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Vaccines
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Receptor-Binding Domain-Based Vaccines Against SARS-CoV-2
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Receptor-Binding Domain-Based Vaccines Against SARS-CoV-2

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "COVID-19 Vaccines and Vaccination".

Deadline for manuscript submissions: closed (28 February 2026) | Viewed by 3469

Special Issue Editor

Dr. Puthupparampil Scaria

E-Mail Website
Guest Editor
National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA
Interests: vaccine development; conjugate vaccines; nanotechnology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The emergence of the COVID-19 pandemic in 2019 led to unprecedented efforts in vaccine development. Effective vaccines using various platforms have played a vital role in controlling the pandemic. Initially, most subunit vaccines targeted the spike protein of SARS-CoV-2. However, vaccines based on the spike protein's receptor-binding domain (RBD) have also proven themselves to be effective. The neutralizing antibodies target the RBD, which is smaller than the whole spike protein. This focus can enhance manufacturing and help minimize non-neutralizing antibody production. This Special Issue invites submissions of original research, reviews, clinical trial results, and opinions related to RBD and other spike protein subdomains.

Dr. Puthupparampil Scaria
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • RBD vaccine
  • COVID-19
  • vaccine
  • SARS-CoV-2

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Published Papers (2 papers)

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Research

17 pages, 2000 KB  
Article
Omicron KP.3 RBD-Containing Spike mRNA Vaccine Induces Broadly Neutralizing Antibodies with Protection Against SARS-CoV-2 Omicron Infection in Mice
by Xiaoqing Guan, Hansam Cho, Shengnan Qian, Qian Liu and Lanying Du
Vaccines 2026, 14(1), 78; https://doi.org/10.3390/vaccines14010078 - 11 Jan 2026
Viewed by 911
Abstract
Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the global COVID-19 pandemic, which led to hundreds of millions of human infections and more than seven million deaths worldwide. Major variants of concern, particularly the Omicron variant and its associated subvariants, can [...] Read more.
Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the global COVID-19 pandemic, which led to hundreds of millions of human infections and more than seven million deaths worldwide. Major variants of concern, particularly the Omicron variant and its associated subvariants, can escape the vaccines developed so far to target previous strains/subvariants. Therefore, effective vaccines that broadly neutralize different Omicron subvariants and show good protective efficacy are needed to prevent further spread of Omicron. The spike (S) protein, including its receptor-binding domain (RBD), is a key vaccine target. Methods: Here, we designed a unique mRNA vaccine encoding Omicron-KP.3 RBD based on RBD-truncated S protein backbone of an earlier Omicron subvariant EG.5 (KP3 mRNA), and evaluated its stability, immunogenicity, neutralizing activity, and protective efficacy in a mouse model. Results: Our data showed that the nucleoside-modified, lipid nanoparticle-encapsulated mRNA vaccine was stable at various temperatures during the period of detection. In addition, the vaccine elicited potent antibody responses with broadly neutralizing activity against multiple Omicron subvariants, including KP.2, KP.3, XEC, and NB.1.8.1. This mRNA vaccine protected immunized transgenic mice from challenge with SARS-CoV-2 Omicron-KP.3. Immune serum also protected against subsequent virus challenge, with the level of protection associating positively with the serum neutralizing antibody titer. Conclusions: Taken together, the data presented herein suggest that this newly designed mRNA vaccine has potential against current and future Omicron subvariants. Full article
(This article belongs to the Special Issue Receptor-Binding Domain-Based Vaccines Against SARS-CoV-2)
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25 pages, 1908 KB  
Article
SARS-CoV-2 Receptor Binding Domain (RBD) Protein–Protein Conjugate Induces Similar or Better Antibody Responses as Spike mRNA in Rhesus Macaques
by Puthupparampil V. Scaria, Christopher G. Rowe, Ivan Kosik, Zhe Hu, Jonathan P. Renn, Nada Alani, Pinar Kemanli, Sachy Orr-Gonzalez, Lynn E. Lambert, Kayode Adeyemi, Justin Y. A. Doritchamou, Emma K. Barnafo, Kelly M. Rausch, Liya Muslinkina, Robert D. Morrison, John-Paul Todd, Dominic Esposito, Andrew Lees, Jonathan Yewdell and Patrick E. Duffy
Vaccines 2025, 13(6), 648; https://doi.org/10.3390/vaccines13060648 - 17 Jun 2025
Viewed by 2125
Abstract
Background/Objectives: Rapid development of vaccines against SARS-CoV-2 was pivotal to controlling the COVID-19 pandemic. The emergency also provided a rare opportunity to test novel vaccine platforms such as mRNA in large clinical trials. Most of the early vaccines used SARS-CoV-2 Spike protein [...] Read more.
Background/Objectives: Rapid development of vaccines against SARS-CoV-2 was pivotal to controlling the COVID-19 pandemic. The emergency also provided a rare opportunity to test novel vaccine platforms such as mRNA in large clinical trials. Most of the early vaccines used SARS-CoV-2 Spike protein as the target antigen. Nevertheless, subsequent studies have shown that Receptor Binding Domain (RBD) of Spike also can yield efficacious vaccines, and we previously demonstrated that chemical conjugation of RBD to a carrier protein, EcoCRM®, enhanced antibody responses and induced strong virus neutralization activity in mice. Methods: Here, we compared the immunogenicity of this conjugate to that of an approved mRNA vaccine from Pfizer/BioNTech in rhesus macaques over a period of nine months. Results: AS01-adjuvanted RBD conjugate induced a similar or better antibody response, receptor binding inhibition, and virus neutralization activity against different variants of SARS-CoV-2, compared to mRNA. IgG subclass profiles induced by conjugate and mRNA vaccines were initially dominated by IgG1 and IgG3 then switched to IgG2 and IgG4 dominant profiles during the subsequent six-month period. Polyclonal immune sera from the conjugate and mRNA had similar antibody avidity at multiple time points. Conclusions: In summary, antibody responses in rhesus macaques induced by the RBD-EcoCRM conjugate and the Spike mRNA vaccine are very similar. These results demonstrate the potential for the RBD-EcoCRM conjugate as a vaccine against SARS-CoV-2. Full article
(This article belongs to the Special Issue Receptor-Binding Domain-Based Vaccines Against SARS-CoV-2)
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