Preclinical study of formulated recombinant nucleocapsid protein, the receptor binding domain of the spike protein, and truncated spike (S1) protein as vaccine candidates against COVID-19 in animal models

Nazarian, Shahram; Olad, Gholamreza; Abdolhamidi, Raziyeh; Motamedi, Mohammad Javad; Kazemi, Rouhollah; Kordbacheh, Emad; Felagari, Alireza; Olad, Hanieh; Ahmadi, Ali; Bahiraee, Alireza; Farahani, Parisa; Haghighi, Ladan; Hassani, Faezeh Arab; Hajhassan, Vahideh; Nadi, Mona; Sheikhi, Abdolkarim; Salimian, Jafar; Amani, Jafar

doi:10.1016/j.molimm.2022.06.007

Cited by 4 publications

(4 citation statements)

References 59 publications

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“…The RBD has dominant epitopes in the S protein that effectively induces neutralizing antibodies 16,17 . During a previous preclinical study, an RBD‐based protein recombinant vaccine candidate was developed which showed promising results regarding immunogenicity and safety in mice, rabbits, and primates 18 . This phase 1 trial aimed to evaluate the safety and immunogenicity of a recombinant RBD‐based protein subunit vaccine (Noora vaccine) against COVID‐19 in an Iranian adult population.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Safety and immunogenicity of a recombinant receptor‐binding domain‐based protein subunit vaccine (Noora vaccine™) against COVID‐19 in adults: A randomized, double‐blind, placebo‐controlled, Phase 1 trial

Salimian

Ahmadi

Amani

et al. 2022

Journal of Medical Virology

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The development of a safe and effective vaccine is essential to protect populations against coronavirus disease 2019 (COVID‐19). There are several vaccine candidates under investigation with different mechanisms of action. In the present study, we have evaluated the safety and immunogenicity of a recombinant receptor‐binding domain (RBD)‐based protein subunit vaccine (Noora vaccine) against COVID‐19 in adults. This Phase 1 trial is a randomized, double‐blind, placebo‐controlled study to evaluate the safety and immunogenicity of the recombinant RBD‐based protein subunit vaccine (Noora vaccine) against COVID‐19 in healthy adults volunteers. Eligible participants were included in this study after evaluating their health status and considering the exclusion criteria. They were then randomized into three groups and received three doses of vaccine (80 µg, 120 µg, and placebo) on Days 0, 21, and 35. Primary outcomes including solicited, unsolicited, and medically attended adverse events were recorded during this study. Secondary outcomes including the humoral and cellular immunity (including anti‐RBD IgG antibody and neutralizing antibody) were measured on Days 0, 21, 28, 35, 42, and 49 by using the ELISA kit and the Virus Neutralization Test (VNT) was performed on day 49. Totally 70 cases were included in this Phase 1 trial and 60 of them completed the study. Safety assessments showed no severe adverse events. Local pain at the vaccine injection site occurred in 80% of the vaccinated volunteers. Induration and redness at the injection site were the other adverse reactions of this vaccine. There was no significant difference between the studied groups regarding adverse reactions. Anti‐RBD IgG antibody and neutralizing antibody assessment showed significant seroconversion in comparison to the placebo group (80%, and 100% respectively, p < 0.001). The cellular immunity panel also showed mild to moderate induction of TH1 responses and the VNT showed 78% of seroprotection. The results of this Phase 1 trial showed acceptable safety without serious adverse events and significant seroconversions in the humoral and cellular immunity panel. The dose of 80 µg is an appropriate dose for injection in the next phases of the trial.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: Safety and immunogenicity of a recombinant receptor‐binding domain‐based protein subunit vaccine (Noora vaccine™) against COVID‐19 in adults: A randomized, double‐blind, placebo‐controlled, Phase 1 trial

Salimian

Ahmadi

Amani

et al. 2022

Journal of Medical Virology

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“…In all cases, the authors revealed the absence of toxicity and intensive production of specific IgG antibodies, as well as cellular responses, especially when the SARS-CoV-2 antigens were adjuvanted with AS03 and Montanide. Interestingly, neutralizing antibodies were produced only when animals were immunized with Alum adjuvant [ 53 ].…”

Section: Development Of N-based Broadly Protective Vaccine Prototypesmentioning

confidence: 99%

Overview of Nucleocapsid-Targeting Vaccines against COVID-19

Rak,

Isakova-Sivak,

Rudenko

2023

Vaccines

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The new SARS-CoV-2 coronavirus, which emerged in late 2019, is a highly variable causative agent of COVID-19, a contagious respiratory disease with potentially severe complications. Vaccination is considered the most effective measure to prevent the spread and complications of this infection. Spike (S) protein-based vaccines were very successful in preventing COVID-19 caused by the ancestral SARS-CoV-2 strain; however, their efficacy was significantly reduced when coronavirus variants antigenically different from the original strain emerged in circulation. This is due to the high variability of this major viral antigen caused by escape from the immunity caused by the infection or vaccination with spike-targeting vaccines. The nucleocapsid protein (N) is a much more conserved SARS-CoV-2 antigen than the spike protein and has therefore attracted the attention of scientists as a promising target for broad-spectrum vaccine development. Here, we summarized the current data on various N-based COVID-19 vaccines that have been tested in animal challenge models or clinical trials. Despite the high conservatism of the N protein, escape mutations gradually occurring in the N sequence can affect its protective properties. During the three years of the pandemic, at least 12 mutations have arisen in the N sequence, affecting more than 40 known immunogenic T-cell epitopes, so the antigenicity of the N protein of recent SARS-CoV-2 variants may be altered. This fact should be taken into account as a limitation in the development of cross-reactive vaccines based on N-protein.

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“…Moreover, sera from the immunized mice showed cross-reactivity with RBD from Alpha and Beta VOCs [ 84 ]. A combination of spike and nucleocapsid proteins using a conventional formulation with aluminum hydroxide, lipids, or other adjuvants has shown induction of humoral and cellular response [ 85 , 86 , 87 , 88 , 89 ]. Moreover, formulation of spike + nucleocapsid with cationic or anionic lipids showed that this combination of antigens induced IgG and IgA antibodies and production of IL-5 and IFN- γ [ 86 ].…”

Section: The Potential Use Of Nucleocapsid As Vaccine Antigenmentioning

confidence: 99%

The Key to Increase Immunogenicity of Next-Generation COVID-19 Vaccines Lies in the Inclusion of the SARS-CoV-2 Nucleocapsid Protein

Mendoza-Ramírez,

García-Cordero,

Shrivastava

et al. 2024

Journal of Immunology Research

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Vaccination is one of the most effective prophylactic public health interventions for the prevention of infectious diseases such as coronavirus disease (COVID-19). Considering the ongoing need for new COVID-19 vaccines, it is crucial to modify our approach and incorporate more conserved regions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to effectively address emerging viral variants. The nucleocapsid protein is a structural protein of SARS-CoV-2 that is involved in replication and immune responses. Furthermore, this protein offers significant advantages owing to the minimal accumulation of mutations over time and the inclusion of key T-cell epitopes critical for SARS-CoV-2 immunity. A novel strategy that may be suitable for the new generation of vaccines against COVID-19 is to use a combination of antigens, including the spike and nucleocapsid proteins, to elicit robust humoral and potent cellular immune responses, along with long-lasting immunity. The strategic use of multiple antigens aims to enhance vaccine efficacy and broaden protection against viruses, including their variants. The immune response against the nucleocapsid protein from other coronavirus is long-lasting, and it can persist up to 11 years post-infection. Thus, the incorporation of nucleocapsids (N) into vaccine design adds an important dimension to vaccination efforts and holds promise for bolstering the ability to combat COVID-19 effectively. In this review, we summarize the preclinical studies that evaluated the use of the nucleocapsid protein as antigen. This study discusses the use of nucleocapsid alone and its combination with spike protein or other proteins of SARS-CoV-2.

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Preclinical study of formulated recombinant nucleocapsid protein, the receptor binding domain of the spike protein, and truncated spike (S1) protein as vaccine candidates against COVID-19 in animal models

Cited by 4 publications

References 59 publications

RETRACTED: Safety and immunogenicity of a recombinant receptor‐binding domain‐based protein subunit vaccine (Noora vaccine™) against COVID‐19 in adults: A randomized, double‐blind, placebo‐controlled, Phase 1 trial

RETRACTED: Safety and immunogenicity of a recombinant receptor‐binding domain‐based protein subunit vaccine (Noora vaccine™) against COVID‐19 in adults: A randomized, double‐blind, placebo‐controlled, Phase 1 trial

Overview of Nucleocapsid-Targeting Vaccines against COVID-19

The Key to Increase Immunogenicity of Next-Generation COVID-19 Vaccines Lies in the Inclusion of the SARS-CoV-2 Nucleocapsid Protein

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