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COVID-19 boosters increase immunity

Friday December 3rd 2021

Six different types of COVID-19 boosters are safe and increase immunity following vaccination with either the AstraZeneca or Pfizer-BioNTech jabs, British researchers report today.

A randomised, phase 2 trial of COVID-19 booster vaccines found seven increased immunity when given ten to 12 weeks after two doses of the Oxford-AstraZeneca. Six increased immunity following two doses of Pfizer-BioNTech.

However, the trial identified large variations in antibody and cellular immune responses between the vaccines.

The UK trial involved 2,878 adults aged 30 years and older and it assessed immune response, rather than effectiveness in protecting against infection or severe disease.

Writing in The Lancet, the researchers say two doses of ChAdOx1-nCov19 - the Oxford–AstraZeneca - and BNT162b2, Pfizer-BioNTech, have shown 79% and 90% protection, respectively, against hospitalisation and death after six months in several studies.

However, protection against COVID-19 infection wanes over time.

The COV-BOOST study looked at immunogenicity and reactogenicity of seven vaccines - ChAd, BNT, NVX-CoV2373 (Novavax [NVX]), Ad26.COV2.S (Janssen [Ad26]), Moderna [mRNA1273], VLA2001 (Valneva [VLA]), and CVnCov (Curevac [CVn]) - used as a third booster jab.

’Confidence and flexibility’

Professor Saul Faust, trial lead and director of the NIHR Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, said the side effect data show all seven vaccines are safe to use as third doses.

All seven boosted spike protein immunogenicity after two doses of AstraZeneca, while Pfizer-BioNTech, Moderna, Novavax, Janssen and Curevac boosted spike immunogenicity after two doses of Pfizer-BioNTech.

“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 Faust.

“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.”

He added that the 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,” he said.

“We are also studying two of the vaccines in people who had a later third dose after seven to eight months although results will not be available until the new year.”

Trial participants, about half of whom were aged 70 and over, had received their first doses of ChAd or BNT in December 2020, January or February 2021, and second doses at least 70 days before enrolment for ChAd and at least 84 days for BNT.

About half of the participants received two doses of ChAd and half two doses of BNT. The control vaccine used was a meningococcal conjugate vaccine (MenACWY).

Thirteen experimental and control arms of the trial, comprising seven vaccines plus three at half dose and three control arms, were split into three groups, with six sites per group.

Group A received NVX, half dose NVX, ChAd, or a control. Group B received BNT, VLA, half dose VLA, Ad26 or a control. Group C received Moderna, CVn, which was withdrawn from further clinical development in October 2021, half dose BNT, 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 to wild type, alpha, beta, and delta variants.

Increases in anti-spike protein antibody levels after 28 days varied across the vaccines. After two doses of ChAd, these ranged from 1.8 times higher to 32.3 times higher according to the booster vaccine used, while after two doses of BNT the range was 1.3 times higher to 11.5 times higher. Significant T-cell responses were reported in several combinations.

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

Diverse patterns of protection

However, the researchers 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.

A second UK study yesterday warned that the population will have “diverse” patterns of protection against the virus, depending on which variants they have been exposed to.

Researchers at Imperial College and Queen Mary College in London reported in Science on the effect of immune system imprinting by different sequences of spike proteins from the virus.

The findings come from a study of 731 healthcare workers in London.

Professor Rosemary Boyton, from Imperial’s Department of Infectious Disease, said the findings showed the benefit of a third dose of booster vaccine.

She said: “Our first encounter with spike antigen either through infection or vaccination shapes our subsequent pattern of immunity through immune imprinting.

“Exposure to different spike proteins can result in reduced or enhanced responses to variants further down the line. This has important implications for future proofing vaccine design and dosing strategies.”

Dr Joseph Gibbons, from Queen Mary University of London said: “The emergence of new variants with the potential to evade immunity has shown that we must future-proof the next-generation of vaccines. We studied immunity over time in people infected with different variants and found that vaccine responses are highly variable depending on the infecting strain. These findings can be used to ensure vaccine design is optimal.”

Munro APS, Janani L, Cornelius V et al. Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial. Lancet 3 December 2021

[abstract]

Reynolds, Gibbons and Pade et al. Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants. Science 2 December 2021

[abstract]

Tags: Flu & Viruses | Pharmaceuticals | UK News

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