Enhanced efficacy of a multi-epitope vaccine for type A and O foot‑and-mouth disease virus by fusing multiple epitopes with Mycobacterium tuberculosis heparin-binding hemagglutinin (HBHA), a novel TLR4 agonist

Yao, Lei; Shao, Jing; Ma, Feifei; Lei, Chenglin; Chang, Huiyun; Zhang, Yongguang

doi:10.1016/j.molimm.2020.02.018

Cited by 19 publications

(12 citation statements)

References 37 publications

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“…Other Th2 responses, including IL-5, IL-4, and IL-10 secretions can efficiently eliminate pathogens from body fluids. In this study, L. lactis-TB1-Co1 enhanced Th1-as well as Th2-type responses, consistent with other studies [44,45]. This is due to the fact that Th cell epitopes are vital in the promotion of both humoral as well as cell immune responses by stimulating T cells [26,46].…”

Section: Discussionsupporting

confidence: 91%

Immune Responses to Orally Administered Recombinant Lactococcus lactis Expressing Multi-Epitope Proteins Targeting M Cells of Foot-and-Mouth Disease Virus

Zhang

et al. 2021

Viruses

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Foot and mouth disease virus (FMDV), whose transmission occurs through mucosal surfaces, can also be transmitted through aerosols, direct contact, and pollutants. Therefore, mucosal immunity can efficiently inhibit viral colonization. Since vaccine material delivery into immune sites is important for efficient oral mucosal vaccination, the M cell-targeting approach is important for effective vaccination given M cells are vital for luminal antigen influx into the mucosal lymph tissues. In this study, we coupled M cell-targeting ligand Co1 to multi-epitope TB1 of FMDV to obtain TB1-Co1 in order to improve delivery efficiency of the multi-epitope protein antigen TB1. Lactococcus lactis (L. lactis) was engineered to express heterologous antigens for applications as vaccine vehicles with the ability to elicit mucosal as well as systemic immune responses. We successfully constructed L. lactis (recombinant) with the ability to express multi-epitope antigen proteins (TB1 and TB1-Co1) of the FMDV serotype A (named L. lactis-TB1 and L. lactis-TB1-Co1). Then, we investigated the immunogenic potential of the constructed recombinant L. lactis in mice and guinea pigs. Orally administered L. lactis-TB1 as well as L. lactis-TB1-Co1 in mice effectively induced mucosal secretory IgA (SIgA) and IgG secretion, development of a strong cell-mediated immune reactions, substantial T lymphocyte proliferation in the spleen, and upregulated IL-2, IFN-γ, IL-10, and IL-5 levels. Orally administered ligand-conjugated TB1 promoted specific IgG as well as SIgA responses in systemic and mucosal surfaces, respectively, when compared to orally administered TB1 alone. Then, guinea pigs were orally vaccinated with L. lactis-TB1-Co1 plus adjuvant CpG-ODN at three different doses, L. lactis-TB1-Co1, and PBS. Animals that had been immunized with L. lactis-TB1-Co1 plus adjuvant CpG-ODN and L. lactis-TB1-Co1 developed elevated antigen-specific serum IgG, IgA, neutralizing antibody, and mucosal SIgA levels, when compared to control groups. Particularly, in mice, L. lactis-TB1-Co1 exhibited excellent immune effects than L. lactis-TB1. Therefore, L. lactis-TB1-Co1 can induce elevations in mucosal as well as systemic immune reactions, and to a certain extent, provide protection against FMDV. In conclusion, M cell-targeting approaches can be employed in the development of effective oral mucosa vaccines for FMDV.

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Section: Discussionsupporting

confidence: 91%

Immune Responses to Orally Administered Recombinant Lactococcus lactis Expressing Multi-Epitope Proteins Targeting M Cells of Foot-and-Mouth Disease Virus

Zhang

et al. 2021

Viruses

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“…The maturation of dendritic cells, HTLs, CTLs, and IFN-γ-producing cells is induced by the 50S ribosomal protein L7/L12 when naive T-cells are stimulated ( 61 ). HBHA is a novel TLR4 agonist with minimal systemic toxicity, in addition to possessing a strong immunostimulatory potential and the potential to induce dendritic cells maturation in a TLR4-dependent manner ( 92 ). Linkers are necessary for extended conformation (flexibility), protein folding, and functional domain separation, all of which help produce a more stable protein structure ( 93 ).…”

Section: Discussionmentioning

confidence: 99%

Exploring whole proteome to contrive multi-epitope-based vaccine for NeoCoV: An immunoinformtics and in-silico approach

et al. 2022

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Neo-Coronavirus (NeoCoV) is a novel Betacoronavirus (β-CoVs or Beta-CoVs) discovered in bat specimens in South Africa during 2011. The viral sequence is highly similar to Middle East Respiratory Syndrome, particularly that of structural proteins. Thus, scientists have emphasized the threat posed by NeoCoV associated with human angiotensin-converting enzyme 2 (ACE2) usage, which could lead to a high death rate and faster transmission rate in humans. The development of a NeoCoV vaccine could provide a promising option for the future control of the virus in case of human infection. In silico predictions can decrease the number of experiments required, making the immunoinformatics approaches cost-effective and convenient. Herein, with the aid of immunoinformatics and reverse vaccinology, we aimed to formulate a multi-epitope vaccine that may be used to prevent and treat NeoCoV infection. Based on the NeoCoV proteins, B-cell, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) epitopes were shortlisted. Four vaccines (Neo-1–4) were devised by fusing shortlisted epitopes with appropriate adjuvants and linkers. The secondary and three-dimensional structures of final vaccines were then predicted. The binding interactions of these potential vaccines with toll-like immune receptors (TLR-2, TLR-3, and TLR-4) and major histocompatibility complex molecules (MHC-I and II) reveal that they properly fit into the receptors’ binding domains. Besides, Neo-1 and Neo-4 vaccines exhibited better docking energies of -101.08 kcal/mol and -114.47 kcal/mol, respectively, with TLR-3 as compared to other vaccine constructs. The constructed vaccines are highly antigenic, non-allergenic, soluble, non-toxic, and topologically assessable with good physiochemical characteristics. Codon optimization and in-silico cloning confirmed efficient expression of the designed vaccines in Escherichia coli strain K12. In-silico immune simulation indicated that Neo-1 and Neo-4 vaccines could induce a strong immune response against NeoCoV. Lastly, the binding stability and strong binding affinity of Neo-1 and Neo-4 with TLR-3 receptor were validated using molecular dynamics simulations and free energy calculations (Molecular Mechanics/Generalized Born Surface Area method). The final vaccines require experimental validation to establish their safety and effectiveness in preventing NeoCoV infections.

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“…HBHA is a novel TLR4 agonist with no systemic toxicity. It has a strong immunostimulatory potential and the ability to stimulate the maturation of DCs in a TLR4-dependent manner (82). Following Robert et al ( 18), CTL and B-cell epitopes were linked together by inserting AAY and GPGPG linker.…”

Section: Discussionmentioning

confidence: 99%

Contriving multi-epitope vaccine ensemble for monkeypox disease using an immunoinformatics approach

et al. 2022

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The current global outbreak of monkeypox (MPX) disease, caused by Monkeypox virus (MPXV), has resulted in 16 thousand infection cases, five deaths, and has been declared a global health emergency of international concern by the World Health Organization. Given current challenges in the safety of existing vaccines, a vaccine to prevent MPX infection and/or onset of symptoms would significantly advance disease management. In this context, a multi-epitope-based vaccine could be a well-suited approach. Herein, we searched a publicly accessible database (Virus Pathogen Database and Analysis Resource) for MPXV immune epitopes from various antigens. We prioritized a group of epitopes (10 CD8+ T cells and four B-cell epitopes) using a computer-aided technique based on desirable immunological and physicochemical properties, sequence conservation criteria, and non-human homology. Three multi-epitope vaccines were constructed (MPXV-1–3) by fusing finalized epitopes with the aid of appropriate linkers and adjuvant (beta-defensin 3, 50S ribosomal protein L7/L12, and Heparin-binding hemagglutinin). Codon optimization and in silico cloning in the pET28a (+) expression vector ensure the optimal expression of each construct in the Escherichia Coli system. Two and three-dimensional structures of the constructed vaccines were predicted and refined. The optimal binding mode of the construct with immune receptors [Toll-like receptors (TLR2, TLR3, and TLR4)] was explored by molecular docking, which revealed high docking energies of MPXV-1–TLR3 (–99.09 kcal/mol), MPXV-2–TLR3 (–98.68 kcal/mol), and MPXV-3–TLR2 (–85.22 kcal/mol). Conformational stability and energetically favourable binding of the vaccine-TLR2/3 complexes were assessed by performing molecular dynamics simulations and free energy calculations (Molecular Mechanics/Generalized Born Surface Area method). In silico immune simulation suggested that innate, adaptive, and humoral responses will be elicited upon administration of such potent multi-epitope vaccine constructs. The vaccine constructs are antigenic, non-allergen, non-toxic, soluble, topographically exposed, and possess favourable physicochemical characteristics. These results may help experimental vaccinologists design a potent MPX vaccine.

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Enhanced efficacy of a multi-epitope vaccine for type A and O foot‑and-mouth disease virus by fusing multiple epitopes with Mycobacterium tuberculosis heparin-binding hemagglutinin (HBHA), a novel TLR4 agonist

Cited by 19 publications

References 37 publications

Immune Responses to Orally Administered Recombinant Lactococcus lactis Expressing Multi-Epitope Proteins Targeting M Cells of Foot-and-Mouth Disease Virus

Immune Responses to Orally Administered Recombinant Lactococcus lactis Expressing Multi-Epitope Proteins Targeting M Cells of Foot-and-Mouth Disease Virus

Exploring whole proteome to contrive multi-epitope-based vaccine for NeoCoV: An immunoinformtics and in-silico approach

Contriving multi-epitope vaccine ensemble for monkeypox disease using an immunoinformatics approach

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