Immunogenicity and protective efficacy of rotavirus VP8<b>*</b>fused to cholera toxin B subunit in a mouse model

Xue, Miaoge; Yu, Linqi; Jia, Lianzhi; Li, Yijian; Zeng, Yuanjun; Li, Tingdong; Ge, Shuping; Xia, Ningshao

doi:10.1080/21645515.2016.1204501

Cited by 19 publications

(9 citation statements)

References 45 publications

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“…VP8* is the glycan-binding domain of rotavirus spike protein VP[4] that interacts with host glycan receptors as the first step of a rotavirus infection. Thus, VP8* serves as a key target for rotavirus vaccine development [ 15 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. When the P-VP8* proteins are expressed using the bacterial ( Escherichia coli, BL21 strain) system, the P 24 -VP8* nanoparticles assemble spontaneously [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

A Nanoparticle-Based Trivalent Vaccine Targeting the Glycan Binding VP8* Domains of Rotaviruses

Xia

Huang

Jiang

et al. 2021

Viruses

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Rotavirus causes severe gastroenteritis in children. Although vaccines are implemented, rotavirus-related diarrhea still claims ~200,000 lives annually worldwide, mainly in low-income settings, pointing to a need for improved vaccine tactics. To meet such a public health need, a P24-VP8* nanoparticle displaying the glycan-binding VP8* domains, the major neutralizing antigens of rotavirus, was generated as a new type of rotavirus vaccine. We reported here our development of a P24-VP8* nanoparticle-based trivalent vaccine. First, we established a method to produce tag-free P24-VP8* nanoparticles presenting the VP8*s of P[8], P[4], and P[6] rotaviruses, respectively, which are the three predominantly circulating rotavirus P types globally. This approach consists of a chemical-based protein precipitation and an ion exchange purification, which may be scaled up for large vaccine production. All three P24-VP8* nanoparticle types self-assembled efficiently with authentic VP8*-glycan receptor binding function. After they were mixed as a trivalent vaccine, we showed that intramuscular immunization of the vaccine elicited high IgG titers specific to the three homologous VP8* types in mice. The resulted mouse sera strongly neutralized replication of all three rotavirus P types in cell culture. Thus, the trivalent P24-VP8* nanoparticles are a promising vaccine candidate for parenteral use against multiple P types of predominant rotaviruses.

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Section: Introductionmentioning

confidence: 99%

A Nanoparticle-Based Trivalent Vaccine Targeting the Glycan Binding VP8* Domains of Rotaviruses

Xia

Huang

Jiang

et al. 2021

Viruses

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“…Firstly, studies showed that the affinity of CTxB to GM1 receptors, acts as delivering moiety to the cell surface, thus increases cellular uptake efficiency and antigen presentation [29]. Secondly, the proper stability of this protein, which can even be administered orally, will increase overall protein stability [30,31]. It should be noted that the adjuvant itself, is an antigen of Vibrio cholera, so it can also induce immunization against Vibrio cholera [32,33].…”

Section: Discussionmentioning

confidence: 99%

Designing a chimeric subunit vaccine for influenza virus, based on HA2, M2e and CTxB: a bioinformatics study

Jafari

Malih

Gomari

et al. 2020

BMC Mol and Cell Biol

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Background Type A influenza viruses are contagious and even life-threatening if left untreated. So far, no broadly protective vaccine is available due to rapid antigenic changes and emergence of new subtypes of influenza virus. In this study, we exploited bioinformatics tools in order to design a subunit chimeric vaccine from the antigenic and highly conserved regions of HA and M2 proteins of H7N9 subtype of influenza virus. We used mucosal adjuvant candidates, including CTxB, STxB, ASP-1, and LTB to stimulate mucosal immunity and analyzed the combination of HA2, M2e, and the adjuvant. Furthermore, to improve the antigen function and to maintain their three-dimensional structure, 12 different linkers including six rigid linkers and six flexible linkers were used. The 3D structure model was generated using a combination of homology and ab initio modeling methods and the molecular dynamics of the model were analyzed, either. Results Analysis of different adjuvants showed that using CtxB as an adjuvant, results in higher overall vaccine stability and higher half-life among four adjuvant candidates. Fusion of antigens and the CTxB in the form of M2e-linker-CTxB-linker-HA2 has the most stability and half life compared to other combination forms. Furthermore, the KPKPKP rigid linker showed the best result for this candidate vaccine among 12 analyzed linkers. The changes in the vaccine 3D structure made by linker insertion found to be negligible, however, although small, the linker insertion between the antigens causes the structure to change slightly. Eventually, using predictive tools such as Ellipro, NetMHCpan I and II, CD4episcore, CTLpred, BepiPred and other epitope analyzing tools, we analyzed the conformational and linear epitopes of the vaccine. The solubility, proteasome cleavage sites, peptidase and potential chemical cutters, codon optimization, post translational modification were also carried out on the final vaccine. Conclusions It is concluded that M2e-Linker-CTxB-Linker-HA2 combination of chimeric vaccine retains its 3D structure and antigenicity when KPKPKP used as linker and CTxB used as adjuvant.

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“…Because the N-terminus of CTB contains the GM1–ganglioside-binding residues, and N-terminus of VP8-1 extends from globular domain and N-terminus is flexible domain of VP8-1. Thereby, it is plausible that the binding activity, antigenicity and conformation of the antigens were disrupted more in VP8-1–CTB compared with in CTB–VP8-1 ( 68 ). Similarly, for CTB–C-CPE, the N-terminus of CTB and C-terminus of C-CPE are important for their binding to their respective receptors ( 36 – 39 ).…”

Section: Discussionmentioning

confidence: 99%

Development of Adjuvant-Free Bivalent Food Poisoning Vaccine by Augmenting the Antigenicity of Clostridium perfringens Enterotoxin

et al. 2018

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Clostridium perfringens enterotoxin (CPE) is a common cause of food poisoning and hyperkalemia-associated death. Previously, we reported that fusion of pneumococcal surface protein A (PspA) to C-terminal fragment of CPE (C-CPE) efficiently bound mucosal epithelium so that PspA-specific immune responses could be provoked. In this study, we found that fusion of C-CPE with PspA augmented the antigenicity of C-CPE itself. These findings allowed us to hypothesize that fusion of C-CPE and another food poisoning vaccine act as a bivalent food poisoning vaccine. Therefore, we constructed an adjuvant-free bivalent vaccine against CPE and cholera toxin (CT), which is a major food poisoning in developing country, by genetically fusing CT B subunit to C-CPE. Because of the low antigenicity of C-CPE, immunization of mice with C-CPE alone did not induce C-CPE-specific immune responses. However, immunization with our vaccine induced both C-CPE- and CT-specific neutralizing antibody. The underlying mechanism of the augmented antigenicity of C-CPE included the activation of T cells by CTB. Moreover, neutralizing antibodies lasted for at least 48 weeks and the quality of the antibody was dependent on the binding activity of CTB–C-CPE to its receptors. These findings suggest that our fusion protein is a potential platform for the development of an adjuvant-free bivalent vaccine against CPE and CT.

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Immunogenicity and protective efficacy of rotavirus VP8*fused to cholera toxin B subunit in a mouse model

Cited by 19 publications

References 45 publications

A Nanoparticle-Based Trivalent Vaccine Targeting the Glycan Binding VP8* Domains of Rotaviruses

A Nanoparticle-Based Trivalent Vaccine Targeting the Glycan Binding VP8* Domains of Rotaviruses

Designing a chimeric subunit vaccine for influenza virus, based on HA2, M2e and CTxB: a bioinformatics study

Development of Adjuvant-Free Bivalent Food Poisoning Vaccine by Augmenting the Antigenicity of Clostridium perfringens Enterotoxin

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