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

• Type of Material: Article
• Authors: Prabhu Arunachalam, Stanford University; Lilin Lai, Emory University; Hady Samaha, Emory University; Yupeng Feng, Stanford University; Mengyun Hu, Stanford University; Harold Sai-yin Hui, Stanford University; Bushra Wali, Emory University; Madison Ellis, Emory University; Meredith E. Davis-Gardner, Emory University; Christopher Huerta, Emory University; Kareem Bechnak, Emory University; Sarah Bechnak, Emory University; Matthew Lee, Emory University; Matthew B. Litvack, Emory University; Cecilia Losada, Emory University; Alba Grifoni, La Jolla Institute for Allergy and Immunology; Alessandro Sette, La Jolla Institute for Allergy and Immunology; Veronika Zarnitsyna, Emory University; Nadine Rouphael, Emory University; Mehul Suthar, Emory University; Bali Pulendran, Emory University
• Language: English
• Date: 2023-05-15
• Publisher: JCI
• Publication Version: Final Published Version
• Copyright Statement: © 2023 Arunachalam et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1172/JCI167955
• Title of Journal or Parent Work: The Journal of clinical investigation
• Volume: 133
• Issue: 10
• Grant/Funding Information: This study was supported by NIH grants U19 AI057266 and U19 AI167903; the Bill and Melinda Gates Foundation; Open Philanthropy; Violetta L. Horton and Soffer Endowments; and by contributions from an anonymous donor (to BP). This work was supported in part by NIH grants P51OD011132, 1U54CA260563, and HHSN272201400004C; the National Institute of Allergy and Infectious Diseases, NIH (NIAID/NIH) Centers of Excellence for Influenza Research and Response (CEIRR) (contract no. 75N93021C00017, to Emory University); and a Woodruff Health Sciences Center 2020 COVID-19 CURE Award (to MSS). Additional NIH support was provided under contract no. 75N93021C00016 (to AG and AS) and U01 AI141995 and U19 AI118626 (to AS).
• Keywords: Vaccination; COVID-19 Vaccines; Adaptive immunity; RNA, Messenger; Adult; Antibodies, Viral; SARS-CoV-2; Immunity; Antibodies, Neutralizing; Vaccines; COVID-19; Humans
• Research Categories: Health Sciences, Immunology; Biology, Virology

Abstract

BackgroundMaintaining durable immunity following vaccination represents a major challenge, but whether mRNA booster vaccination improves durability is unknown.MethodsWe 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.ResultsThe 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.ConclusionThe durability of serum antibody responses improves only marginally following booster immunizations with the Pfizer-BioNTech or Moderna mRNA vaccines.