Com-COV vaccine study to research third dose booster options for 12-to-15-year-olds

• Com-COV 3 to test multiple options for third booster dose COVID-19 vaccines for young people aged 12 to 15 years
• Participants immunised with two doses of Pfizer-BioNTech vaccine to receive either a:

further full adult dose Pfizer-BioNTech vaccine (30 mcg)
one-third adult dose Pfizer-BioNTech vaccine (10 mcg)
full child dose Pfizer-BioNTech vaccine (10 mcg)
full dose Novavax vaccine
meningitis vaccine, followed by a dose of Pfizer-BioNTech COVID-19 vaccine later in the study (control group)

• Researchers to assess reactogenicity and immunogenicity of vaccine schedules

Researchers running the University of Oxford-led Com-COV programme have launched a further study of COVID-19 vaccination schedules in young people aged 12 to 15 – with a focus on assessing different options for a third dose booster vaccination.

The Com-COV 3 study has been commissioned through the NIHR and backed by £2.8 million government funding, with support from both the Vaccine Taskforce and National Institute for Health and Care Research (NIHR). This new stage of the study – which will look to enrol 380 volunteers – is funded entirely by the Coalition for Epidemic Preparedness Innovations (CEPI) and will run across nine NIHR-supported sites plus one Health and Care Research Wales site by the National Immunisation Schedule Evaluation Consortium (NISEC). All participants will have completed a two-dose schedule of the Pfizer-BioNTech vaccine, at least three months before joining. Researchers will deliver a third vaccine dose as part of the study.

Matthew Snape, Professor in Paediatrics and Vaccinology at the University of Oxford, and Chief Investigator of the trial, said:
‘This study builds on the important results from previous Com-COV and COV-BOOST studies, which have directly informed the national and international use of mixed COVID-19 vaccine schedules. These studies have included teenagers receiving the first two vaccine doses.

‘A key question for teenagers now is how well they respond to different options for a third dose of vaccine. This includes giving a lower dose of the Pfizer-BioNTech vaccine, or a protein-based vaccine produced by Novavax. If these can be shown to produce a strong immune response with fewer temporary side effects, then this could improve the acceptability and uptake of a third dose adolescent campaign, both in the UK and internationally.’

All participants will be randomly allocated to receive either a full adult dose, one-third adult dose or full child dose of the Pfizer-BioNTech vaccine, or a full dose of the Novavax vaccine. A control group will receive a meningitis vaccine (Bexsero, against MenB bacteria) followed by a Pfizer-BioNTech COVID-19 vaccine later in the study.

Professor Matthew Snape added: ‘So far, NISEC COVID vaccine studies have enrolled more than 12,000 participants in the UK, providing unique data on best use of licensed COVID vaccines that have directly influenced policy in the UK and globally.
‘This new stage of the Com-COV 3 study is the next step in this programme, and we gratefully acknowledge the incredible support of the UK public for these studies, along with that of the NIHR, Vaccine Taskforce and CEPI.’

The study is single-blind and randomised. This means participants will not know what third dose vaccine they are receiving until three months after their vaccine dose. Researchers will analyse reactogenicity (any side effects) and immune system responses to these new combinations of vaccines. They will also examine if a one-third adult dose of the Pfizer-BioNTech vaccine is at least as good as a full child dose of the same vaccine.

Professor Andrew Ustianowski, NIHR Clinical Lead for COVID-19 Vaccination Programme and Joint National Infection Specialty Lead, said:
‘It's very important that continued research into how we can best protect teenagers against COVID-19 takes place. The Com-COV 3 study will help us to develop a better understanding of adolescents’ immunity when it comes to booster jabs.
‘Thousands of volunteers are still stepping forward for a number of vaccine booster studies, two years on since we began to recruit into the first COVID-19 vaccine studies. Their time, support and generosity have been immense and helps us build upon the science of vaccine combinations. The latest stage of the Com-COV 3 study will be key to providing important data on protecting young people and their families.’
Dr Jakob Cramer, Director of Clinical Development, Vaccine R&D, CEPI, said: ‘Clinical research on mix-and-match and fractional dose vaccination strategies have provided very relevant evidence on pragmatic recommendations on vaccine use in both high-income countries and low- and middle-income country settings.
‘However, gaps remain in our understanding of the impact of such approaches for booster doses in under 15s – a group that accounts for around a quarter of the world’s population. The key additional evidence supplied through Com-COV 3 could help guide global vaccination programmes and ensure as many people as possible be protected from this dreadful disease.’

Stanley C. Erck, President and Chief Executive Officer, Novavax, said: ‘Novavax’s vaccine has already shown strong immune responses against COVID-19 and its variants and we look forward to confirming NVX-CoV2373’s efficacy as a booster through the Com-COV3 programme.
‘Vaccine choice is important for both primary vaccination and boosters, and this trial is another step towards offering more options to individuals, healthcare providers, and public health authorities.’
The study investigators anticipate reporting initial results in 2022. The UK’s regulatory body, the Medicines and Healthcare products Regulatory Agency (MHRA), rigorously assess the safety and efficacy of any new vaccine before considering market authorisation and subsequent rollout to patients. The Joint Committee on Vaccination and Immunisation (JCVI) provide expert guidance to UK health departments on vaccination, which takes into account a range of evidence, including data from trials undertaken to understand the immunological impact of booster vaccinations.
All those who are interested can register via the study website: comcovstudy.org.uk

A brief Com-COV timeline
The University of Oxford is leading the NIHR-commissioned Com-COV 3 study, run by the National Immunisation Schedule Evaluation Consortium (NISEC) and backed by £2.8 million of government funding. CEPI also provided £2.4 million to support the study as part of its COVID-19 research programme, which aims to address current gaps in current clinical knowledge of vaccine performance both now and in the long term in order to expand access to COVID-19 vaccines as part of the global vaccination rollout.

In May 2021, researchers reported preliminary Com-COV data revealing more frequent mild to moderate reactions in mixed schedules compared to standard schedules, however, these were short-lived in duration. In June 2021, they further reported that ‘mixed’ schedules involving Pfizer-BioNTech and Oxford-AstraZeneca induced high concentrations of antibodies against the SARS-CoV2 spike IgG protein when doses were administered four weeks apart.

In April 2021, the researchers expanded the programme to include the Moderna and Novavax vaccines in a new study, and reported results in December supporting these vaccines as second dose options following a first dose of the Oxford-AstraZeneca or Pfizer-BioNTech vaccines.

The first stage of the Com-COV3 study in adolescents was conducted from August 2021 and showed that fewer temporary side effects were observed with a reduced dose of the Pfizer/BioNTech vaccine as a second dose, while still generating a robust immune response. These results have been presented to the JCVI and are being prepared for publication.

In line with CEPI’s equitable access policy, findings generated through the research will be shared through open-access publications and via scientific meetings to ensure all can benefit.