COVID Boosters: Safety and Immunogenicity

Dec 13, 2021
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Authors:
Munro AP, Janani L, Cornelius V, et al.
Citation:
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, Randomized, Controlled, Phase 2 Trial. Lancet 2021;Dec 2:[Epub ahead of print].
Summary By:
Nicole Martin Bhave, MD, FACC

Quick Takes

  • Among 2,878 subjects receiving seven different COVID-19 vaccine boosters, most booster vaccines studied (including Pfizer, Moderna, and Janssen) produced better humoral and cellular responses against SARS-CoV-2 than control meningococcal vaccine.
  • The AstraZeneca booster did not produce a T-cell boosting effect in AstraZeneca-primed subjects.
  • Serious adverse events were rare, and no cases of myocarditis were reported.

Study Questions:

What are the safety and immunogenicity profiles of different coronavirus disease 2019 (COVID-19) vaccine booster regimens?

Methods:

The COV-BOOST (Evaluating COVID-19 Vaccination Boosters) trial was a randomized, controlled phase 2 trial conducted in the United Kingdom to evaluate safety and immunogenicity of seven different COVID-19 vaccine boosters among subjects who received two initial doses of the ChAdOx1 nCov-19 adenovirus-based vector vaccine (AstraZeneca) or BNT162b2 mRNA vaccine (Pfizer). Booster vaccines studied included the following:

  1. Pfizer (full and half dose)
  2. mRNA1237 (Moderna mRNA vaccine, 100 mcg, double the booster dose currently used)
  3. AstraZeneca
  4. NVX-CoV2373 (Novavax nanoparticle vaccine at full and half dose)
  5. VLA2001 (Valneva inactivated virus vaccine at full and half dose)
  6. Ad26.COV2.S (Janssen adenovirus-based vector vaccine)
  7. CVnCoV (CureVac mRNA vaccine, withdrawn from clinical development in October 2021)

The control was MenACWY (Pfizer meningococcal vaccine). Participants were aged ≥30 years, in good health or with mild to moderate comorbidities that were well-controlled, and had no history of laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Enrollment was managed so that approximately one-half of participants were aged ≥70 years, and so that approximately one-half of subjects initially received Pfizer vaccine, and one-half AstraZeneca. Boosters were administered ≥70 days following the second vaccine dose. The coprimary outcomes were immunogenicity (anti-spike protein immunoglobulin G [IgG] at day 28 post-booster) and safety/reactogenicity (occurrence of local and systemic adverse reactions).

Results:

In June 2021, 2,883 subjects were recruited, and 2,878 received a booster dose. More than 90% of subjects were White. Baseline anti-spike IgG levels were higher in Pfizer-primed than AstraZeneca-primed subjects. All study vaccines induced significantly higher levels of anti-spike IgG than control, except for the Valneva booster in Pfizer-primed subjects. Levels of pseudoneutralizing antibodies against delta variant were lower as compared to wild type after all boosters. T-cell-boosting effects were observed with most vaccines, with exceptions of the Valneva booster (regardless of primer), the Novavax booster in Pfizer-primed subjects, and the AstraZeneca booster in AstraZeneca-primed subjects. T-cell responses against beta and delta variants were similar to wild type.

Fatigue and headache were the most common systemic reactions. The Moderna vaccine was more reactogenic than the other mRNA vaccines, causing severe fatigue in 11.6% of AstraZeneca-primed and 5.5% of Pfizer-primed subjects. Reactogenicity was greater in subjects aged <70 years. A total of 24 serious adverse events were reported, including five in the control group; no cases of myocarditis occurred.

Conclusions:

Most booster vaccines studied produced better humoral and cellular responses against SARS-CoV-2 than control meningococcal vaccine. The AstraZeneca booster did not produce a T-cell boosting effect in AstraZeneca-primed subjects. Serious adverse events were uncommon.

Perspective:

These data provide reassurance that the practice of “mixing and matching” (receiving a different booster vaccine than the initial vaccine) does not diminish the immune response to boosters—and in some situations, it may produce a more robust response. The fact that the Pfizer half-dose booster produced immune responses similar to those of the full-dose booster is encouraging, in that vaccine supply could potentially be expanded in resource-poor settings. The side-effect profile of the Moderna booster likely would have been more favorable if the currently recommended 50-mcg dose had been used.

Clinical Topics: COVID-19 Hub, Heart Failure and Cardiomyopathies, Prevention

Keywords: Adenoviridae, Coronavirus, COVID-19, COVID-19 Vaccines, Fatigue, Headache, Immunity, Immunoglobulin G, Meningococcal Vaccines, Myocarditis, Nanoparticles, Primary Prevention, RNA, Messenger, SARS-CoV-2, T-Lymphocytes, Regulatory, Vaccination, Vaccines, Conjugate, Viral Vaccines


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