Booster dose of six Covid vaccines safe, increases immunity: Lancet study

Six different COVID-19 boosters are safe and elicit strong immune response in people who have previously received a two-dose course of AstraZeneca or Pfizer vaccines, according to a study published in The Lancet journal.

Two doses of AstraZeneca and Pfizer vaccines have shown 79 per cent and 90 per cent protection, respectively, against hospitalisation and death after six months in several studies, the researchers said.

However, protection against COVID-19 infection wanes over time, which has driven consideration of boosters to protect the most vulnerable and lessen pressure on health services.

The latest study looked at safety, immune response and side-effects of seven vaccines when used as a third booster jab.

The vaccines studied were AstraZeneca, Pfizer-BioNTech, Novavax, Janssen, Moderna, Valneva, and Curevac.

"The side effect data show all seven vaccines are safe to use as 3rd doses, with acceptable levels of inflammatory side effects like injection site pain, muscle soreness, fatigue," said Professor Saul Faust, trial lead from the University Hospital Southampton NHS Foundation Trust, UK.

"Whilst all boosted spike protein immunogenicity after two doses of AstraZeneca, only AstraZeneca, Pfizer-BioNTech, Moderna, Novavax, Janssen and Curevac did so after two doses of Pfizer-BioNTech," Faust said.

The researchers noted that these results relate only to these vaccines as boosters to the two primary vaccinations, and to the immune response they drive at 28 days.

Further work will generate data at three months and one year after people have received their boosters, which will provide insights into their impact on long-term protection and immunological memory, they said.

A randomised, phase 2 trial of the seven booster vaccines was conducted, with the third doses given 10-12 weeks after initial two-dose courses of AstraZeneca or Pfizer-BioNTech.

The trial involved 2,878 participants in good health recruited at 18 UK sites between June 1 and June 30, 2021.

Around half of participants received two doses of AstraZeneca and half two doses of Pfizer.

The control vaccine used was a meningococcal conjugate vaccine (MenACWY).

Participants were aged 30 years or older, with approximately half aged 70 years or older.

Thirteen experimental and control arms of the trial were split into three participant groups, with six sites per group.

Group A received Novavax, half dose Novavax, AstraZeneca, or a control. Group B received Pfizer, Valneva, half dose Valneva, Janssen or a control.

Group C received Moderna, Curevac, which was withdrawn from further clinical development in October 2021, half dose Pfizer, or a control.

Primary outcomes were adverse effects seven days after receiving a booster, and levels of antibodies targeting the spike protein on the surface of COVID-19 virus cells which enables them to enter human cells after 28 days, compared to controls.

Secondary outcomes included the response of T cells -- which play a key role in the immune response to viral infection, and seem important in controlling disease severity -- to wild type, Alpha, Beta, and Delta variants.

Both antibody-mediated immunity and T-cell response are known to be important in vaccine effectiveness, the researchers said.

Increases in anti-spike protein antibody levels after 28 days varied across the vaccines.

After two doses of AstraZeneca these ranged from 1.8 times higher to 32.3 times higher according to the booster vaccine used.

After two doses of Pfizer the range was 1.3 times higher to 11.5 times higher.

Significant T-cell responses were reported in several combinations, the researchers said.

At 28 days, all booster results were similar for participants aged 30-69 years and those aged 70 years or older, they said.

The authors warn that the boost ratios should be interpreted with caution because they relate to immunogenicity rather than protection against disease, and the relationship between antibody levels at day 28 and long-term protection and immunological memory is unknown.

Reactions to all seven vaccines were similar, with fatigue, headache, and injection site pain most often reported.

The authors highlighted several limitations to the study.

Due to pandemic timelines and the need to generate data to inform policy in September 2021, the interval between second and third doses was shorter in some participants than between their first two doses.

Several studies have shown that a longer time period between the first and second doses may improve immunogenicity, including improved antibody responses when the initial BNT doses are spaced by 12 weeks rather than three weeks.

This could mean that the boost in immunity is lower than if longer dose intervals had been used, the researchers added.