Durability of immune responses to mRNA booster vaccination against COVID-19
Prabhu S. Arunachalam, … , Mehul S. Suthar, Bali Pulendran
Prabhu S. Arunachalam, … , Mehul S. Suthar, Bali Pulendran
Published March 23, 2023
Citation Information: J Clin Invest. 2023;133(10):e167955. https://doi.org/10.1172/JCI167955.
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Clinical Medicine Vaccines

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

Abstract

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.

Authors

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

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Figure 1

Serum antibody responses following mRNA booster vaccinations.

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Serum antibody responses following mRNA booster vaccinations. (A) Schema...
(A) Schematic of the study design and participants’ details. The schematic was made using BioRender. (B and C) Anti–spike-binding IgG (B) and live-virus nAb titers (C) against the ancestral WA.1 strain. Each symbol represents an individual in the 2 plots on the left (n = 55 and n = 13 for the 3- and 4-dose groups, respectively). The black horizontal lines indicate geometric mean titers. The 2 graphs on the right show a summary (geometric mean + SEM) of the antibody responses. (D) nAb titers in groups of participants stratified by exposure to COVID-19. Data shown are the geometric mean for each group + SEM. The statistical difference between groups at each time point was analyzed by the Mann-Whitney U test. F, female; M, male; neg, negative.