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.
ABSTRACT
BackgroundMore people with a history of prior infection are receiving SARS-CoV-2 vaccines. Understanding the magnitude of protectivity granted by hybrid immunity, the combined response of infection- and vaccine-induced immunity, may impact vaccination strategies. MethodsA total of 36 synchronously infected ( prior infection) and, 33 SARS-CoV-2 naive ( naive) individuals participated. Participants provided sera six months after completing a round of BNT162b2 vaccination, to be processed for anti-spike antibody measurements and neutralization assays. The relationships between antibody titer, groups and age were explored. ResultsAnti-spike antibody titers at 6 months post-vaccination were significantly higher, reaching 13- to 17-fold, in the prior infection group. Linear regression models showed that the enhancement in antibody titer attributable to positive infection history increased from 8.9- to 9.4- fold at age 30 to 19- to 32-fold at age 60. Sera from the prior infection group showed higher neutralizing capacity against all six analyzed strains, including the Omicron variant. ConclusionsPrior COVID-19 led to establishing enhanced humoral immunity at 6 months after vaccination. Antibody fold-difference attributed to positive COVID-19 history increased with age, possibly because older individuals are prone to symptomatic infection accompanied by potentiated immune responses. Durable protection of hybrid immunity deserves reflection in vaccination campaigns.
ABSTRACT
We describe the results of testing healthcare workers from a tertiary care hospital in Japan, which had experienced a COVID-19 outbreak during the first peak of the pandemic, for SARS-CoV-2 specific antibody seroconversion. Using two chemiluminescent immunoassays and a confirmatory surrogate virus neutralization test, serological testing unveiled that a surprising 42.2% (27/64) of overlooked COVID-19 diagnoses had occurred when case detection had relied solely on SARS-CoV-2 nucleic acid amplification testing. This undetected portion of the COVID-19 iceberg beneath the surface may potentially have led to silent transmissions and triggered the spread. A questionnaire-based risk assessment was further indicative of exposures to specific aerosol-generating procedures, i.e. non-invasive ventilation, having had conveyed the highest transmission risks and served as the origin of outbreak. Our observations are supportive of a multi-tiered testing approach, including the use of serological diagnostics, in order to accomplish exhaustive case detection along the whole COVID-19 spectrum.
