).
- Chalkias S, Eder F, Essink B, et al. Safety, Immunogenicity and Antibody Persistence of a Bivalent Beta-Containing Booster Vaccine. 2022.