A Novel Bacterium-Like Particle-Based Vaccine Displaying the SUDV Glycoprotein Induces Potent Humoral and Cellular Immune Responses in Mice

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Abstract

Sudan virus (SUDV) causes severe lethal hemorrhagic fever in humans and nonhuman primates. The most effective and economical way to protect against Sudan ebolavirus disease is prophylactic vaccination. However, there are no licensed vaccines to prevent SUDV infections. In this study, a bacterium-like particle (BLP)-based vaccine displaying the extracellular domain of the SUDV glycoprotein (eGP) was developed based on a gram-positive enhancer matrix-protein anchor (GEM-PA) surface display system. Expression of the recombinant GEM-displayed eGP (eGP-PA-GEM) was verified by Western blotting and immunofluorescence assays. The SUDV BLPs (SBLPs), which were mixed with Montanide ISA 201VG plus Poly (I:C) combined adjuvant, could induce high SUDV GP-specific IgG titers of up to 1:40,960 and robust virus-neutralizing antibody titers reached 1:460. The SBLP also elicited T-helper 1 (Th1) and T-helper 2 (Th2) cell-mediated immunity. These data indicate that the SBLP subunit vaccine has the potential to be developed into a promising candidate vaccine against SUDV infections.

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Most cited references 49

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Antibodies are necessary for rVSV/ZEBOV-GP-mediated protection against lethal Ebola virus challenge in nonhuman primates.

Andrea Marzi, Flora Engelmann, Friederike Feldmann … (2013)

Ebola viruses cause hemorrhagic disease in humans and nonhuman primates with high fatality rates. These viruses pose a significant health concern worldwide due to the lack of approved therapeutics and vaccines as well as their potential misuse as bioterrorism agents. Although not licensed for human use, recombinant vesicular stomatitis virus (rVSV) expressing the filovirus glycoprotein (GP) has been shown to protect macaques from Ebola virus and Marburg virus infections, both prophylactically and postexposure in a homologous challenge setting. However, the immune mechanisms of protection conferred by this vaccine platform remain poorly understood. In this study, we set out to investigate the role of humoral versus cellular immunity in rVSV vaccine-mediated protection against lethal Zaire ebolavirus (ZEBOV) challenge. Groups of cynomolgus macaques were depleted of CD4+ T, CD8+ T, or CD20+ B cells before and during vaccination with rVSV/ZEBOV-GP. Unfortunately, CD20-depleted animals generated a robust IgG response. Therefore, an additional group of vaccinated animals were depleted of CD4+ T cells during challenge. All animals were subsequently challenged with a lethal dose of ZEBOV. Animals depleted of CD8+ T cells survived, suggesting a minimal role for CD8+ T cells in vaccine-mediated protection. Depletion of CD4+ T cells during vaccination caused a complete loss of glycoprotein-specific antibodies and abrogated vaccine protection. In contrast, depletion of CD4+ T cells during challenge resulted in survival of the animals, indicating a minimal role for CD4+ T-cell immunity in rVSV-mediated protection. Our results suggest that antibodies play a critical role in rVSV-mediated protection against ZEBOV.

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Demonstration of safety of probiotics -- a review.

Tiina S. Salminen, Mary Collins, Graham A Wright … (1998)

Probiotics are commonly defined as viable microorganisms (bacteria or yeasts) that exhibit a beneficial effect on the health of the host when they are ingested. They are used in foods, especially in fermented dairy products, but also in pharmaceutical preparations. The development of new probiotic strains aims at more active beneficial organisms. In the case of novel microorganisms and modified organisms the question of their safety and the risk to benefit ratio have to be assessed. Lactic acid bacteria (LAB) in foods have a long history of safe use. Members of the genera Lactococcus and Lactobacillus are most commonly given generally-recognised-as-safe (GRAS) status whilst members of the genera Streptococcus and Enterococcus and some other genera of LAB contain some opportunistic pathogens. Lactic acid bacteria are intrinsically resistant to many antibiotics. In many cases resistances are not, however, transmissible, and the species are also sensitive to many clinically used antibiotics even in the case of a lactic acid bacteria- associated opportunistic infection. Therefore no particular safety concern is associated with intrinsic type of resistance. Plasmid-associated antibiotic resistance, which occasionally occurs, is another matter because of the possibility of the resistance spreading to other, more harmful species and genera. The transmissible enterococcal resistance against glycopeptide antibiotics (vancomycin and teicoplanin) is particularly noteworthy, as vancomycin is one of the last effective antibiotics left in the treatment of certain multidrug-resistant pathogens. New species and more specific strains of probiotic bacteria are constantly identified. Prior to incorporating new strains into products their efficacy should be carefully assessed, and a case by case evaluation as to whether they share the safety status of traditional food-grade organisms should be made. The current documentation of adverse effects in the literature is reviewed. Future recommendations for the safety of already existing and new probiotics will be given.

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Ebola virus-like particle-based vaccine protects nonhuman primates against lethal Ebola virus challenge.

Kelly Warfield, Dana Swenson, Gene G. Olinger … (2007)

Currently, there are no licensed vaccines or therapeutics for the prevention or treatment of infection by the highly lethal filoviruses, Ebola virus (EBOV) and Marburg virus (MARV), in humans. We previously had demonstrated the protective efficacy of virus-like particle (VLP)-based vaccines against EBOV and MARV infection in rodents. To determine the efficacy of vaccination with Ebola VLPs (eVLPs) in nonhuman primates, we vaccinated cynomolgus macaques with eVLPs containing EBOV glycoprotein (GP), nucleoprotein (NP), and VP40 matrix protein and challenged the macaques with 1000 pfu of EBOV. Serum samples from the eVLP-vaccinated nonhuman primates demonstrated EBOV-specific antibody titers, as measured by enzyme-linked immunosorbent assay, complement-mediated lysis assay, and antibody-dependent cell-mediated cytotoxicity assay. CD44+ T cells from eVLP-vaccinated macaques but not from a naive macaque responded with vigorous production of tumor necrosis factor- alpha after EBOV-peptide stimulation. All 5 eVLP-vaccinated monkeys survived challenge without clinical or laboratory signs of EBOV infection, whereas the control animal died of infection. On the basis of safety and efficacy, eVLPs represent a promising filovirus vaccine for use in humans.

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Journal ID (nlm-ta): Viruses

Journal ID (iso-abbrev): Viruses

Journal ID (publisher-id): viruses

Title: Viruses

Publisher: MDPI

ISSN (Electronic): 1999-4915

Publication date (Electronic): 11 December 2019

Publication date Collection: December 2019

Volume: 11

Issue: 12

Electronic Location Identifier: 1149

Affiliations

[1 ]College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China; xsn881222@ 123456163.com (S.X.); s12k20180101@ 123456163.com (Z.S.)

[2 ]Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, China; jcc1990512@ 123456163.com (C.J.); jin8616771@ 123456163.com (H.J.); lwj636567@ 123456163.com (W.L.); liet0706@ 123456163.com (E.L.); cengcao@ 123456hotmail.com (Z.C.); yanfh1990@ 123456gmail.com (F.Y.); Zhang_Shengnan1992@ 123456163.com (S.Z.); ch_amms@ 123456163.com (H.C.); fengna0308@ 123456126.com (N.F.); zhaoyongkun1976@ 123456126.com (Y.Z.); gaoyuwei@ 123456gmail.com (Y.G.); yst62041@ 123456163.com (S.Y.); whl831125@ 123456163.com (H.W.)

[3 ]Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China

[4 ]College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China

[5 ]College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, China

[6 ]Key Laboratory of Animal Resistant Biology of Shandong, Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal University, Jinan 250014, China; hongbinhe@ 123456sdnu.edu.cn

[7 ]Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225000, China

Author notes

[* ]Correspondence: wjzd2005@ 123456163.com (J.W.); xiaxzh@ 123456cae.cn (X.X.)

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Shengnan Xu https://orcid.org/0000-0002-1800-0741

Article

Publisher ID: viruses-11-01149

DOI: 10.3390/v11121149

PMC ID: 6950126

PubMed ID: 31835785

SO-VID: fece894b-7d9f-4abb-bb1b-0b6bf19bfec6

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

A Novel Bacterium-Like Particle-Based Vaccine Displaying the SUDV Glycoprotein Induces Potent Humoral and Cellular Immune Responses in Mice

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Abstract

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MDPI: Coronavirus

Most cited references 49

Antibodies are necessary for rVSV/ZEBOV-GP-mediated protection against lethal Ebola virus challenge in nonhuman primates.

Demonstration of safety of probiotics -- a review.

Ebola virus-like particle-based vaccine protects nonhuman primates against lethal Ebola virus challenge.

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