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Introduction

ATAGI currently recommends COVID-19 vaccination of children aged 5-11 years with paediatric Comirnaty (Pfizer COVID-19 vaccine for children).

On 17 February 2022, Spikevax (the Moderna COVID-19 vaccine) was provisionally approved by the Therapeutic Goods Administration (TGA) for a two-dose schedule of 50μg per dose in 6 to 11 year old children.

The Pfizer children’s vaccine continues to be the only COVID-19 vaccine approved for children who are 5 years of age.

ATAGI Recommendations and Rationale:

ATAGI recommends Spikevax (Moderna) COVID-19 vaccine can be used for primary vaccination in children aged 6-11 years.

• A clinical trial conducted by Moderna demonstrated that Spikevax produces a strong immune response in children and reduced the likelihood of children developing COVID-19.
• However, ATAGI notes that evidence outside of clinical trials regarding the safety and effectiveness of this vaccine in children in this age group is not yet available.
• The Pfizer COVID-19 vaccine continues to be available and recommended for 5-11 year old children. The Moderna COVID-19 vaccine is an alternative option for children aged 6-11 years. Pfizer remains the only vaccination available for children who are 5 years old. There are currently no vaccines licensed for children aged 4 years and under.
• Side effects reported following the Moderna COVID-19 vaccine have been mild to moderate and transient but may be more common than those following Pfizer COVID-19 vaccine.

ATAGI recommends that immunisation providers are vigilant for the potential for dosing errors with the Moderna vaccine for children.

• There is no paediatric-specific formulation for the Moderna vaccine, there is a risk of dosing, including over-dosing, errors with the Moderna vaccine for children.
• The Moderna 6-11 years dose is half that of the dose used for the primary course for people 12 years and older; but the same as the booster dose (50μg per dose; 0.25mL) for adults.

Schedule:

• The recommended schedule for Moderna vaccination in children 6-11 years is 2 doses (50μg per dose; 0.25mL), 8 weeks apart.
• The interval can be shortened to a minimum of 4 weeks, for children at risk of moderate to severe COVID-19 in special circumstances (as outlined in ).
• A third COVID-19 vaccine dose is recommended for children aged 5 and older who are An mRNA COVID-19 vaccine (either Moderna or Pfizer) is recommended for this third dose (either Pfizer for children 5 years and older or Moderna for children 6 years and older. This dose is recommended to be administered from 2 months after the second dose.
• Children who turn 12 years of age after their first dose should receive the adolescent/adult dose (0.5mL; 100μg) of the Moderna COVID-19 vaccine to complete their primary vaccine course.
• There are currently no published data regarding mixed primary vaccination schedules for children aged

Co-administration

• Paediatric COVID-19 vaccines, including the Moderna vaccine, may be co-administered with other vaccines. Parents and guardians should be aware that this may increase the likelihood of mild to moderate side effects.

Restrictions based on vaccine status

• While vaccination is recommended for children, ATAGI does not support restricting activities for children aged 6 – 11 years who are not vaccinated, or have only received one dose of a COVID-19 vaccine.

Rationale for recommending vaccination

In children aged 6-11 years, SARS-CoV-2 infection is generally asymptomatic or causes a brief illness with mild symptoms.^1,2 Children at increased risk of severe outcomes from COVID-19 include those with pre-existing obesity, chronic pulmonary disease, congenital heart disease and neurological disease, as well as those with neurodevelopmental disorders or epilepsy.^1,3,4 In addition, SARS-CoV-2 infection may be complicated by paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS, also known as MIS-C), a rare and potentially life-threatening syndrome that occurs in approximately 1 in 3,000 children after SARS-CoV-2 infection.^2,5 There is emerging evidence to suggest vaccination in children and adolescents may protect against PIMS-TS.^6,7

The Moderna COVID-19 vaccine demonstrated comparable immunogenicity (for both neutralising antibody and binding antibody) in the pivotal clinical trial in children 6 to 11 years of age (50 mcg per dose) when compared to immunogenicity data in young adults (18 to 25 years, 100 mcg per dose) in a clinical trial demonstrating efficacy. An evaluation of efficacy as a secondary endpoint in the 6 to 11 years Moderna COVID-19 vaccine trial also suggested good protection against COVID-19, noting the overall number of cases available for evaluation was small.

There are currently limited data on the effectiveness of SARS-CoV-2 vaccines in preventing transmission or asymptomatic infection in children. In addition to an anticipated reduction in illness (which is mostly mild), vaccination is also indirectly expected to reduce the need for isolation in children, disruption to education and social activities, and potentially a reduction in parental absenteeism.

At a population level, several modelling studies conducted for earlier SARS-CoV-2 variants have suggested that a vaccination program in young children may indirectly reduce COVID-19-related hospitalisations, admissions to intensive care units (ICU) and deaths in the overall population.^8-10 More details on the indirect and direct benefits of COVID-19 vaccination in children are provided . In December 2021, ATAGI recommended the use of an mRNA vaccine, the Pfizer (Comirnaty) vaccine, for prevention against COVID-19 in children aged 5-11 years, based on these anticipated direct and indirect benefits.

The paediatric formulation of the Pfizer COVID-19 vaccine (Comirnaty) was the first vaccine to be provisionally approved by the Therapeutic Goods Administration for children aged 5 to 11 years in Australia, and has been available since 10 January 2022. As at 17 February 2022, years have received at least one dose of the Pfizer COVID-19 vaccine. Provisional data from AusVaxSafety suggest that this is a well-tolerated vaccine; noting approximately 1 in 4 children have reported at least one adverse event following the first dose. Such side effects were generally mild with pain, swelling, and redness at the vaccination site being the most commonly reported side effects.¹¹

The Moderna COVID-19 vaccine provides an alternative vaccine for children aged 6 to 11 years, administered as a two-dose schedule of 50μg (0.25 mL) per dose, 8 weeks apart. Preliminary data suggest that this vaccine elicits strong antibody responses, and that most side effects are mild to moderate and transient in nature, similar to those observed in children who have received the Pfizer vaccine.

Safety

The Pfizer and Moderna clinical trials differed in how they were designed and how they monitored for side effects which makes it difficult to directly compare the rates of side effects after each vaccine. Side effects were reported more commonly overall in the Moderna COVID-19 vaccine trial compared with the Pfizer trial, but participants who received a placebo dose in the Moderna trial also reported side effects more commonly. A direct comparison of these two paediatric vaccine formulations within a single clinical trial is not yet available.

To help with decision-making parents/carers and health care providers should be aware the short-term adverse events that were more common in the Moderna trial included:

• injection site pain
• lymph node swelling and tenderness
• fever
• headache
• nausea occurred

For example, following the second dose of vaccination with Moderna, 1 in 4 children (24.1%) had a fever, compared to 6.5% of children in the Pfizer trial; and almost 1 in 4 (23.9%) children experienced nausea and vomiting (compared to 1.9% in the Pfizer trial). Furthermore, approximately half (54.2%) of the children experienced headache following their second vaccination in the Moderna trial (compared with 28.0% in the Pfizer trial).

While no cases of myocarditis or pericarditis were reported in the clinical trial of this vaccine conducted by Moderna, this trial was conducted on a relatively small number of children, and this vaccine has not been rolled out broadly in paediatric populations internationally.

Rationale for an extended dosing interval

The manufacturer’s recommended schedule for the paediatric Moderna vaccine is two doses, 28 days apart.

In keeping with the principles outlined in ATAGI’s advice regarding administration of the other mRNA vaccine recommended young children (), ATAGI recommends a schedule of two doses of Moderna vaccine be administered 8 weeks apart for children aged 6-11 years. This extended interval may improve immunogenicity and vaccine effectiveness following the second dose, based on data obtained in adults.^12,13 In addition, this longer dosing interval may reduce the risk of myocarditis and pericarditis, as suggested by a Canadian study among older age groups.¹⁴ Myocarditis and pericarditis are very rare adverse events linked to the use of an mRNA COVID-19 vaccine. Data on the rate of these conditions in young children following Moderna vaccination are not available, but rates of myocarditis and pericarditis in this age group are likely to be lower than that in adolescents. Indeed, real-world evidence using the Pfizer vaccine reveals that for every million doses of Pfizer vaccine administered in male children and adolescents in the US, there are approximately 46 cases of myocarditis in boys aged 12-15 years, compared to only 4 cases for boys aged 5-11 years.¹⁵

It is appropriate to consider shortening the interval in special circumstances to a minimum of 4 weeks, including in those needing a 3rd dose as part of their primary course due to , those at , including NDIS participants, and pre-international travel. Parents and providers are encouraged to weigh up the benefits of earlier protection with the benefit of having a longer dose interval. A dose interval of 8 weeks may improve protection and longevity of protection from the vaccine. A longer interval may also reduce the risk of rare adverse events such as myocarditis.

Issues relating to vaccine administration: Minimising vaccine error risk

The same formulation of the Moderna vaccine is used for adults, adolescents, and children aged 6-11 years; however, the dosage is lower (50μg; 0.25mL) for children under 12 years.

The Moderna vaccine is supplied in multidose vials each containing 5mL providing 10 doses for use for adolescents and adults for a dose of 100μg (0.5mL per dose), or a maximum of 20 doses for use in children aged 6-11 years for a dose of 50μg (0.25mL per dose) for each dose of the primary course. Note, this dose is the same as the dose of 50μg authorised for a booster dose in adults.

It is therefore important to note the risk of dosing, including particularly over-dosing errors with the Moderna COVID-19 vaccine when used in children. Inadvertent administration of a 100μg dose to a child 6-11 years of age is likely to result in an increased risk of adverse reactions, as was observed in the first (dose-finding) part of the clinical trial conducted by Moderna. Should this occur, an report should be submitted using established mechanisms. All AEFI reports are reviewed by the Therapeutic Goods Administration (TGA).

It is also important to note that Moderna is not currently registered for use in children who are under 6 years of age. Therefore, for children who are 5 years old, the only registered vaccination is the paediatric Pfizer vaccine.

Uncertainties and evidence gaps:

At present, there are limited real-world use data available pertaining to the efficacy and safety of the Moderna vaccine in large populations of children, noting that this vaccine has not been used extensively overseas for this age group. Data on immune responses to the Moderna vaccine for children aged 6-11 years, and real-world data on adults immunised with the Moderna vaccine, together indicate that Moderna is likely to be very effective at reducing the likelihood of severe COVID-19 in children, including against the Omicron variant.¹⁶

Preliminary data from older age groups suggest that myocarditis may occur at increased frequency following vaccination with the mRNA vaccines (including the Moderna vaccine),¹⁷