SIX COVID-19 vaccines are safe and boost immunity for people who have had two doses of AstraZeneca or Pfizer-BioNTech, results from the UK-wide COV-BOOST trial show.

Led by University Hospital Southampton and published in The Lancet today, the world-first study was key to shaping the UK booster programme and gives vital evidence for global vaccination efforts.

COV-BOOST looked at the safety, immune responses and side-effects of seven vaccines when used as a third booster jab. It saw 2,878 people aged 30 or over receive one of these boosters 10-12 weeks after their initial two-dose vaccination with either AstraZeneca or Pfizer-BioNTech. A control group was given a meningitis vaccine, to account for reactions not specific to the COVID-19 jabs. [1]

The seven vaccines trialled were:

Oxford-AstraZeneca
Pfizer-BioNTech
Moderna
Novavax
Valneva
Janssen
CureVac

Of these, only AstraZeneca, Pfizer-BioNTech, Janssen and Moderna are currently licensed for use in the UK. Half-doses of Pfizer-BioNtech, Novavax and Valneva were also tested.

Professor Saul Faust, trial lead and Director of the NIHR Clinical Research Facility at University Hospital Southampton NHS Foundation Trust (UHS), said: “Our side effect data shows all seven vaccines are safe to use as a third dose, with acceptable levels of ‘reactogenicity’ – inflammatory side effects like injection site pain, muscle soreness, fatigue. All seven boosted levels of spike protein antibodies significantly after two doses of AstraZeneca. However only six also did so after two doses of Pfizer-BioNTech (AstraZeneca, Pfizer-BioNTech, Moderna, Novavax, Janssen and CureVac). There were also large variations in response with different boosters.

“It’s really encouraging that a wide range of vaccines, using different technologies, show benefits as a booster dose to either of these vaccines. That gives confidence and flexibility in developing booster programmes here and globally, with other factors like supply chain and logistics also in play,” Prof Faust added.

There were large differences in spike protein antibody levels after 28 days across the vaccines. In people who had received two initial doses of AstraZeneca, these ranged from 1.8 times higher to 32.3 times higher with different booster vaccines. For those who had received Pfizer-BioNTech initially, the range was 1.3 times higher to 11.5 times higher. Booster results were similar for those aged 30-69 years and those aged 70 years or older.

The study also looked at immune T-cell responses. T-cells are likely to be important in controlling disease severity, although their impact on overall protection or longevity of immunity is not yet known. COV-BOOST reported T-cell responses in several combinations of initial and booster vaccines, however these were not predictable based on spike protein antibody levels.

Reactions to all seven vaccines were similar, with fatigue, headache, and injection site pain most often reported. These were more commonly reported by those aged 30-69. 912 of the 2,878 participants experienced a total of 1036 adverse events, only 24 of which were severe.

Prof Faust said: “It’s important to note two things about these results. First, they only relate to these vaccines as boosters to the two primary vaccinations, not how well they work as first and second doses. Secondly, the data describe the immune response at 28 days, not vaccine effectiveness. The relationship between that response and long-term protection is still poorly understood. We will be looking at the longer-term immune responses in COV-BOOST, conducting further tests at three months and one year after receiving boosters.

“We are also looking at whether a longer period between second and third doses improves response to the two of the booster vaccines. Several studies have shown this effect between first and second doses. We’ve done that by giving some of our original control participants the booster at a later point, and we expect those results to be available in the new year.”

COV-BOOST was designed so that stored samples can used in evaluating these vaccines’ effectiveness in neutralising any new variants of concern, and COV-BOOST samples have been made available to UKHSA for testing against omicron.

[1] The MenACWY vaccine was used because it can cause similar minor side effects to ChAd and BNT, such as a sore arm, headache, and fever. Saline – which is often used as a control – does not cause any side effects.

University Hospital Southampton-led trial publishes Covid-19 booster data