The Com-COV 3 trial is seeking to recruit 270 young volunteers.
The study has already opened at six sites in the UK, and is expanding to nine new recruiting areas, with Cambridge University Hospitals NHS Foundation Trust (CUH) leading the study in the east of England.
All participants will be randomly allocated at the time of their second dose to receive either a full second dose of the Pfizer vaccine, a one-third dose of the Pfizer vaccine, or a full dose of the Novavax vaccine.
These vaccines will be administered at least eight weeks after their first dose.
"Teenagers are currently experiencing the highest rate of infections of all age groups in the UK," said Professor Matthew Snape, associate professor in paediatrics and vaccinology at the Oxford Vaccine Group, and chief investigator on the trial.
“This study will be critical to delivering vital information on the range of options for immunising teenagers against Covid-19 in the UK to help control this.
“We are very grateful to those young volunteers and their parents who have signed up for the study so far. We hope the addition of the trial site at CUH will encourage even more participants to get involved in this critically important research.”
The current UK guidance is that all 12 to 15 year olds receive a single dose of vaccine, while 16 to 17 year olds receive two doses of vaccine, 12 weeks apart.
Younger people at a greater risk of serious illness if they catch Covid are currently offered two doses.
The results from the study will provide the JCVI (Joint Committee on Vaccination and Immunisation) with timely and crucial information about immunising teenagers in the UK.
Dr Theofilos Polychronakis, consultant in paediatric respiratory medicine, who is leading the trial at CUH, said: "We welcome 12-16 year olds from our local community to take part in this study and help us determine the best options for immunisation for all teenagers, everywhere.
“Participation in research by people of Cambridgeshire has always contributed enormously to the discovery of new treatments, particularly over the last two years, and we are extremely grateful to them and all those who help our researchers to make a difference.
“It’s very important that a broad range of people from all parts of the country, and of all ages, take part in research in order to find the most effective solutions to Covid-19 possible."
The study is single-blind and randomised, meaning participants will not know what second dose vaccine they are receiving.
Researchers will assess reactogenicity (any side effects) and immune system responses to these new combinations of vaccines.
Professor Andrew Ustianowski, NIHR Clinical Lead for Covid-19 Vaccination Programme and Joint National Infection Specialty Lead, said:
“By getting involved in this study, volunteers will be able to help researchers develop our understanding of how we can best protect teenagers against Covid-19.
“Thanks to the generosity of thousands of vaccine study participants over the past 18 months, we have been able to reduce the impact and spread of Covid-19 with approved vaccines.
"Once it has reached its target, Com-COV 3 will be a pivotal study that is expected to provide important data that will lead directly to UK guidance on protecting young people and their families.”
If you would like to register to take part in the study at CUH visit the study website at https://comcovstudy.org.uk/participate-cambridge-comcov3
The study is backed through funding from the Vaccines Taskforce and National Institute for Health Research (NIHR) and run across several NIHR-supported sites by the National Immunisation Schedule Evaluation Consortium.