RBD-Based ELISA and Luminex Predict Anti-SARS-CoV-2 Surrogate-Neutralizing Activity in Two Longitudinal Cohorts of German and Spanish Health Care Workers

Aguilar, Ruth; Li, Xue; Crowell, Claudia S.; Burrell, Teresa; Vidal, Marta; Rubio, Rocío; Jiménez, Alfons; Hernández-Luis, Pablo; Hofmann, Dieter; Mijočević, Hrvoje; Jeske, Samuel; Christa, Catharina; D’Ippolito, Elvira; Lingor, Paul; Knolle, Percy; Roggendorf, Hedwig; Priller, Alina; Yazici, Sarah; Carolis, Carlo; Mayor, Alfredo; Schreiner, Patrik; Poppert, Holger; Beyer, H; Schambeck, Sophia; Izquierdo, Luís; Tortajada, Marta; Angulo, Ana; Soutschek, Erwin; Engel, Pablo; García‐Basteiro, Alberto L.; Busch, Dirk H.; Moncunill, Gemma; Protzer, Ulrike; Dobaño, Carlota; Gerhard, Markus

doi:10.1128/spectrum.03165-22

Cited by 2 publications

(4 citation statements)

References 60 publications

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“…In addition, the bead-based multiplex assay is comparable to commercial ELISA/CLIA tests in antibody detection. This is in accordance with previous publications [32,33]. In fact, the bead-based assay performed better in detecting the RBD antibody in our examination and shows up to 22% more positive results compared to the ELISA (Figure 4b).…”

Section: Discussionsupporting

confidence: 93%

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Potential of a Bead-Based Multiplex Assay for SARS-CoV-2 Antibody Detection

Rottmayer,

Schwarze,

Jassoy

et al. 2024

Biology

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Serological assays for SARS-CoV-2 play a pivotal role in the definition of whether patients are infected, the understanding of viral epidemiology, the screening of convalescent sera for therapeutic and prophylactic purposes, and in obtaining a better understanding of the immune response towards the virus. The aim of this study was to investigate the performance of a bead-based multiplex assay. This assay allowed for the simultaneous testing of IgG antibodies against SARS-CoV-2 spike, S1, S2, RBD, and nucleocapsid moieties and S1 of seasonal coronaviruses hCoV-22E, hCoV-HKU1, hCoV-NL63, and hCoV-OC43, as well as MERS and SARS-CoV. We compared the bead-based multiplex assay with commercial ELISA tests. We tested the sera of 27 SARS-CoV-2 PCR-positive individuals who were previously tested with different ELISA assays. Additionally, we investigated the reproducibility of the results by means of multiple testing of the same sera. Finally, the results were correlated with neutralising assays. In summary, the concordance of the qualitative results ranged between 78% and 96% depending on the ELISA assay and the specific antigen. Repeated freezing–thawing cycles resulted in reduced mean fluorescence intensity, while the storage period had no influence in this respect. In our test cohort, we detected up to 36% of sera positive for the development of neutralising antibodies, which is in concordance with the bead-based multiplex and IgG ELISA.

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Section: Discussionsupporting

confidence: 93%

“…This suggests that over 60% of individuals developed no neutralising antibodies. The literature reports that 80-90% of people develop neutralising antibodies [33][34][35]. Neutralising antibodies peak during convalescence and then remain relatively stable for up to 15 months [35].…”

Section: Discussionmentioning

confidence: 99%

Potential of a Bead-Based Multiplex Assay for SARS-CoV-2 Antibody Detection

Rottmayer,

Schwarze,

Jassoy

et al. 2024

Biology

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“…As RBD is the major target for neutralization antibodies (nAbs), antibody levels to this fragment of spike protein are a good alternative to predict serum neutralization function, especially in resource-constrained countries like Ethiopia ( 16 ). We specifically used an in-house anti-RBD IgG ELISA to assess natural infection- and BNT vaccine-induced antibody responses in schoolchildren in Hawassa, Ethiopia.…”

Section: Discussionmentioning

confidence: 99%

“…Although COVID-19 vaccines have become more available to Africans, including children through the African Vaccine Acquisition Task Team of the African Union and the World Health Organization (WHO)-led COVAX consortium ( 14 ), there is limited or no local evidence regarding vaccine-induced immune response among pediatric populations in Africa, particularly in Ethiopia. The generation of virus-specific antibodies which neutralize or block infectivity is the most consistent correlate of protective immunity for multiple infections and vaccines ( 6 , 15 , 16 ). Given the role of SARS-CoV-2 receptor binding domain (RBD) in SARS-CoV-2 entry to host cells via angiotensin-converting enzyme 2 (ACE2) and anti-RBD antibodies’ role in blocking virus binding to host receptors, measuring the level of anti-RBD IgG antibodies is considered as a proxy marker for virus neutralization, and indirect indication for the effectiveness of a vaccine against SARS-CoV-2 ( 17 , 18 ).…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Infection-and mRNA Vaccine-induced Humoral Immunity among Schoolchildren in Hawassa, Ethiopia

et al. 2023

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BackgroundWith the persisting low vaccination intake, particularly in children of low-and middle-income countries (LMICs), seroepidemiological studies are urgently needed to guide and tailor COVID-19 pandemic response efforts in schools and to put mitigation strategies in place for a future post-pandemic resurgence. However, there is limited data on SARS-CoV-2 infection-induced and vaccine-induced humoral immunity in schoolchildren in LMICs, including Ethiopia.MethodsAs the spike receptor binding domain (RBD) is the major target for neutralization antibodies and useful to predict the correlates of protection, we used an in-house anti-RBD IgG ELISA to assess and compare infection-induced antibody response at two-time points and BNT162b2 (BNT) vaccine-induced antibody response at a one-time point in schoolchildren in Hawassa, Ethiopia. In addition, we measured and compared the levels of binding IgA antibodies to spike RBD of SARS-CoV-2 Wild type, Delta, and Omicron variants in a small subset of unvaccinated and BNT-vaccinated schoolchildren.ResultsWhen we compare SARS-CoV-2 infection-induced seroprevalences among unvaccinated school children (7-19 years) at the two blood sampling points with a 5-month interval, we observed an over 10% increase, from 51.8% (219/419) in the first week of December 2021 (post-Delta wave) to 67.4% (60/89) by the end of May 2022 (post-Omicron wave). Additionally, we found a significant correlation (p = 0.001) between anti-RBD IgG seropositivity and a history of having COVID-19-like symptoms. Compared to the levels of SARS-CoV-2 infection-induced anti-RBD IgG antibodies before vaccination, higher levels of BNT vaccine-induced anti-RBD IgG antibodies were observed even in SARS-CoV-2 infection-naïve schoolchildren of all age groups (p = 0.0001). Importantly, one dose of the BNT vaccine was shown to be adequate to elicit a strong antibody response in schoolchildren with pre-existing anti-RBD IgG antibodies comparable to that of SARS-CoV-2 infection-naive schoolchildren receiving two doses of BNT vaccine, suggesting a single dose administration of the BNT vaccine could be considered for schoolchildren who had prior SARS-CoV-2 infection when a shortage of vaccine supply is a limiting factor to administer two doses irrespective of their serostatus. Despite the small sample size of study participants, the BNT vaccine is shown to be immunogenic and safe for schoolchildren. Irrespective of schoolchildren’s vaccination status, we observed a similar pattern of significantly higher levels of IgA antibodies to Delta-RBD than to Omicron-RBD (p < 0.001) in a randomly selected subset of schoolchildren, yet comparable to Wuhan-RBD, suggesting these schoolchildren were more likely to have had SARS-CoV-2 infection with Delta variant. Additionally, we noted a broader IgA antibody reactivity to SARS-CoV-2 variants in vaccinated schoolchildren with prior SARS-CoV-2 infection, supporting the superiority of hybrid immunity.ConclusionOur serological data indicate a significant increase in SARS-CoV-2 seroprevalence in children at a post-Omicron five-month follow-up compared to a post-Delta enrolment. Despite the small sample size of study participants, the BNT vaccine is shown to be immunogenic and safe for schoolchildren. Hybrid immunity would likely provide a broader humoral immunity against Wuhan strain, Delta, and Omicron variants than natural infection or vaccination alone does. However, future longitudinal cohort studies in SARS-CoV-2-naïve and COVID-19-recovered schoolchildren receiving the BNT vaccine are needed for a better understanding of the kinetics, breadth, and durability of BNT vaccine-induced multivariant-cross reactive immunity.

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RBD-Based ELISA and Luminex Predict Anti-SARS-CoV-2 Surrogate-Neutralizing Activity in Two Longitudinal Cohorts of German and Spanish Health Care Workers

Abstract: Neutralizing antibody titers are the best correlate of protection against SARS-CoV-2. However, current tests to measure plasma or serum neutralizing activity do not allow high-throughput screening at the population level.

Cited by 2 publications

References 60 publications

Potential of a Bead-Based Multiplex Assay for SARS-CoV-2 Antibody Detection

Potential of a Bead-Based Multiplex Assay for SARS-CoV-2 Antibody Detection

SARS-CoV-2 Infection-and mRNA Vaccine-induced Humoral Immunity among Schoolchildren in Hawassa, Ethiopia

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