A novel receptor-binding domain (RBD)-based mRNA vaccine against SARS-CoV-2

Tai, Wanbo; Zhang, Xiujuan; Drelich, Aleksandra; Shi, Juan; Hsu, Jason C.; Luchsinger, Larry L.; Hillyer, Christopher D.; Tseng, Chien Te K.; Jiang, Shibo; Du, Lanying

doi:10.1038/s41422-020-0387-5

Cited by 136 publications

(145 citation statements)

References 12 publications

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“…Mice immunized with the RBD exhibited no observable serum neutralizing activity after a single dose ( Figure 4C) despite having RBD-specific antibody titers that were similar to those in other groups ( Figure 4B). This discordance suggests that RBD binding titers may not be a strong correlate of neutralizing antibody responses in the context of vaccination, particularly for candidates based on the RBD alone (50,68,69). Notably, the full-length spike ELISA binding titers from animals immunized with the RBD were significantly lower than titers from the other groups ( Figure 4B), suggesting that immunization with monomeric RBD elicits antibodies to epitopes that are occluded in full-length spike, rendering them unable to neutralize virus.…”

Section: Discussionmentioning

confidence: 98%

A single immunization with spike-functionalized ferritin vaccines elicits neutralizing antibody responses against SARS-CoV-2 in mice

Chen

Zhang

Sanyal

et al. 2020

Preprint

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Development of a safe and effective SARS-CoV-2 vaccine is a public health priority. We designed subunit vaccine candidates using self-assembling ferritin nanoparticles displaying one of two multimerized SARS-CoV-2 spikes: full-length ectodomain (S-Fer) or a C-terminal 70 amino-acid deletion (SΔC-Fer). Ferritin is an attractive nanoparticle platform for production of vaccines and ferritin-based vaccines have been investigated in humans in two separate clinical trials. We confirmed proper folding and antigenicity of spike on the surface of ferritin by cryo-EM and binding to conformation-specific monoclonal antibodies. After a single immunization of mice with either of the two spike ferritin particles, a lentiviral SARS-CoV-2 pseudovirus assay revealed mean neutralizing antibody titers at least 2-fold greater than those in convalescent plasma from COVID-19 patients. Additionally, a single dose of SΔC-Fer elicited significantly higher neutralizing responses as compared to immunization with the spike receptor binding domain (RBD) monomer or spike ectodomain trimer alone. After a second dose, mice immunized with SΔC-Fer exhibited higher neutralizing titers than all other groups. Taken together, these results demonstrate that multivalent presentation of SARS-CoV-2 spike on ferritin can notably enhance elicitation of neutralizing antibodies, thus constituting a viable strategy for single-dose vaccination against COVID-19.

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Section: Discussionmentioning

confidence: 98%

A single immunization with spike-functionalized ferritin vaccines elicits neutralizing antibody responses against SARS-CoV-2 in mice

Chen

Zhang

Sanyal

et al. 2020

Preprint

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“…ARCoV is currently being evaluated in phase 1 clinical trials. Other mRNA vaccine candidates showed immunogenicity by eliciting potent neutralizing antibodies in mice and/or NHPs ( 121 , 122 ).…”

Section: Nucleic Acid Vaccinesmentioning

confidence: 99%

COVID-19: Coronavirus Vaccine Development Updates

et al. 2020

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Coronavirus Disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a newly emerged coronavirus, and has been pandemic since March 2020 and led to many fatalities. Vaccines represent the most efficient means to control and stop the pandemic of COVID-19. However, currently there is no effective COVID-19 vaccine approved to use worldwide except for two human adenovirus vector vaccines, three inactivated vaccines, and one peptide vaccine for early or limited use in China and Russia. Safe and effective vaccines against COVID-19 are in urgent need. Researchers around the world are developing 213 COVID-19 candidate vaccines, among which 44 are in human trials. In this review, we summarize and analyze vaccine progress against SARS-CoV, Middle-East respiratory syndrome Coronavirus (MERS-CoV), and SARS-CoV-2, including inactivated vaccines, live attenuated vaccines, subunit vaccines, virus like particles, nucleic acid vaccines, and viral vector vaccines. As SARS-CoV-2, SARS-CoV, and MERS-CoV share the common genus, Betacoronavirus, this review of the major research progress will provide a reference and new insights into the COVID-19 vaccine design and development.

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“…It was subsequently revealed that spike glycoprotein (S protein) of SARS-CoV-2 was responsible for viral infection via interaction with angiotensin-converting enzyme 2 (ACE2) receptors on human cell membranes and that the antibodies generated against the S protein effectively neutralize viral entry to human cells [ 26 , 27 ]. The receptor-binding domain (RBD) is the functional domain within the S protein that first engages with ACE2, is considered a prime target for COVID-19 vaccine development, and can be produced as a recombinant antigen to generate directed antibody responses [ 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Lipid-based vaccine nanoparticles for induction of humoral immune responses against HIV-1 and SARS-CoV-2

Park

Bazzill

Son

et al. 2021

Journal of Controlled Release

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The current health crisis of corona virus disease 2019 (COVID-19) highlights the urgent need for vaccine systems that can generate potent and protective immune responses. Protein vaccines are safe, but conventional approaches for protein-based vaccines often fail to elicit potent and long-lasting immune responses. Nanoparticle vaccines designed to co-deliver protein antigens and adjuvants can promote their delivery to antigen-presenting cells and improve immunogenicity. However, it remains challenging to develop vaccine nanoparticles that can preserve and present conformational epitopes of protein antigens for induction of neutralizing antibody responses. Here, we have designed a new lipid-based nanoparticle vaccine platform (NVP) that presents viral proteins (HIV-1 and SARS-CoV-2 antigens) in a conformational manner for induction of antigen-specific antibody responses. We show that NVP was readily taken up by dendritic cells (DCs) and promoted DC maturation and antigen presentation. NVP loaded with BG505.SOSIP.664 (SOSIP) or SARS-CoV-2 receptor-binding domain (RBD) was readily recognized by neutralizing antibodies, indicating the conformational display of antigens on the surfaces of NVP. Rabbits immunized with SOSIP-NVP elicited strong neutralizing antibody responses against HIV-1. Furthermore, mice immunized with RBD-NVP induced robust and long-lasting antibody responses against RBD from SARS-CoV-2. These results suggest that NVP is a promising platform technology for vaccination against infectious pathogens.

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A novel receptor-binding domain (RBD)-based mRNA vaccine against SARS-CoV-2

Cited by 136 publications

References 12 publications

A single immunization with spike-functionalized ferritin vaccines elicits neutralizing antibody responses against SARS-CoV-2 in mice

A single immunization with spike-functionalized ferritin vaccines elicits neutralizing antibody responses against SARS-CoV-2 in mice

COVID-19: Coronavirus Vaccine Development Updates

Lipid-based vaccine nanoparticles for induction of humoral immune responses against HIV-1 and SARS-CoV-2

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