Antibody Avidity Maturation Following Recovery From Infection or the Booster Vaccination Grants Breadth of SARS-CoV-2 Neutralizing Capacity

• Published in: The Journal of infectious diseases Vol. 227; no. 6; pp. 780 - 787
• Main Authors: Nakagama, Yu, Candray, Katherine, Kaku, Natsuko, Komase, Yuko, Rodriguez-Funes, Maria-Virginia, Dominguez, Rhina, Tsuchida, Tomoya, Kunishima, Hiroyuki, Nagai, Etsuko, Adachi, Eisuke, Ngoyi, Dieudonné Mumba, Yamasue, Mari, Komiya, Kosaku, Hiramatsu, Kazufumi, Uemura, Naoto, Sugiura, Yuki, Yasugi, Mayo, Yamagishi, Yuka, Mikamo, Hiroshige, Shiraishi, Satoshi, Izumo, Takehiro, Nakagama, Sachie, Watanabe, Chihiro, Nitahara, Yuko, Tshibangu-Kabamba, Evariste, Kakeya, Hiroshi, Kido, Yasutoshi
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 28.03.2023
• Subjects: Antibodies, Neutralizing; Antibodies, Viral; Antibody Affinity; Avidity; BNT162 Vaccine; Coronaviruses; COVID-19; COVID-19 Serotherapy; Humans; Humoral immunity; Immunity; Immunoglobulin G; Major; Recovery (Medical); SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus; Urea; Vaccination; Vaccines; avidity; SARS-CoV-2; variants of concern; antibody maturation; neutralization breadth
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiac492

Abstract Background Cross-neutralizing capacity of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is important in mitigating (re-)exposures. Role of antibody maturation, the process whereby selection of higher affinity antibodies augments host immunity, to determine SARS-CoV-2 neutralizing capacity was investigated. Methods Sera from SARS-CoV-2 convalescents at 2, 6, or 10 months postrecovery, and BNT162b2 vaccine recipients at 3 or 25 weeks postvaccination, were analyzed. Anti-spike IgG avidity was measured in urea-treated ELISAs. Neutralizing capacity was assessed by surrogate neutralization assays. Fold change between variant and wild-type neutralization inferred the breadth of neutralizing capacity. Results Compared with early-convalescent, avidity indices of late-convalescent sera were significantly higher (median, 37.7 [interquartile range 28.4–45.1] vs 64.9 [57.5–71.5], P < .0001). Urea-resistant, high-avidity IgG best predicted neutralizing capacity (Spearman r = 0.49 vs 0.67 [wild-type]; 0.18–0.52 vs 0.48–0.83 [variants]). Higher-avidity convalescent sera better cross-neutralized SARS-CoV-2 variants (P < .001 [Alpha]; P < .01 [Delta and Omicron]). Vaccinees only experienced meaningful avidity maturation following the booster dose, exhibiting rather limited cross-neutralizing capacity at week 25. Conclusions Avidity maturation was progressive beyond acute recovery from infection, or became apparent after the booster vaccine dose, granting broader anti-SARS-CoV-2 neutralizing capacity. Understanding the maturation kinetics of the 2 building blocks of anti-SARS-CoV-2 humoral immunity is crucial. Avidity maturation augments host immunity following a natural infection and/or vaccination. For protection against SARS-CoV-2, avidity maturation was progressive beyond acute recovery from infection or became apparent after the booster vaccine dose, and granted broader neutralizing capacity against variant strains.