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Antibody avidity maturation favors SARS-CoV-2 convalescents over vaccinated individuals granting breadth in neutralizability and tolerance against variants
Preprint
em Inglês
| medRxiv
| ID: ppmedrxiv-22280078
ABSTRACT
BackgroundThe durability and cross-neutralizability of protective antibodies against evolving SARS-CoV-2 variants are primary concerns in mitigating (re-)exposures. The role of antibody maturation, the process whereby selection of higher avidity antibodies augments host immunity, to determine SARS-CoV-2 neutralizability was investigated. MethodsSera collected from SARS-CoV-2 convalescent individuals at 2- or 10-months after recovery, and BNT162b2 vaccine recipients at 3 or 25 weeks post-vaccination, were analyzed. Anti-spike IgG avidity was measured on a urea-treated ELISA platform. Neutralizing ability of antibodies was assessed by surrogate virus neutralization. Fold change between variant and wild-type antigen neutralizability was calculated to infer breadth of neutralizability. ResultsCompared with early-convalescence, the avidity index of late-convalescent sera was significantly higher (median 37.7 (interquartile range 28.4-45.1) vs. 64.9 (57.5-71.5), p < 0.0001), indicative of progressive antibody maturation extending months beyond acute-phase illness. The urea-resistant, high-avidity fraction of IgG was best predictive of neutralizability (Spearmans r = 0.49 vs. 0.67 for wild-type; 0.18-0.52 vs. 0.48-0.83 for variants). Higher-avidity convalescent sera showed greater cross-neutralizability against SARS-CoV-2 variants (p < 0.001 for Alpha; p < 0.01 for Delta and Omicron). Vaccinees experienced delayed maturation kinetics, translating to limited breadth of neutralizability at week-25 post-vaccination which was only comparable to that of early-convalescence. ConclusionsAvidity maturation grants broader neutralizability that is resilient against emerging SARS-CoV-2 variants. With immunopotentiation through repeat vaccinations becoming a pivotal strategy to accomplish herd immunity, understanding the variable longitudinal evolutions of the two building blocks of hybrid immunity is crucial.
cc_by_nc
Texto completo:
Disponível
Coleções:
Preprints
Base de dados:
medRxiv
Tipo de estudo:
Estudo prognóstico
/
Rct
Idioma:
Inglês
Ano de publicação:
2022
Tipo de documento:
Preprint