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Boosters significantly strengthen immunity — Cov-Boost trial

Those boosted with the Pfizer vaccine after two doses of AstraZeneca had antibody levels a month later nearly 25 times higher than controls. When the Pfizer booster was given after two Pfizer shots, antibody levels rose more than eightfold, found the UK-based Cov-Boost trial in The Lancet.

The most potent booster in the study was a full dose of the Moderna vaccine, which raised antibody levels 32-fold in the AstraZeneca group and 11-fold in the Pfizer group.

The researchers measured immune responses in nearly 3,000 people who received one of seven COVID-19 boosters or a control jab two to three months after their second dose of either AstraZeneca or Pfizer vaccine.

“These are remarkably effective immunological boosters, way above what is needed to prevent hospitalisation and death,” said Prof Saul Faust, the trial lead and director of the NIHR clinical research facility at University Hospital Southampton NHS Foundation Trust, reports The Guardian.

Beyond antibodies, the scientists looked at the impact of boosters on T- cells – another crucial component of the immune system linked with the prevention of severe disease. Most of the boosters, including Pfizer, Moderna and AstraZeneca, increased T-cell levels regardless of the vaccine people had for their first two doses.

The scientists also noted that the T-cell response was as good against the Beta and Delta variants of concern as against the original virus that emerged from Wuhan.

Jonathan Ball, professor of molecular virology at the University of Nottingham, who was not involved in the study, said: “While variants, such as the Delta variant, reduced the overall virus-killing effect of antibodies, the T-cell responses were pretty much unaffected,” he said. “That the mRNA vaccine boosts gave a marked increase in both antibodies and T-cells is great news, especially with the emergence of the Omicron variant.

Early results from the Cov-Boost study underpinned the decision by the Joint Committee on Vaccination and Immunisation to shorten the time people had to wait for a booster from six to three months. The study found AstraZeneca to be an effective booster too, raising antibody levels three and five times after primary vaccination with AstraZeneca and Pfizer respectively.

Further results from the study suggest that booster programmes could switch to half-doses of the Pfizer vaccine without losing much protection. The data shows that half-doses of Pfizer boosted antibody levels in the AstraZeneca group nearly 17 times and more than six times in those who had Pfizer for their first two shots.

Study details

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

Alasdair P S Munro, Leila Janani, Victoria Cornelius, Parvinder K Aley, Gavin Babbage, Prof David Baxter, et al.

Published in The Lancet on 2 December 2021

Summary

Background
Few data exist on the comparative safety and immunogenicity of different COVID-19 vaccines given as a third (booster) dose. To generate data to optimise selection of booster vaccines, we investigated the reactogenicity and immunogenicity of seven different COVID-19 vaccines as a third dose after two doses of ChAdOx1 nCov-19 (Oxford–AstraZeneca; hereafter referred to as ChAd) or BNT162b2 (Pfizer–BioNtech, hearafter referred to as BNT).

Methods
COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of third dose booster vaccination against COVID-19. Participants were aged older than 30 years, and were at least 70 days post two doses of ChAd or at least 84 days post two doses of BNT primary COVID-19 immunisation course, with no history of laboratory-confirmed SARS-CoV-2 infection. 18 sites were split into three groups (A, B, and C). Within each site group (A, B, or C), participants were randomly assigned to an experimental vaccine or control. Group A received NVX-CoV2373 (Novavax; hereafter referred to as NVX), a half dose of NVX, ChAd, or quadrivalent meningococcal conjugate vaccine (MenACWY) control (1:1:1:1). Group B received BNT, VLA2001 (Valneva; hereafter referred to as VLA), a half dose of VLA, Ad26.COV2.S (Janssen; hereafter referred to as Ad26) or MenACWY (1:1:1:1:1). Group C received mRNA1273 (Moderna; hereafter referred to as m1273), CVnCov (CureVac; hereafter referred to as CVn), a half dose of BNT, or MenACWY (1:1:1:1). Participants and all investigatory staff were blinded to treatment allocation. Coprimary outcomes were safety and reactogenicity and immunogenicity of anti-spike IgG measured by ELISA. The primary analysis for immunogenicity was on a modified intention-to-treat basis; safety and reactogenicity were assessed in the intention-to-treat population. Secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ISRCTN, number 73765130.

Findings
Between June 1 and June 30, 2021, 3498 people were screened. 2878 participants met eligibility criteria and received COVID-19 vaccine or control. The median ages of ChAd/ChAd-primed participants were 53 years (IQR 44–61) in the younger age group and 76 years (73–78) in the older age group. In the BNT/BNT-primed participants, the median ages were 51 years (41–59) in the younger age group and 78 years (75–82) in the older age group. In the ChAd/ChAD-primed group, 676 (46·7%) participants were female and 1380 (95·4%) were White, and in the BNT/BNT-primed group 770 (53·6%) participants were female and 1321 (91·9%) were White. Three vaccines showed overall increased reactogenicity: m1273 after ChAd/ChAd or BNT/BNT; and ChAd and Ad26 after BNT/BNT. For ChAd/ChAd-primed individuals, spike IgG geometric mean ratios (GMRs) between study vaccines and controls ranged from 1·8 (99% CI 1·5–2·3) in the half VLA group to 32·3 (24·8–42·0) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·1 (95% CI 0·7–1·6) for ChAd to 3·6 (2·4–5·5) for m1273. For BNT/BNT-primed individuals, spike IgG GMRs ranged from 1·3 (99% CI 1·0–1·5) in the half VLA group to 11·5 (9·4–14·1) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·0 (95% CI 0·7–1·6) for half VLA to 4·7 (3·1–7·1) for m1273. The results were similar between those aged 30–69 years and those aged 70 years and older. Fatigue and pain were the most common solicited local and systemic adverse events, experienced more in people aged 30–69 years than those aged 70 years or older. Serious adverse events were uncommon, similar in active vaccine and control groups. In total, there were 24 serious adverse events: five in the control group (two in control group A, three in control group B, and zero in control group C), two in Ad26, five in VLA, one in VLA-half, one in BNT, two in BNT-half, two in ChAd, one in CVn, two in NVX, two in NVX-half, and one in m1273.

Interpretation
All study vaccines boosted antibody and neutralising responses after ChAd/ChAd initial course and all except one after BNT/BNT, with no safety concerns. Substantial differences in humoral and cellular responses, and vaccine availability will influence policy choices for booster vaccination.

The Lancet article – 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 (Open access)

The Guardian article – Covid booster shots significantly strengthen immunity, trial finds (Open access)

 

See more from MedicalBrief archives:

 

After Israel dropped the vaccine ball, boosters show signs of taming Delta

 

FDA green-lights third jab for immunocompromised people

 

CDC panel backs third Pfizer and Moderna shot for the immunocompromised

 

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