Results & Publications

Com-COV3

We would like to thank all our Com-COV3 study participants for their invaluable contribution in making this study possible. We will update this webpage whenever we have new information relating to our participants.

The results of the first part of the Com-COV3 study (‘Cohort A’) have now been published in the Journal of Infection and can be read online here.

Across the UK, 148 twelve-to-sixteen-year-olds took part in the Com-COV3 Cohort A study. Participants received the Pfizer-BioNTech vaccine as their first COVID-19 vaccine dose either in the study or just before joining the study. Participants then received either the same vaccine and dose as their first vaccine (i.e., the Pfizer-BioNTech vaccine), a full dose of the Novavax vaccine, or a smaller (one-third) dose of the Pfizer-BioNTech vaccine.

We found that participants who received a smaller (one-third) dose of the Pfizer-BioNTech vaccine as their second vaccine dose experienced slightly fewer side effects than those who received either a dose of Novavax or a second full dose of Pfizer-BioNTech. However, all of the vaccine schedules (Pfizer/Pfizer, Pfizer/Novavax, and Pfizer/Pfizer one-third dose) used in the Cohort A study were well tolerated and any side effects were generally mild and resolved quickly. All of the vaccine schedules used in the study were well tolerated and there were no safety concerns during the study.

We also found that all vaccine schedules used in Cohort A of the study produced a robust immune response. Participants who received either full dose Pfizer-BioNTech or Novavax as their second vaccine had the highest antibody levels at one month after vaccination. However, there was no difference in antibody levels across the study groups by eight months after the second vaccination.

The strongest T cell response was initially seen in those who received Novavax as a second dose (response measured at 14 days after second vaccination). However, like antibody responses, there was no significant difference in T cell responses between the groups by four and a half months after vaccination. T cell responses remained similar across all study groups for the duration of study follow up (i.e., eight months after second vaccination).

Further results from this study show that all study groups developed a strong neutralising antibody response (a type of antibody that defends cells against infection). This response was against both the original COVID-19 and Omicron COVID-19 virus strains. Participants who received either Novavax or full dose Pfizer as their second vaccine had the highest neutralising antibody levels against the original COVID-19 virus strain. Participants who received Novavax had the highest neutralising antibody levels against the Omicron variant, while neutralising antibody levels against Omicron were similar for participants who received either one-third or full dose Pfizer as their second vaccination.

Most COVID-19 infections after vaccination occurred in the one-third Pfizer group, followed closely by the full dose Pfizer group. These results were reviewed by the study’s independent Data Safety and Monitoring Board who advised that no additional COVID-19 vaccine booster doses were required for any participants in the study. This is because infection itself naturally boosts further antibody responses, meaning that any additional vaccine doses would be unlikely to improve the existing immune response.

Rarely, heart inflammation (‘myocarditis/pericarditis’) has been detected after COVID-19 vaccination. We therefore assessed if markers of heart inflammation were present after COVID-19 vaccination using the different study schedules (i.e., when the same vaccine, a different vaccine or a lower dose of vaccine was given as the second dose). However, none of the vaccine schedules used in this study were associated with any markers of heart inflammation (‘myocarditis/pericarditis’).

The results of this study are very important as they show that mixed COVID-19 vaccine schedules (i.e., using a different vaccine or a lower dose of a vaccine as the second dose) are well tolerated and produce excellent immune responses in adolescents. The results also suggest that using a combination of different vaccines (here Pfizer followed by Novavax) provides greater protection against COVID-19 infection. This demonstrates that a more flexible approach to vaccination may be possible, which could potentially improve access to COVID-19 vaccines worldwide, and provide important information that may inform global policy making decisions.

We would like to thank all of our Com-COV3 participants again for their vital contribution to this very important study. We will keep you informed of further publications in the future.

Com-COV & Com-COV2

We would like to thank all our Com-COV and Com-COV2 study volunteers for their participation in these trials. Data from these studies have affected vaccine policy in the UK, and around the world.

Links to all publications arising from these trials can be found on the NISEC website. We will update this page whenever we have new information relating to our participants.

In the Com-COV study we have so far found that immunisation with the two ‘mixed’ schedules (Oxford/AstraZeneca followed by Pfizer or Pfizer followed by Oxford/AstraZeneca) produce antibody and T cell responses higher than that seen after two doses of the Oxford/AstraZeneca, which is known to be a highly effective vaccine schedule against severe disease. Short-term side effects were slightly higher after the second dose in people who receive a “mixed” schedule, but there were no safety concerns raised in the study.

Increasing the ‘priming interval’ (the time between first and second vaccine doses) from four to twelve weeks increased the neutralising antibody response of all four vaccine schedules. The T-cell response, conversely was lower in the 12-week groups. The short-term side-effects seen following vaccination were reduced with a longer priming interval in schedules which had Pfizer as a second dose.

In the Com-COV2 study we found that all the studied mixed-schedules (Oxford/AstraZeneca followed by Novavax or Moderna and Pfizer followed by Novavax or Moderna) produced a robust response both in terms of antibody and T-cells. All combinations produced antibodies that were higher than two doses of the Oxford/AstraZeneca vaccine. Short-term side effects after vaccination were higher in people who had Moderna as a second dose, but not in those who had Novavax.

Further results from Com-COV2 show that immune system antibody responses (neutralising antibodies) against the Omicron variant are lower in people who have had two doses of Oxford/AstraZeneca than two doses of Pfizer COVID-19 vaccine.

The most recent results from Com-COV2 look at how well the immune response is maintained over time. The higher antibody levels that were seen in all schedules fell at approximately the same rate for all schedules.

The antibodies produced by infection and vaccination can have many different functions. One of those functions is ‘neutralisation’, whereby the antibody stops the virus from entering the cell. The Pfizer/Novavax overall had a lower antibody response than Pfizer/Pfizer, but the neutralising antibody response was in fact greater.

The results from both these studies have been very reassuring, as they have shown that mixed vaccine schedules are well tolerated and able to produce robust immune system responses that are at least as good as or higher that of the Oxford/AstraZeneca vaccine – a vaccine that we know has very high real-world protection against severe disease and death.

These results are important because they show that countries can be more flexible in their approach to vaccination, potentially improving access to COVID-19 vaccines.

They also show that there may be subtle but important differences between the vaccines which affect exactly what kind of immune response each combination of vaccines produces, which will inform future vaccine development.

We would like to thank you all again for your participation in Com-COV and Com-COV2. It is greatly valued. The results from the trial are still giving interesting and useful findings. We will keep you informed of further publications in the future.

Although new data produced from these trials is unlikely to have any direct clinical impact on our participants now, we would strongly encourage all our participants to follow government guidance regarding receipt of further vaccine doses.

General information for COVID-19 vaccine trial participants from the National Institute of Health Research can be found here:

https://bepartofresearch.nihr.ac.uk/Vaccine-studies/Latest-vaccine-news/index

The Oxford Vaccine Group