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. 2024 Dec;46(6):6183-6194.
doi: 10.1007/s11357-024-01215-y. Epub 2024 May 25.

Avidity maturation of humoral response following primary and booster doses of BNT162b2 mRNA vaccine among nursing home residents and healthcare workers

Oladayo A Oyebanji  1 , Nicholas Sundheimer  1 , Vaishnavi Ragavapuram  2 , Brigid M Wilson  3 , Yasin Abul  4   5 , Stefan Gravenstein  4   5   6 , Jürgen Bosch  2 , Christopher L King  2 , David H Canaday  7   8
Affiliations

Avidity maturation of humoral response following primary and booster doses of BNT162b2 mRNA vaccine among nursing home residents and healthcare workers

Oladayo A Oyebanji et al. Geroscience. 2024 Dec.

Abstract

Infections, despite vaccination, can be clinically consequential for frail nursing home residents (NHR). Poor vaccine-induced antibody quality may add risk for such subsequent infections and more severe disease. We assessed antibody binding avidity, as a surrogate for antibody quality, among NHR and healthcare workers (HCW). We longitudinally sampled 112 NHR and 52 HCWs who received the BNT162b2 mRNA vaccine after each dose up to the Wuhan-BA.4/5-based Omicron bivalent boosters. We quantified anti-spike, anti-receptor binding domain (RBD), and avidity levels to the ancestral Wuhan, Delta, and Omicron BA.1 & 4/5 strains. The primary vaccination series produced substantial anti-spike and RBD levels which were low in avidity against all strains tested. Antibody avidity progressively increased in the 6-8 months that followed. Avidity significantly increased after the 1st booster but not for subsequent boosters. This study underscores the importance of booster vaccination among NHR and HCWs. The 1st booster dose increases avidity, increasing vaccine-induced functional antibody. The higher cross-reactivity of higher avidity antibodies to other SARS-CoV-2 strains should translate to better protection from ever-evolving strains. Higher avidities may help explain how the vaccine's protective effects persist despite waning antibody titers after each vaccine dose.

Keywords: Affinity maturation; Avidity; BNT162b2 mRNA vaccine; Bivalent boosters; COVID-19; Healthcare workers; Nursing home residents; Omicron.

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Conflict of interest statement

Stefan Gravenstein (S. G.) and David H. Canaday (D. H. C.) are recipients of investigator-initiated grants to their universities from Pfizer to study pneumococcal vaccines, Moderna to study respiratory infection surveillance, and Sanofi Pasteur and Seqirus to study influenza vaccines, and S.G. from Genentech on influenza antivirals. S. G. also receives consulting fees from GlaxoSmithKline, Icosavax, Janssen, Merck, Moderna, Novavax, Pfizer, Reviral, Sanofi, Seqirus, and Vaxart, and has received fees for speaking for Janssen, Moderna, Sanofi, and Seqirus.

Figures

Fig. 1
Fig. 1
Timeline of blood sampling from participants. Serum samples were collected from participants at different time points after BNT162b2 mRNA vaccination. Doses 1 and 2 are the 1st and 2nd doses, respectively, given 3 weeks apart. Doses 3 and 4 are the 1st and 2nd monovalent booster doses, given at least 6 months after the previous dose. Dose 5 is a Wuhan-Omicron BA.4/5-containing bivalent booster dose. While many of our participants did not receive the 2nd monovalent booster (Dose 4), those who did, got the bivalent booster within 4-6 months
Fig. 2
Fig. 2
Spike Antibody titers over time (Wuhan & BA.1) - nursing home residents & healthcare workers. The figure shows the kinetics of anti-spike antibodies against the Wuhan and Omicron BA.1 strains across different time points among nursing home residents and healthcare workers. Wuhan anti-Spike is measured in BAU/ml while BA.1 is measured in AU/ml. Boxplots show medians (middle line), and third and first quartiles (boxes), while the whiskers display the minimum and maximum values. Post-vaccination sera were taken 2-4 weeks after each dose while M6 and M9 sera were taken 6-8 months and 7-10 months later. Blue: Naive subjects, Red: Prior subjects. BV: Wuhan-Omicron BA.5 Bivalent booster
Fig. 3
Fig. 3
Avidity of anti-spike IgG against Wuhan and Omicron BA.1 strains over time. The figure shows the relative avidity of anti-spike antibodies against the Wuhan and Omicron BA.1 strains across different time points among nursing home residents and healthcare workers measured using 6M urea as a chaotropic reagent. Antibody avidity was expressed as avidity index in %. Boxplots show medians (middle line) and third and first quartiles (boxes), while the whiskers display the minimum and maximum values. Post-vaccination sera were taken 2-4 weeks after each dose, while M6 and M9 sera were taken 6-8 months and 7-10 months later. Blue: Naive subjects (no prior infection), Red: Prior subjects (previously infected). BV: Wuhan-Omicron BA.5 Bivalent booster
Fig. 4
Fig. 4
Spike avidity determined by 2.1 M NH4SCN across the booster doses. Relative avidity of anti-spike antibodies against the Wuhan, Omicron BA.1, and BA.5 strains across different time points among nursing home residents and healthcare workers was measured using ammonium isothiocyanate (NH4SCN). Antibody avidity is expressed as avidity index in %. Boxplots show medians (middle line), and third and first quartiles (boxes), while the whiskers display the minimum and maximum values. Post-vaccination sera were taken 2-4 weeks after each booster dose, while M6 post-BV serum was obtained 6-8 months after the BV Booster dose. Blue: Naive subjects (no prior infection), Red: Prior subjects (previously infected). BV: Wuhan-Omicron BA.5 Bivalent booster
Fig 5
Fig 5
Relative anti-S and anti-RBD avidity index by strain, and prior infection status among nursing home residents. This figure, color-coded according to avidity level, presents the median avidity values (with interquartile ranges) measured using 6M Urea. Postvaccination sera were taken 2-4 weeks after each dose while M6 and M9 sera were taken 6-8 months and 7-10 months later. Avidity is expressed as avidity index in % and assessed based on the following ranges: <30% (low avidity), 30-59% (intermediate avidity), 60-75% (high avidity), and >75% (very high avidity). Naive subjects: no prior infection), Prior subjects: previously infected. RBD: Receptor-Binding Domain
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References

    1. Nanduri S, Pilishvili T, Derado G, et al. Effectiveness of Pfizer-BioNTech and Moderna Vaccines in Preventing SARS-CoV-2 Infection Among Nursing Home Residents Before and During Widespread Circulation of the SARS-CoV-2 B.1.617.2 (Delta) Variant — National Healthcare Safety Network, March 1–August 1, 2021. MMWR Morb Mortal Wkly Rep. 2021;70:1163–6. 10.15585/mmwr.mm7034e3. - PMC - PubMed
    1. Nilsson L, Andersson C, Kastbom L, Sjödahl R. Association between vaccination and preventive routines on COVID-19-related mortality in nursing home facilities: a population-based systematic retrospective chart review. Prim Health Care Res Dev. 2022;18(23): e75. 10.1017/S1463423622000640. - PMC - PubMed
    1. Canaday DH, Oyebanji OA, Keresztesy D, et al. Significant reduction in vaccine-induced antibody levels and neutralization activity among healthcare workers and nursing home residents 6 months following coronavirus disease 2019 BNT162b2 mRNA vaccination. Clin Infect Dis. 2022;75(1):e884–7. 10.1093/cid/ciab963. - PMC - PubMed
    1. Menegale F, Manica M, Zardini A, et al. Evaluation of Waning of SARS-CoV-2 Vaccine-Induced Immunity: A Systematic Review and Meta-analysis. JAMA Netw Open. 2023;6(5): e2310650. 10.1001/jamanetworkopen.2023.10650. - PMC - PubMed
    1. Lustig Y, Gonen T, Meltzer L, et al. Superior immunogenicity and effectiveness of the third compared to the second BNT162b2 vaccine dose. Nat Immunol. 2022. 10.1038/s41590-022-01212-3. - PubMed

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