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

• Published in: The Journal of clinical investigation Vol. 133; no. 10; pp. 1 - 10
• Main Authors: Arunachalam, Prabhu S., Lai, Lilin, Samaha, Hady, Feng, Yupeng, Hu, Mengyun, Hui, Harold Sai-yin, Wali, Bushra, Ellis, Madison, Davis-Gardner, Meredith E., Huerta, Christopher, Bechnak, Kareem, Bechnak, Sarah, Lee, Matthew, Litvack, Matthew B., Losada, Cecilia, Grifoni, Alba, Sette, Alessandro, Zarnitsyna, Veronika I., Rouphael, Nadine, Suthar, Mehul S., Pulendran, Bali
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 15.05.2023
• Subjects: Adult; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; Biomedical research; Clinical Medicine; COVID-19; COVID-19 - prevention & control; COVID-19 Vaccines; Estimates; Health aspects; Humans; Immune response; Immunity; Immunological memory; Immunology; Infections; Lymphocytes T; Memory cells; mRNA; mRNA vaccines; Physiological aspects; RNA, Messenger; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Vaccination; Vaccines; United States; Adaptive immunity; Vaccines
• ISSN: 1558-8238; 0021-9738; 1558-8238
• DOI: 10.1172/JCI167955

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.