Third dose: finally some results

COVID booster vaccine test results

Results are in from the first randomised, double-blinded, controlled phase 2 clinical trial to look at the safety, immune response and side effects of a third dose of seven COVID-19 vaccines. The trial was conducted by the University Hospital Southampton NHS Foundation Trust in the UK and recently published in The Lancet.

The study included 2,878 participants aged 30 years or older who had received either two doses of AstraZeneca at least 70 days before the booster vaccine or two doses of Pfizer at least 84 days before the booster. None of the participants had a history of laboratory-confirmed SARS-CoV-2 infection or comorbidities.

AstraZeneca, Pfizer, Novavax, Janssen, Moderna, Valneva and Curevac were used as a third (booster) dose.

Researchers separated participants into three groups. Within each group, participants were randomly assigned to a full or a half dose of an experimental vaccine or a control – a quadrivalent meningococcal conjugate vaccine.

All combinations were safe, with adverse reactions similar to those reported for primary and second doses. Complaints included fatigue, headache, and pain at the injection site.

Researchers also looked at the immune response 28 days after a booster vaccine. They found that all study vaccines boosted antibody and neutralising responses when participants had previously received the two AstraZeneca doses. In comparison, those who had initially received Pfizer developed an immune response with all study vaccines except Valneva.

“It’s really encouraging that a wide range of vaccines, using different technologies, show benefits as a third dose to either AstraZeneca or Pfizer-BioNTech,” said Professor Saul Faust, trial lead and director of the NIHR Clinical Research Facility, University Hospital Southampton NHS Foundation Trust. “That gives confidence and flexibility in developing booster programmes here in the UK and globally, with other factors like supply chain and logistics also in play.”

However, the researchers noted significant variations in immune responses depending on the combination of vaccines.

After both two doses of AstraZeneca or two doses of Pfizer, a half dose of Valneva booster gave the lowest immune response, and a full dose of Moderna provided the highest.

Several studies have shown that two doses of AstraZeneca and Pfizer offer 79% and 90% protection against hospitalisation and death after six months.

However, it’s now evident that protection against COVID-19 infection wanes over time. That has driven considerations of booster vaccine effectiveness, particularly with new variants such as Omicron looming over the world.

The substantial variation in the immune responses elicited by each booster vaccine, along with vaccine availability, could help inform policy decisions on boosters.

Results from this first trial are encouraging, but further work is necessary to assess long-term protection and immunological memory generated by the different COVID booster vaccines. The researchers plan to follow up with each participant at three months and one year after the booster vaccine.