BACKGROUND AND PURPOSE:

• Munro et al. (The Lancet, 2021) investigated the reactogenicity and immunogenicity of seven different COVID-19 vaccines as a third dose after two doses of ChAdOx1 nCov-19 (Oxford–AstraZeneca) or BNT162b2 (Pfizer–BioNtech)

METHODS:

• Multicenter, randomized, controlled phase 2 trial
• Participants
  • >30 years of age
  • No history of laboratory confirmed SARS-CoV-2 infection
  • Time from primary dosing
    • ≥70 days post two doses of AstraZeneca or
    • ≥84 days post two doses of Pfizer
• Interventions
  • Three groups (A, B, and C) across 18 sites
  • Within each group, participants were assigned an experimental vaccine as a third dose, or a control
    • Group A
      • NVX-CoV2373 (Novavax) | Subunit protein vaccine
      • Half-dose of Novavax
      • AstraZeneca | Viral vector vaccine
      • Control: quadrivalent meningococcal conjugate vaccine (MenACWY)
    • Group B
      • Pfizer | mRNA vaccine
      • VLA2001 (Valneva) | Inactivated whole virus vaccine
      • Half-dose of Valneva
      • Ad26.COV2.S (Janssen) | Viral vector vaccine
      • Control: MenACWY
    • Group C
      • Moderna | mRNA vaccine
      • CVnCov (CureVac) | mRNA vaccine
      • Half-dose of Pfizer
      • Control MenACWY
• Study design
  • All participants and investigators were blinded to treatment
  • Primary analysis for immunogenicity was on a modified intention-to-treat basis, and safety and reactogenicity were assessed in the intention-to-treat population
• Primary outcome
  • Safety
  • Reactogenicity and immunogenicity of anti-spike IgG
• Secondary outcomes
  • Viral neutralization
  • Cellular responses

RESULTS:

• 2878 participants
  • AstraZeneca primed patients:
    • Younger age group: Median (IQR) 53 (44 to 61) years
    • Older age group: Median (IQR) 76 (73 to 78) years
    • 46.7% female | 95.4% White
  • Pfizer primed patients
    • Younger age group: Median (IQR) 51 (51 to 59) years
    • Older age group: Median (IQR) 78 (75 to 82) years
    • 53.6% female | 91.9% White

Reactogenicity and immunogenicity

• Three vaccines series showed overall increased reactogenicity
  • Moderna after AstraZeneca
  • Moderna after Pfizer
  • AstraZeneca and Janssen after Pfizer

AstraZeneca Primed Individuals

• Range of IgG levels varied between study vaccines and controls
  • Low: Valneva
  • High: Moderna
• Range in cellular responses
  • Low: AstraZeneca
  • High: Moderna

Pfizer Primed Individuals

• Range of IgG levels varied by vaccine and controls
  • Low: Valneva
  • High: Moderna
• Range in cellular responses
  • Low: Half-dose Valneva
  • High: Moderna

Note:

• The results were similar between those aged 30 to 69 years and ≥70 years
• Vaccines that produced antibodies against the initial wild-type appear to also neutralize delta effectively in vitro “to a consistent, but slightly lesser degree”

Safety 

• Most common local and systemic adverse events
  • Fatigue
  • Pain
• These adverse events were experienced more in people aged 30 to 69 than those ≥70 years
• Serious adverse events were uncommon
  • Control: 5 events
  • Janssen: 2 events
  • Valneva: 5 events
  • Half-dose Valneva: 1 event
  • Pfizer: 1 event
  • Half-dose Pfizer: 2 events
  • AstraZeneca: 2 events
  • CureVac: 1 event
  • Novavax: 2 events
  • Half-dose Novavax: 2 events
  • Moderna: 1 event

CONCLUSION:

• All 7 vaccines tested (AstraZeneca, Pfizer, m1273, NVX, Ad26, CVn, and VAL) boosted immunity following AstraZeneca series
• 6 vaccines (AstraZeneca, Pfizer, m1273, NVX, Ad26, and CVn) boosted immunity following a Pfizer series
• There were no safety issues
• The authors state

These data are consistent with early data from other trials of homologous and heterologous third dose boosters

Learn More – Primary Sources:

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

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