The Journal of Clinical Investigation (May 2023)

Durability of immune responses to mRNA booster vaccination against COVID-19

  • Prabhu S. Arunachalam,
  • Lilin Lai,
  • Hady Samaha,
  • Yupeng Feng,
  • Mengyun Hu,
  • Harold Sai-yin Hui,
  • Bushra Wali,
  • Madison Ellis,
  • Meredith E. Davis-Gardner,
  • Christopher Huerta,
  • Kareem Bechnak,
  • Sarah Bechnak,
  • Matthew Lee,
  • Matthew B. Litvack,
  • Cecilia Losada,
  • Alba Grifoni,
  • Alessandro Sette,
  • Veronika I. Zarnitsyna,
  • Nadine Rouphael,
  • Mehul S. Suthar,
  • Bali Pulendran

Journal volume & issue
Vol. 133, no. 10

Abstract

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Background Maintaining durable immunity following vaccination represents a major challenge, but whether mRNA booster vaccination improves durability is unknown.Methods We measured antibody responses in 55 healthy adults, who received a booster dose of the Pfizer-BioNTech or Moderna vaccine against SARS-CoV-2 and calculated the half-life of the antibody titers. We also measured memory B and T cell responses in a subset of 28 participants. In 13 volunteers who received a second booster vaccine, we measured serum antibody titers and memory B and T cell responses.Results The booster (third immunization) dose at 6 to 10 months increased the half-life of the serum–neutralizing antibody (nAb) titers to 76 days from 56 to 66 days after the primary 2-dose vaccination. A second booster dose (fourth immunization) a year after the primary vaccination further increased the half-life to 88 days. However, despite this modestly improved durability in nAb responses against the ancestral (WA.1) strain, there was a loss of neutralization capacity against the Omicron subvariants BA.2.75.2, BQ.1.1, and XBB.1.5 (48-, 71-, and 66-fold drop in titers, respectively, relative to the WA.1 strain). Although only 45% to 65% of participants demonstrated a detectable nAb titer against the newer variants after the booster (third dose), the response declined to below the detection limit in almost all individuals by 6 months. In contrast, booster vaccination induced antigen-specific memory B and T cells that persisted for at least 6 months.Conclusion The durability of serum antibody responses improves only marginally following booster immunizations with the Pfizer-BioNTech or Moderna mRNA vaccines.

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