Immunodominant B cell epitope in a hotspot mutation site and mechanism of immune escape for SARS-CoV-2

Oliveira, Jamille R; Machado, Rafael; Magawa, Jhosiene Y.; Daher, Isabela Pazotti; Urbanski, Alysson H.; Schmitz, Gabriela Jh; Silva, Roberto Carlos V; Durigon, Edison L.; Boscardin, Sílvia Beatriz; Rosa, Daniela Santoro; Schechtman, Deborah; Nakaya, Helder I.; Cunha‐Neto, Edécio; Gadermaier, Gabriele; Coelho, Verônica; Santos, Keity Souza; Kalil, Jorge

doi:10.1101/2021.03.11.21253399

Cited by 6 publications

(7 citation statements)

References 23 publications

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“…These mutations, located at the interfaces of the RBD-ACE2/antibody complexes, have been shown to increase Spike binding to ACE2 and decrease its recognition by neutralizing antibodies (Nab) (28,(43)(44)(45), leading to the enhanced infection efficacy and transmissibility for the variants. Intriguingly, the same amino acid changes have been shown to alter the corresponding epitopes targeted by neutralizing antibodies (28), thereby providing a potential mechanism of immune escape by reducing or disabling antibody-mediated neutralization (43,(46)(47)(48). Besides the RBD, a P681H mutation located in the S1/S2 linker region of the Spike has been detected in multiple VOC (31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

Epitope-specific antibody responses differentiate COVID-19 outcomes and variants of concern

Voss¹,

Esmail²,

Liu³

et al. 2021

JCI Insight

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BACKGROUND. The role of humoral immunity in the coronavirus disease 2019 (COVID-19) is not fully understood owing, in large part, to the complexity of antibodies produced in response to the SARS-CoV-2 infection. There is a pressing need for serology tests to assess patient-specific antibody response and predict clinical outcome. METHODS. Using SARS-CoV-2 proteome and peptide microarrays, we screened 146 COVID-19 patients plasma samples to identify antigens and epitopes. This enabled us to develop a master epitope array and an epitope-specific agglutination assay to gauge antibody responses systematically and with high resolution. RESULTS. We identified linear epitopes from the Spike (S) and Nucleocapsid (N) protein and showed that the epitopes enabled higher resolution antibody profiling than the S or N protein antigen. Specifically, we found that antibody responses to the S(811-825), S(881-895) and N(156-170) epitopes negatively or positively correlated with clinical severity or patient survival. Moreover, we found that the P681H and S235F mutations associated with the coronavirus variant of concern B.1.1.7 altered the specificity of the corresponding epitopes. CONCLUSIONS. Epitope-resolved antibody testing not only affords a high-resolution alternativeto conventional immunoassays to delineate the complex humoral immunity to SARS-CoV-2 and differentiate between neutralizing and non-neutralizing antibodies, it may potentially be used to predict clinical outcome. The epitope peptides can be readily modified to detect antibodies against variants of concern (VOC) in both the peptide array and latex agglutination formats.

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Section: Discussionmentioning

confidence: 99%

Epitope-specific antibody responses differentiate COVID-19 outcomes and variants of concern

Voss¹,

Esmail²,

Liu³

et al. 2021

JCI Insight

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“…Enzyme-linked immunosorbent assay (ELISA) was performed using 96-well high- binding half-area polystyrene plates coated overnight at 4°C with 4 μg/ml of Spike protein, 2 μg/ml Nucleocapsid protein (NP) (Kindly provided by Dr. Ricardo Gazzinelli, UFMG, Brazil) or 0.8 μg/ml of the RBD domain from SARS-CoV-2 were all expressed in HEK293T cells ( 12 ). In short, 50 µl of diluted sera (1:100) were incubated at 37°C for 45 min.…”

Section: Methodsmentioning

confidence: 99%

Reduced T Cell and Antibody Responses to Inactivated Coronavirus Vaccine Among Individuals Above 55 Years Old

et al. 2022

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CoronaVac is an inactivated SARS-CoV-2 vaccine that has been rolled out in several low and middle-income countries including Brazil, where it was the mainstay of the first wave of immunization of healthcare workers and the elderly population. We aimed to assess the T cell and antibody responses of vaccinated individuals as compared to convalescent patients. We detected IgG against SARS-CoV-2 antigens, neutralizing antibodies against the reference Wuhan SARS-CoV-2 strain and used SARS-CoV-2 peptides to detect IFN-g and IL-2 specific T cell responses in a group of CoronaVac vaccinated individuals (N = 101) and convalescent (N = 72) individuals. The frequency among vaccinated individuals, of whom 96% displayed T cell and/or antibody responses to SARS-CoV-2, is comparable to 98.5% responses of convalescent individuals. We observed that among vaccinated individuals, men and individuals 55 years or older developed significantly lower anti-RBD, anti-NP and neutralization titers against the Wuhan strain and antigen-induced IL-2 production by T cells. Neutralizing antibody responses for Gamma variant were even lower than for the Wuhan strain. Even though some studies indicated CoronaVac helped reduce mortality among elderly people, considering the appearance of novel variants of concern, CoronaVac vaccinated individuals above 55 years old are likely to benefit from a heterologous third dose/booster vaccine to increase immune response and likely protection.

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“…This interaction seems stronger than the binding between ACE2 and the original main site located at position 501 ( Ferrareze et al ., 2021 ; Nelson et al ., 2021 ). Other studies have shown that 484K reduces neutralization by polyclonal antibodies ( Greaney et al ., 2021 ; Oliveira et al ., 2021 ). Oliveira et al .…”

Section: Discussionmentioning

confidence: 99%

Evolutionary history of the SARS-CoV-2 Gamma variant of concern (P.1): a perfect storm

et al. 2022

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Our goal was to describe in more detail the evolutionary history of Gamma and two derived lineages (P.1.1 and P.1.2), which are part of the arms race that SARS-CoV-2 wages with its host. A total of 4,977 sequences of the Gamma strain of SARS-CoV-2 from Brazil were analyzed. We detected 194 sites under positive selection in 12 genes/ORFs: Spike, N, M, E, ORF1a, ORF1b, ORF3, ORF6, ORF7a, ORF7b, ORF8, and ORF10 . Some diagnostic sites for Gamma lacked a signature of positive selection in our study, but these were not fixed, apparently escaping the action of purifying selection. Our network analyses revealed branches leading to expanding haplotypes with sites under selection only detected when P.1.1 and P.1.2 were considered. The P.1.2 exclusive haplotype H_5 originated from a non-synonymous mutational step (H3509Y) in H_1 of ORF1a. The selected allele, 3509Y, represents an adaptive novelty involving ORF1a of P.1. Finally, we discuss how phenomena such as epistasis and antagonistic pleiotropy could limit the emergence of new alleles (and combinations thereof) in SARS-COV-2 lineages, maintaining infectivity in humans, while providing rapid response capabilities to face the arms race triggered by host immuneresponses.

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Immunodominant B cell epitope in a hotspot mutation site and mechanism of immune escape for SARS-CoV-2

Cited by 6 publications

References 23 publications

Epitope-specific antibody responses differentiate COVID-19 outcomes and variants of concern

Epitope-specific antibody responses differentiate COVID-19 outcomes and variants of concern

Reduced T Cell and Antibody Responses to Inactivated Coronavirus Vaccine Among Individuals Above 55 Years Old

Evolutionary history of the SARS-CoV-2 Gamma variant of concern (P.1): a perfect storm

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