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 Research and Public Health

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 3

Memory B cell responses to the booster vaccination.

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Memory B cell responses to the booster vaccination. (A) Representative f...
(A) Representative flow cytometry profile showing the gating strategy to define spike-specific B cell frequencies (gated as live CD20+IgD–IgM–spike+ RBD+/– cells. (B) Frequency of WA.1 spike–specific (top panel) or RBD-specific (bottom panel) memory B cells relative to CD20+IgD–IgM– B cells. Each symbol represents an individual (n = 28, after the third dose; n = 13, after the fourth dose). The statistical differences between time points were determined using the Wilcoxon matched-pairs, signed-rank test. The 2 graphs on the right show a summary of the responses (geometric mean + SEM). The statistical difference between the groups was determined using the Mann-Whitney U test.