High-Resolution Linear Epitope Mapping of the Receptor Binding Domain of SARS-CoV-2 Spike Protein in COVID-19 mRNA Vaccine Recipients

Nitahara, Yuko; Nakagama, Yu; Kaku, Natsuko; Candray, Katherine; Michimuko, Yu; Tshibangu‐Kabamba, Evariste; Kaneko, Akira; Yamamoto, Hiromasa; Mizobata, Yasumitsu; Kakeya, Hiroshi; Yasugi, Mayo; Kido, Yasutoshi

doi:10.1128/spectrum.00965-21

Cited by 18 publications

(16 citation statements)

References 41 publications

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“…), but they are not as sensitive to partially altered structures within RBD-J. In the future, it will be of interest to explore if other mechanisms may help explain some of these in vitro vs in vivo results including the possible role of (1) linear neutralization epitopes within the receptor-binding motif (RBM) which may be exposed upon structural alterations of RBD-J during stress and may directly block binding of RBD-J to ACE2, 75 , 76 and (2) conformational epitopes outside of the ACE2 binding region that may remain unperturbed in structurally altered RBD-J protein after storage, and thus could elicit antibodies that may sterically hinder ACE2-RBD-J interactions and neutralize the pseudovirus. 77 …”

Section: Discussionmentioning

confidence: 99%

Antigen-adjuvant interactions, stability, and immunogenicity profiles of a SARS-CoV-2 receptor-binding domain (RBD) antigen formulated with aluminum salt and CpG adjuvants

Bajoria

Kaur

Kumru

et al. 2022

Human Vaccines & Immunotherapeutics

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Low-cost, refrigerator-stable COVID-19 vaccines will facilitate global access and improve vaccine coverage in low- and middle-income countries. To this end, subunit-based approaches targeting the receptor-binding domain (RBD) of SARS-CoV-2 Spike protein remain attractive. Antibodies against RBD neutralize SARS-CoV-2 by blocking viral attachment to the host cell receptor, ACE2. Here, a yeast-produced recombinant RBD antigen (RBD-L452K-F490W or RBD-J) was formulated with various combinations of aluminum-salt (Alhydrogel®, AH; AdjuPhos®, AP) and CpG 1018 adjuvants. We assessed the effect of antigen-adjuvant interactions on the stability and mouse immunogenicity of various RBD-J preparations. While RBD-J was 50% adsorbed to AH and <15% to AP, addition of CpG resulted in complete AH binding, yet no improvement in AP adsorption. ACE2 competition ELISA analyses of formulated RBD-J stored at varying temperatures (4, 25, 37°C) revealed that RBD-J was destabilized by AH, an effect exacerbated by CpG. DSC studies demonstrated that aluminum-salt and CpG adjuvants decrease the conformational stability of RBD-J and suggest a direct CpG-RBD-J interaction. Although AH+CpG-adjuvanted RBD-J was the least stable in vitro , the formulation was most potent at eliciting SARS-CoV-2 pseudovirus neutralizing antibodies in mice. In contrast, RBD-J formulated with AP+CpG showed minimal antigen-adjuvant interactions, a better stability profile, but suboptimal immune responses. Interestingly, the loss of in vivo potency associated with heat-stressed RBD-J formulated with AH+CpG after one dose was abrogated by a booster. Our findings highlight the importance of elucidating the key interrelationships between antigen-adjuvant interactions, storage stability, and in vivo performance to enable successful formulation development of stable and efficacious subunit vaccines.

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Section: Discussionmentioning

confidence: 99%

Antigen-adjuvant interactions, stability, and immunogenicity profiles of a SARS-CoV-2 receptor-binding domain (RBD) antigen formulated with aluminum salt and CpG adjuvants

Bajoria

Kaur

Kumru

et al. 2022

Human Vaccines & Immunotherapeutics

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“…The double-antigen sandwich method has been reported to have better sensitivity and specificity for hepatitis B virus core antibodies than the chemiluminescent microparticle immunoassay [28] . Another possible explanation is that the repertoire and avidity of the antibodies affects the titers and changes over time [29] . In general, the avidity (affinity for the antigen) of IgG remains low after vaccine administration.…”

Section: Discussionmentioning

confidence: 99%

Kinetics of anti-SARS-CoV-2 antibody titer in healthy adults up to 6 months after BNT162b2 vaccination measured by two immunoassays: A prospective cohort study in Japan

Matsuura

Fukushima

Nakagama

et al. 2022

Vaccine

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“…15 The avidity was determined by the colorimetric comparison of optical density values obtained using enzyme-linked immunosorbent assay with and without the addition of a 5.5 M urea treatment step. 38 Third, the difference in epitope 39 targeted by the two assays might also have affected the measured titers. A recent study demonstrated the different kinetics of the two immunoassays in healthy adults.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and safety of COVID-19 vaccine in lung cancer patients receiving anticancer treatment: A prospective multicenter cohort study

Nakashima

Ishida

Matsui

et al. 2022

Human Vaccines & Immunotherapeutics

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This study assessed the immunogenicity and safety of the BNT162b2 mRNA vaccine in lung cancer patients receiving anticancer treatment. We enrolled lung cancer patients receiving anticancer treatment and non-cancer patients; all participants were fully vaccinated with the BNT162b2 vaccine. Blood samples were collected before the first and second vaccinations and 4 ± 1 weeks after the second vaccination. Anti-severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein S1 subunit receptor-binding domain antibody titers were measured using the Architect SARS-CoV-2 IgG II Quant and Elecsys Anti-SARS-CoV-2 S assays. Fifty-five lung cancer patients and 38 non-cancer patients were included in the immunogenicity analysis. Lung cancer patients showed significant increase in the geometric mean antibody concentration, which was significantly lower than that in the non-cancer patients after the first (30 vs. 121 AU/mL, p < .001 on Architect; 4.0 vs 1.2 U/mL, p < .001 on Elecsys) and second vaccinations (1632 vs. 3472 AU/mL, p = .005 on Architect; 213 vs 573 A/mL, p = .002 on Elecsys). The adjusted odds ratio (aOR) for seroprotection was significantly lower ( p < .05) in lung cancer patients than that in non-cancer patients. Analysis of the anticancer treatment types showed that the aOR for seroprotection was significantly lower ( p < .05) in lung cancer patients receiving cytotoxic agents. They showed no increase in adverse reactions. BNT162b2 vaccination in lung cancer patients undergoing anticancer treatment significantly increased ( p < .05) antibody titers and showed acceptable safety. Immunogenicity in these patients could be inadequate compared with that in non-cancer patients.

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High-Resolution Linear Epitope Mapping of the Receptor Binding Domain of SARS-CoV-2 Spike Protein in COVID-19 mRNA Vaccine Recipients

Abstract: Establishing vaccine-based population immunity has been the key factor in attaining herd protection. Thanks to expedited worldwide research efforts, the potency of mRNA vaccines against the coronavirus disease 2019 (COVID-19) is now incontestable.

Cited by 18 publications

References 41 publications

Antigen-adjuvant interactions, stability, and immunogenicity profiles of a SARS-CoV-2 receptor-binding domain (RBD) antigen formulated with aluminum salt and CpG adjuvants

Antigen-adjuvant interactions, stability, and immunogenicity profiles of a SARS-CoV-2 receptor-binding domain (RBD) antigen formulated with aluminum salt and CpG adjuvants

Kinetics of anti-SARS-CoV-2 antibody titer in healthy adults up to 6 months after BNT162b2 vaccination measured by two immunoassays: A prospective cohort study in Japan

Immunogenicity and safety of COVID-19 vaccine in lung cancer patients receiving anticancer treatment: A prospective multicenter cohort study

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