scholarly journals Searching for an ideal vaccine candidate among different MERS coronavirus receptor-binding fragments—The importance of immunofocusing in subunit vaccine design

Vaccine ◽  
2014 ◽  
Vol 32 (46) ◽  
pp. 6170-6176 ◽  
Author(s):  
Cuiqing Ma ◽  
Lili Wang ◽  
Xinrong Tao ◽  
Naru Zhang ◽  
Yang Yang ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Vaccine Design ◽  
Ideal Vaccine

scholarly journals Cryo-EM structure of S-Trimer, a subunit vaccine candidate for COVID-19

2021 ◽  
Author(s):  
Jiahao Ma ◽  
Danmei Su ◽  
Yinyan Sun ◽  
Xueqin Huang ◽  
Ying Liang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Receptor Binding ◽  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Phase 1 ◽  
Full Length ◽  
Effective Vaccine ◽  
S Protein ◽  
Closed Conformation ◽  
A Subunit

Within a year after its emergence, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 100 million people worldwide with a death toll over 2 million. Vaccination remains the best hope to ultimately put this pandemic to an end. Here, using Trimer-Tag technology, we produced both wild-type (WT) and furin site mutant (MT) S-Trimers for COVID-19 vaccine studies. Cryo-EM structures of the WT and MT S-Trimers, determined at 3.2 Å and 2.6 Å respectively, revealed that both antigens adopt a tightly closed conformation and their structures are essentially identical to that of the previously solved full-length WT S protein in detergent. The tightly closed conformation is stabilized by fatty acid and polysorbate 80 binding at the receptor binding domains (RBDs) and the N terminal domains (NTDs) respectively. Additionally, we identified an important pH switch in the WT S-Trimer that shows dramatic conformational change and accounts for its increased stability at lower pH. These results validate Trimer-Tag as a platform technology in production of metastable WT S-Trimer as a candidate for COVID-19 subunit vaccine. IMPORTANCE Effective vaccine against SARS-CoV-2 is critical to end the COVID-19 pandemic. Here, using Trimer-Tag technology, we are able to produce stable and large quantities of WT S-Trimer, a subunit vaccine candidate for COVID-19 with high safety and efficacy from animal and Phase 1 clinical trial studies. Cryo-EM structures of the S-Trimer subunit vaccine candidate show that it predominately adopts tightly closed pre-fusion state, and resembles that of the native and full-length spike in detergent, confirming its structural integrity. WT S-Trimer is currently being evaluated in global Phase 2/3 clinical trial. Combining with published structures of the S protein, we also propose a model to dissect the conformation change of the spike protein before receptor binding.

A proof of concept for structure-based vaccine design targeting RSV in humans

Science ◽  
2019 ◽  
Vol 365 (6452) ◽  
pp. 505-509 ◽  
Author(s):  
Michelle C. Crank ◽  
Tracy J. Ruckwardt ◽  
Man Chen ◽  
Kaitlyn M. Morabito ◽  
Emily Phung ◽  
...  
Keyword(s):  
Subunit Vaccine ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Level Structure ◽  
Vaccine Design ◽  
Atomic Level ◽  
Surface Proteins ◽  
Proof Of Concept ◽  
Syncytial Virus ◽  
Viral Surface

Technologies that define the atomic-level structure of neutralization-sensitive epitopes on viral surface proteins are transforming vaccinology and guiding new vaccine development approaches. Previously, iterative rounds of protein engineering were performed to preserve the prefusion conformation of the respiratory syncytial virus (RSV) fusion (F) glycoprotein, resulting in a stabilized subunit vaccine candidate (DS-Cav1), which showed promising results in mice and macaques. Here, phase I human immunogenicity data reveal a more than 10-fold boost in neutralizing activity in serum from antibodies targeting prefusion-specific surfaces of RSV F. These findings represent a clinical proof of concept for structure-based vaccine design, suggest that development of a successful RSV vaccine will be feasible, and portend an era of precision vaccinology.

scholarly journals Design of a companion bioinformatic tool to detect the emergence and geographical distribution of SARS-CoV-2 Spike protein genetic variants

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Alice Massacci ◽  
Eleonora Sperandio ◽  
Lorenzo D’Ambrosio ◽  
Mariano Maffei ◽  
Fabio Palombo ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Consensus Sequence ◽  
Cell Epitope ◽  
Vaccine Design ◽  
Binding Domain ◽  
Spike Protein ◽  
Antibody Activity ◽  
Binding Motif ◽  
Receptor Binding Domain ◽  
The Impact

Abstract Background Tracking the genetic variability of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) is a crucial challenge. Mainly to identify target sequences in order to generate robust vaccines and neutralizing monoclonal antibodies, but also to track viral genetic temporal and geographic evolution and to mine for variants associated with reduced or increased disease severity. Several online tools and bioinformatic phylogenetic analyses have been released, but the main interest lies in the Spike protein, which is the pivotal element of current vaccine design, and in the Receptor Binding Domain, that accounts for most of the neutralizing the antibody activity. Methods Here, we present an open-source bioinformatic protocol, and a web portal focused on SARS-CoV-2 single mutations and minimal consensus sequence building as a companion vaccine design tool. Furthermore, we provide immunogenomic analyses to understand the impact of the most frequent RBD variations. Results Results on the whole GISAID sequence dataset at the time of the writing (October 2020) reveals an emerging mutation, S477N, located on the central part of the Spike protein Receptor Binding Domain, the Receptor Binding Motif. Immunogenomic analyses revealed some variation in mutated epitope MHC compatibility, T-cell recognition, and B-cell epitope probability for most frequent human HLAs. Conclusions This work provides a framework able to track down SARS-CoV-2 genomic variability.

scholarly journals Evaluation of a subunit vaccine candidate (Biotech Vac Cox) against Eimeria spp. in broiler chickens

2021 ◽  
pp. 101329
Author(s):  
Emanuel Gumina ◽  
Jeffrey W. Hall ◽  
Bruno Vecchi ◽  
Xochitl Hernandez-Velasco ◽  
Brett Lumpkins ◽  
...  
Keyword(s):  
Broiler Chickens ◽  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Eimeria Spp ◽  
A Subunit

scholarly journals A Phase 1/2 Clinical Trial Evaluating Safety and Immunogenicity of a Varicella Zoster Glycoprotein E Subunit Vaccine Candidate in Young and Older Adults

2012 ◽  
Vol 206 (8) ◽  
pp. 1280-1290 ◽  
Author(s):  
Isabel Leroux-Roels ◽  
Geert Leroux-Roels ◽  
Frédéric Clement ◽  
Pierre Vandepapelière ◽  
Ventzislav Vassilev ◽  
...  
Keyword(s):  
Older Adults ◽  
Clinical Trial ◽  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Phase 1 ◽  
Glycoprotein E ◽  
Varicella Zoster

Penton base induces better protective immune responses than fiber and hexon as a subunit vaccine candidate against adenoviruses

Vaccine ◽  
2018 ◽  
Vol 36 (29) ◽  
pp. 4287-4297 ◽  
Author(s):  
Kai Hu ◽  
Ming Fu ◽  
Xinmeng Guan ◽  
Di Zhang ◽  
Xu Deng ◽  
...  
Keyword(s):  
Immune Responses ◽  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Penton Base ◽  
A Subunit

Immunological and physical evaluation of the multistage tuberculosis subunit vaccine candidate H56/CAF01 formulated as a spray-dried powder

Vaccine ◽  
2018 ◽  
Vol 36 (23) ◽  
pp. 3331-3339 ◽  
Author(s):  
Aneesh Thakur ◽  
Pall Thor Ingvarsson ◽  
Signe Tandrup Schmidt ◽  
Fabrice Rose ◽  
Peter Andersen ◽  
...  
Keyword(s):  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Physical Evaluation ◽  
Spray Dried

scholarly journals A novel Schmallenberg virus subunit vaccine candidate protects IFNAR-/- mice against virulent SBV challenge

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hani Boshra ◽  
Gema Lorenzo ◽  
Diego Charro ◽  
Sandra Moreno ◽  
Gabriel Soares Guerra ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Clinical Signs ◽  
Interferon Γ ◽  
Schmallenberg Virus ◽  
Immune Protection ◽  
Large Ruminant ◽  
Economical Alternative

AbstractSchmallenberg virus (SBV), an arthropod-transmitted pathogenic bunyavirus, continues to be a threat to the European livestock industry, causing morbidity and mortality among young ruminant livestock. Here, we describe a novel SBV subunit vaccine, based on bacterially expressed SBV nucleoprotein (SBV-N) administered with a veterinary-grade Saponin adjuvant. When assayed in an IFNAR-/- mouse model, SBV-N with Saponin induced strong non-neutralizing broadly virus-reactive antibodies, decreased clinical signs, as well as significantly reduced viremia. Vaccination assays also suggest that this level of immune protection is cell mediated, as evidenced by the lack of neutralizing antibodies, as well as interferon-γ secretion observed in vitro. Therefore, based on these results, bacterially expressed SBV-N, co-administered with veterinary-grade Saponin adjuvant may serve as a promising economical alternative to current SBV vaccines, and warrant further evaluation in large ruminant animal models. Moreover, we propose that this strategy may be applicable to other bunyaviruses.

Construction and immunogenic studies of a mFc fusion receptor binding domain (RBD) of spike protein as a subunit vaccine against SARS-CoV-2 infection

2020 ◽  
Vol 56 (61) ◽  
pp. 8683-8686 ◽  
Author(s):  
Xiaoxiao Qi ◽  
Bixia Ke ◽  
Qian Feng ◽  
Deying Yang ◽  
Qinghai Lian ◽  
...  
Keyword(s):  
Amino Acid ◽  
Fusion Protein ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Humoral And Cellular Immunity ◽  
A Subunit

Herein, we report that a recombinant fusion protein, containing a 457 amino acid SARS-CoV-2 receptor binding domain and a mouse IgG1 Fc domain, could induce highly potent neutralizing antibodies and stimulate humoral and cellular immunity in mice.

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