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Rapid Development of SARS-CoV-2 Spike Protein Receptor-Binding Domain Self-Assembled Nanoparticle Vaccine Candidates.

ABSTRACT: The coronavirus disease pandemic of 2019 (COVID-19) caused by the novel SARS-CoV-2 coronavirus resulted in economic losses and threatened human health worldwide. The pandemic highlights an urgent need for a stable, easily produced, and effective vaccine. SARS-CoV-2 uses the spike protein receptor-binding domain (RBD) to bind its cognate receptor, angiotensin-converting enzyme 2 (ACE2), and initiate membrane fusion. Thus, the RBD is an ideal target for vaccine development. In this study, we designed three different RBD-conjugated nanoparticle vaccine candidates, namely, RBD-Ferritin (24-mer), RBD-mi3 (60-mer), and RBD-I53-50 (120-mer), via covalent conjugation using the SpyTag-SpyCatcher system. When mice were immunized with the RBD-conjugated nanoparticles (NPs) in conjunction with the AddaVax or Sigma Adjuvant System, the resulting antisera exhibited 8- to 120-fold greater neutralizing activity against both a pseudovirus and the authentic virus than those of mice immunized with monomeric RBD. Most importantly, sera from mice immunized with RBD-conjugated NPs more efficiently blocked the binding of RBD to ACE2 in vitro, further corroborating the promising immunization effect. Additionally, the vaccine has distinct advantages in terms of a relatively simple scale-up and flexible assembly. These results illustrate that the SARS-CoV-2 RBD-conjugated nanoparticles developed in this study are a competitive vaccine candidate and that the carrier nanoparticles could be adopted as a universal platform for a future vaccine development.

SUBMITTER: Kang YF

PROVIDER: S-EPMC7839421 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Rapid Development of SARS-CoV-2 Spike Protein Receptor-Binding Domain Self-Assembled Nanoparticle Vaccine Candidates.

Kang Yin-Feng YF Sun Cong C Zhuang Zhen Z Yuan Run-Yu RY Zheng Qingbing Q Li Jiang-Ping JP Zhou Ping-Ping PP Chen Xin-Chun XC Liu Zhe Z Zhang Xiao X Yu Xiao-Hui XH Kong Xiang-Wei XW Zhu Qian-Ying QY Zhong Qian Q Xu Miao M Zhong Nan-Shan NS Zeng Yi-Xin YX Feng Guo-Kai GK Ke Changwen C Zhao Jin-Cun JC Zeng Mu-Sheng MS

ACS nano 20210119 2

The coronavirus disease pandemic of 2019 (COVID-19) caused by the novel SARS-CoV-2 coronavirus resulted in economic losses and threatened human health worldwide. The pandemic highlights an urgent need for a stable, easily produced, and effective vaccine. SARS-CoV-2 uses the spike protein receptor-binding domain (RBD) to bind its cognate receptor, angiotensin-converting enzyme 2 (ACE2), and initiate membrane fusion. Thus, the RBD is an ideal target for vaccine development. In this study, we desig ...[more]

PMID: 33464829

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Project description:BACKGROUND:NVX-CoV2373 is a recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant. METHODS:We initiated a randomized, placebo-controlled, phase 1-2 trial to evaluate the safety and immunogenicity of the rSARS-CoV-2 vaccine (in 5-?g and 25-?g doses, with or without Matrix-M1 adjuvant, and with observers unaware of trial-group assignments) in 131 healthy adults. In phase 1, vaccination comprised two intramuscular injections, 21 days apart. The primary outcomes were reactogenicity; laboratory values (serum chemistry and hematology), according to Food and Drug Administration toxicity scoring, to assess safety; and IgG anti-spike protein response (in enzyme-linked immunosorbent assay [ELISA] units). Secondary outcomes included unsolicited adverse events, wild-type virus neutralization (microneutralization assay), and T-cell responses (cytokine staining). IgG and microneutralization assay results were compared with 32 (IgG) and 29 (neutralization) convalescent serum samples from patients with Covid-19, most of whom were symptomatic. We performed a primary analysis at day 35. RESULTS:After randomization, 83 participants were assigned to receive the vaccine with adjuvant and 25 without adjuvant, and 23 participants were assigned to receive placebo. No serious adverse events were noted. Reactogenicity was absent or mild in the majority of participants, more common with adjuvant, and of short duration (mean, ?2 days). One participant had mild fever that lasted 1 day. Unsolicited adverse events were mild in most participants; there were no severe adverse events. The addition of adjuvant resulted in enhanced immune responses, was antigen dose-sparing, and induced a T helper 1 (Th1) response. The two-dose 5-?g adjuvanted regimen induced geometric mean anti-spike IgG (63,160 ELISA units) and neutralization (3906) responses that exceeded geometric mean responses in convalescent serum from mostly symptomatic Covid-19 patients (8344 and 983, respectively). CONCLUSIONS:At 35 days, NVX-CoV2373 appeared to be safe, and it elicited immune responses that exceeded levels in Covid-19 convalescent serum. The Matrix-M1 adjuvant induced CD4+ T-cell responses that were biased toward a Th1 phenotype. (Funded by the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number, NCT04368988).

Project description:BackgroundThe pandemic situation of SARS-CoV-2 infection has sparked global concern due to the disease COVID-19 caused by it. Since the first cluster of confirmed cases in China in December 2019, the infection has been reported across the continents and inflicted upon a substantial number of populations.MethodThis study is focused on immunoinformatics analyses of the SARS-CoV-2 spike glycoprotein (S protein) which is key for the viral attachment to human host cells. Computational analyses were carried out for the prediction of B-cell and T-cell (MHC class I and II) epitopes of S protein and the analyses were extended further for the prediction of their immunogenic properties. The interaction and binding affinity of T-cell epitopes with HLA-B7 were also investigated by molecular docking.ResultThree distinct epitopes for vaccine design were predicted from the sequence of S protein. The potential B-cell epitope was KNHTSPDVDLG possessing the highest antigenicity score of 1.4039 among other B-cell epitopes. T-cell epitope for human MHC class I was VVVLSFELL with an antigenicity score of 1.0909 and binding ability to 29 MHC-I alleles. The predicted T-cell epitope for human MHC class II molecule was VVIGIVNNT with a corresponding 1.3063 antigenicity score, less digesting enzymes, and 7 MHC-II alleles binding ability. All these three peptides were predicted to be highly antigenic, non-allergenic, and non-toxic. Analyses of the physiochemical properties of these predicted epitopes indicate their stable nature for plausible vaccine design. Furthermore, molecular docking investigation between the MHC class-I epitopes and human HLA-B7 reflects the stable interaction with high affinity among them.ConclusionThe present study posits three potential epitopes of S protein of SARS-CoV-2 predicted by immunoinformatic methods based on their immunogenic properties and interactions with the host counterpart that can facilitate the development of vaccine against SARS-CoV-2. This study can act as the springboard for the future development of the COVID-19 vaccine.

Dataset Information

Rapid Development of SARS-CoV-2 Spike Protein Receptor-Binding Domain Self-Assembled Nanoparticle Vaccine Candidates.

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Rapid Development of SARS-CoV-2 Spike Protein Receptor-Binding Domain Self-Assembled Nanoparticle Vaccine Candidates.

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