Antibody-Based Immunotherapeutic Strategies for COVID-19

Hussen, Jamal; Kandeel, Mahmoud; Hemida, Maged Gomaa; Al-Mubarak, Abdullah I. A.

doi:10.3390/pathogens9110917

Cited by 16 publications

(15 citation statements)

References 105 publications

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“…Targets considered in these domains and potential treatments include: interferons β1a and β1b; IL-6 receptor (tocilizumab, sarilumab, situximab); IL-1 receptor/IL-1β (anakinra, canakinumab); less specific immunosuppressive therapies (dexamethasone); and ongoing clinical trials of immunomodulatory antibodies. 193 …”

Section: Translating To Therapies For Sars-cov-2mentioning

confidence: 99%

COVID-19 and Cardiovascular Disease

Chung

Zidar

Bristow

et al. 2021

Circulation Research

293

266

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A pandemic of historic impact, coronavirus disease 2019 (COVID-19) has potential consequences on the cardiovascular health of millions of people who survive infection worldwide. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, can infect the heart, vascular tissues, and circulating cells through ACE2 (angiotensin-converting enzyme 2), the host cell receptor for the viral spike protein. Acute cardiac injury is a common extrapulmonary manifestation of COVID-19 with potential chronic consequences. This update provides a review of the clinical manifestations of cardiovascular involvement, potential direct SARS-CoV-2 and indirect immune response mechanisms impacting the cardiovascular system, and implications for the management of patients after recovery from acute COVID-19 infection.

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Section: Translating To Therapies For Sars-cov-2mentioning

confidence: 99%

COVID-19 and Cardiovascular Disease

Chung

Zidar

Bristow

et al. 2021

Circulation Research

293

266

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“…The receptor-binding domain (RBD) of S engages the primary host cell receptor, Angiotensin-converting enzyme 2 (ACE2), for both SARS-CoV-2 and SARS-CoV-1, making RBD a promising domain for vaccine elicited immune focus (10)(11)(12). Moreover, many of the potently neutralizing monoclonal antibodies isolated against SARS-CoV-2 target the RBD (13,14). Vaccination of nonhuman primates with RBDencoding RNA or DNA protects against respiratory tract challenge, indicating that immune responses to the RBD can prevent viral replication (15,16).…”

Section: Introductionmentioning

confidence: 99%

Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques

King

Joyce²,

Naouar³

et al. 2021

Preprint

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Emergence of novel variants of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean neutralizing antibody titers of 14,000-21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within four days in 7 of 8 animals receiving 50 μg RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only ~2-fold relative to USA-WA1. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-like betacoronavirus vaccine development.

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“…Such work as well as other studies on the Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV suggest that viral S protein could represent the main target for the development of vaccines against SARS-CoV-2 ( Fukushi et al, 2006 , 2018 ; Prompetchara et al, 2020 ). This is further supported by the isolation and development of several therapeutic human nAbs against the SARS-CoV-2 S protein and their ability to neutralize and block viral entry and/or cell-cell spread at very low concentrations and sometimes to confer prophylactic and therapeutic protection in animals and humans ( Hussen et al, 2020 ; Papageorgiou and Mohsin, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Synthetic SARS-CoV-2 Spike-Based DNA Vaccine Elicits Robust and Long-Lasting Th1 Humoral and Cellular Immunity in Mice

et al. 2021

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The ongoing global pandemic of coronavirus disease 2019 (COVID-19) calls for an urgent development of effective and safe prophylactic and therapeutic measures. The spike (S) glycoprotein of severe acute respiratory syndrome-coronavirus (SARS-CoV-2) is a major immunogenic and protective protein and plays a crucial role in viral pathogenesis. In this study, we successfully constructed a synthetic codon-optimized DNA-based vaccine as a countermeasure against SARS-CoV-2, denoted VIU-1005. The design was based on a codon-optimized coding sequence of a consensus full-length S glycoprotein. The immunogenicity of the vaccine was tested in two mouse models (BALB/c and C57BL/6J). Th1-skewed systemic S-specific IgG antibodies and neutralizing antibodies (nAbs) were significantly induced in both models 4 weeks after three injections with 100 μg of the VIU-1005 vaccine via intramuscular needle injection but not intradermal or subcutaneous routes. Such immunization induced long-lasting IgG and memory T cell responses in mice that lasted for at least 6 months. Interestingly, using a needle-free system, we showed an enhanced immunogenicity of VIU-1005 in which lower or fewer doses were able to elicit significantly high levels of Th1-biased systemic S-specific immune responses, as demonstrated by the significant levels of binding IgG antibodies, nAbs and IFN-γ, TNF and IL-2 cytokine production from memory CD8+ and CD4+ T cells in BALB/c mice. Furthermore, compared to intradermal needle injection, which failed to induce any significant immune response, intradermal needle-free immunization elicited a robust Th1-biased humoral response similar to that observed with intramuscular immunization. Together, our results demonstrate that the synthetic VIU-1005 candidate DNA vaccine is highly immunogenic and capable of inducing long-lasting Th1-skewed humoral and cellular immunity in mice. Furthermore, we show that the use of a needle-free system could enhance the immunogenicity and minimize doses needed to induce protective immunity in mice, supporting further preclinical and clinical testing of this candidate vaccine.

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Antibody-Based Immunotherapeutic Strategies for COVID-19

Cited by 16 publications

References 105 publications

COVID-19 and Cardiovascular Disease

COVID-19 and Cardiovascular Disease

Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques

Synthetic SARS-CoV-2 Spike-Based DNA Vaccine Elicits Robust and Long-Lasting Th1 Humoral and Cellular Immunity in Mice

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