Characterization of neutralizing versus binding antibodies and memory B cells in COVID-19 recovered individuals from India

Nayak, Kaustuv; Gottimukkala, Kamalvishnu; Kumar, Sanjeev; Reddy, Elluri Seetharami; Edara, Venkata Viswanadh; Kauffman, Robert C.; Floyd, Katharine; Mantus, Grace; Savargaonkar, Deepali; Goel, Pawan Kumar; Arora, Satyam; Rahi, Manju; Davis, Carl W.; Linderman, Susanne L.; Wrammert, Jens; Suthar, Mehul S.; Ahmed, Rafi; Sharma, Amit; Murali‐Krishna, Kaja; Chandele, Anmol

doi:10.1016/j.virol.2021.02.002

Cited by 26 publications

(25 citation statements)

References 57 publications

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“…Furthermore, some studies have found that the IgA isotype contributes to virus neutralization to a greater extent compared with IgG [ 36 ]. In agreement with our results, recent work from India, a heavily impacted country by the pandemic, found that RBD-specific IgG, but not IgA or IgM titers, correlated with neutralizing antibody titers and RBD-specific memory B cell frequencies [ 37 ]. In our work, we found that IgG1 was the predominant isotype, while the IgA response was more limited.…”

Section: Discussionsupporting

confidence: 93%

Function Is More Reliable than Quantity to Follow Up the Humoral Response to the Receptor-Binding Domain of SARS-CoV-2-Spike Protein after Natural Infection or COVID-19 Vaccination

Sariol

Pantoja

Serrano-Collazo

et al. 2021

Viruses

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Both the SARS-CoV-2 pandemic and emergence of variants of concern have highlighted the need for functional antibody assays to monitor the humoral response over time. Antibodies directed against the spike (S) protein of SARS-CoV-2 are an important component of the neutralizing antibody response. In this work, we report that in a subset of patients—despite a decline in total S-specific antibodies—neutralizing antibody titers remain at a similar level for an average of 98 days in longitudinal sampling of a cohort of 59 Hispanic/Latino patients exposed to SARS-CoV-2. Our data suggest that 100% of seroconverting patients make detectable neutralizing antibody responses which can be quantified by a surrogate viral neutralization test. Examination of sera from ten out of the 59 subjects which received mRNA-based vaccination revealed that both IgG titers and neutralizing activity of sera were higher after vaccination compared to a cohort of 21 SARS-CoV-2 naïve subjects. One dose was sufficient for the induction of a neutralizing antibody, but two doses were necessary to reach 100% surrogate virus neutralization in subjects irrespective of previous SARS-CoV-2 natural infection status. Like the pattern observed after natural infection, the total anti-S antibodies titers declined after the second vaccine dose; however, neutralizing activity remained relatively constant for more than 80 days after the first vaccine dose. Furthermore, our data indicates that—compared with mRNA vaccination—natural infection induces a more robust humoral immune response in unexposed subjects. This work is an important contribution to understanding the natural immune response to the novel coronavirus in a population severely impacted by SARS-CoV-2. Furthermore, by comparing the dynamics of the immune response after the natural infection vs. the vaccination, these findings suggest that functional neutralizing antibody tests are more relevant indicators than the presence or absence of binding antibodies.

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Section: Discussionsupporting

confidence: 93%

Function Is More Reliable than Quantity to Follow Up the Humoral Response to the Receptor-Binding Domain of SARS-CoV-2-Spike Protein after Natural Infection or COVID-19 Vaccination

Sariol

Pantoja

Serrano-Collazo

et al. 2021

Viruses

View full text Add to dashboard Cite

show abstract

“…It is well known that antibody levels correlate with protection against many viruses including SARS-CoV-2, and recent data suggest that high neutralizing titers are particularly important for protection against the novel SARS-CoV-2 causing the COVID-19 pandemic. 12 , 13 In the current study we used the Euroimmune ELISA assay to quantify SARS-CoV-2 antibody level as it was reported to highly correlate with the neutralizing antibody assay. 14 …”

Section: Discussionmentioning

confidence: 99%

Humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies

Achiron

Mandel

Dreyer-Alster

et al. 2021

Ther Adv Neurol Disord

311

326

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Background and Aims: The National Multiple Sclerosis Society and other expert organizations recommended that all patients with multiple sclerosis (MS) should be vaccinated against COVID-19. However, the effect of disease-modifying therapies (DMTs) on the efficacy to mount an appropriate immune response is unknown. We aimed to characterize humoral immunity in mRNA-COVID-19 MS vaccinees treated with high-efficacy DMTs. Methods: We measured SARS-CoV-2 IgG response using anti-spike protein-based serology (EUROIMMUN) in 125 MS patients vaccinated with BNT162b2-COVID-19 vaccine 1 month after the second dose. Patients were either untreated or under treatment with fingolimod, cladribine, or ocrelizumab. A group of healthy subjects similarly vaccinated served as control. The percent of subjects that developed protective antibodies, the titer, and the time from the last dosing were evaluated. Results: Protective humoral immunity of 97.9%, 100%, 100%, 22.7%, and 3.8%, was observed in COVID-19 vaccinated healthy subjects ( N = 47), untreated MS patients ( N = 32), and MS patients treated with cladribine ( N = 23), ocrelizumab ( N = 44), and fingolimod ( N = 26), respectively. SARS-CoV-2 IgG antibody titer was high in healthy subjects, untreated MS patients, and MS patients under cladribine treatment, within 29.5–55 days after the second vaccine dose. Only 22.7% of patients treated with ocrelizumab developed humoral IgG response irrespective to normal absolute lymphocyte count. Most fingolimod-treated MS patients had very low lymphocyte count and failed to develop SARS-COV-2 antibodies. Age, disease duration, and time from the last dosing did not affect humoral response to COVID-19 vaccination. Conclusions: Cladribine treatment does not impair humoral response to COVID-19 vaccination. We recommend postponing ocrelizumab treatment in MS patients willing to be vaccinated as a protective humoral response can be expected only in some. We do not recommend vaccinating MS patients treated with fingolimod as a protective humoral response is not expected.

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“…It should be noted that most S-protein-binding antibodies, and even most RBD-binding antibodies, do not have the ability to neutralize the virus [ 9 , 34 ]. Total anti-RBD or anti-S antibody titer may more or less correlate with nAb levels [ 35 ] but cannot replace VNT or sVNT results.…”

Section: Discussionmentioning

confidence: 99%

Fast and Accurate Surrogate Virus Neutralization Test Based on Antibody-Mediated Blocking of the Interaction of ACE2 and SARS-CoV-2 Spike Protein RBD

et al. 2022

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The humoral response to the SARS-CoV-2 S protein determines the development of protective immunity against this infection. The standard neutralizing antibodies detection method is a live virus neutralization test. It can be replaced with an ELISA-based surrogate virus neutralization test (sVNT), measuring the ability of serum antibodies to inhibit complex formation between the receptor-binding domain (RBD) of the S protein and the cellular ACE2 receptor. There are conflicting research data on the sVNT methodology and the reliability of its results. We show that the performance of sVNT dramatically improves when the intact RBD from the Wuhan-Hu-1 virus variant is used as the plate coating reagent, and the HRP-conjugated soluble ACE2 is used as the detection reagent. This design omits the pre-incubation step in separate tubes or separate microplate and allows the simple quantification of the results using the linear regression, utilizing only 3–4 test sample dilutions. When this sVNT was performed for 73 convalescent plasma samples, its results showed a very strong correlation with VNT (Spearman’s Rho 0.83). For the RBD, bearing three amino acid substitutions and corresponding to the SARS-CoV-2 beta variant, the inhibitory strength was diminished for 18 out of 20 randomly chosen serum samples, and the magnitude of this decrease was not similar to the change in overall anti-RBD IgG level. The sVNT assay design with the ACE2-HRP is preferable over the assay with the RBD-HRP reagent and is suitable for mass screening of neutralizing antibodies titers.

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Characterization of neutralizing versus binding antibodies and memory B cells in COVID-19 recovered individuals from India

Cited by 26 publications

References 57 publications

Function Is More Reliable than Quantity to Follow Up the Humoral Response to the Receptor-Binding Domain of SARS-CoV-2-Spike Protein after Natural Infection or COVID-19 Vaccination

Function Is More Reliable than Quantity to Follow Up the Humoral Response to the Receptor-Binding Domain of SARS-CoV-2-Spike Protein after Natural Infection or COVID-19 Vaccination

Humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies

Fast and Accurate Surrogate Virus Neutralization Test Based on Antibody-Mediated Blocking of the Interaction of ACE2 and SARS-CoV-2 Spike Protein RBD

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