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 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 2

nAb breadth following booster vaccinations.

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nAb breadth following booster vaccinations. (A) Live-virus nAb response ...
(A) Live-virus nAb response measured against Omicron BA.1, BA.5, BA.2.75, BA.2.75.2, and BQ.1.1 variants (n = 55 for BA.1, BA.5, and BA.2.75; n = 18 for BA.2.75.2 and BQ.1.1; n = 17 for XBB.1.5). Participants who had the highest titers against the ancestral and Omicron BA.1 variant were selected for this assay. (B) nAb titers against the viruses indicated on the x axis at peak (left panel) and their durability (right panel). Pie charts show the proportion of participants who responded (in orange) versus those who did not (in purple) against each virus. Nonresponders were defined as those who had an IC50 below 30. The numbers inside the graph followed by X indicate the decrease in titers against variants in comparison with the ancestral strain. The fold change was calculated using responders, i.e., those with an IC50 above 30 only. Horizontal dotted lines in A and B indicate the cutoff used to define the responders. (C) nAb titers against the variants indicated on the plots in 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. (D) nAb titers in all SARS-CoV-2–naive individuals. Each symbol represents an individual. Individuals who showed a neutralization titer below 30 against BA.1, BA.5, or BA.2.75 at 6 months were classified as those with a rapid decline (brown). Data points for individuals who showed a less than 4-fold increase in titers against the variants are shown in gray. The rest of the individuals were considered normal responders (green). (E) Live-virus nAb response measured against Omicron variants BA.1, BA.5, and BA.2.75 (n = 13) in participants who received a fourth dose of the mRNA vaccine.