scholarly journals Virus-like particles displaying conserved toxin epitopes stimulate broadly reactive, polyspecific, murine antibody responses capable of snake venom recognition

2021 ◽  
Author(s):  
Stefanie K. Menzies ◽  
Charlotte A. Dawson ◽  
Edouard Crittenden ◽  
Rebecca Edge ◽  
Steven R. Hall ◽  
...  
Keyword(s):  
Specific Antibody ◽  
Antibody Responses ◽  
Core Antigen ◽  
Important Species ◽  
Virus Like Particles ◽  
Venom Toxins ◽  
Group I ◽  
First Choice ◽  
Antibody Titres ◽  
Hepatitis B Core Antigen

Abstract Antivenom is currently the first-choice treatment for snakebite envenoming. However, only a low proportion of antivenom immunoglobulins are specific to venom toxins, resulting in poor dose efficacy and potency. We sought to investigate whether linear venom epitopes displayed on virus like particles can stimulate a robust and focused antibody response capable of recognising venom toxins from diverse medically important species. Bioinformatically-designed epitopes, corresponding to predicted conserved regions of group I phospholipase A2 and three finger toxins, were engineered for display on the surface of hepatitis B core antigen virus like particles and used to immunise female CD1 mice over a 14-weeks. Antibody responses to all venom epitope virus like particles were detectable by ELISA by the end of the immunisation period, although total antibody and epitope specific antibody titres were variable against the different epitope immunogens. Immunoblots using pooled sera demonstrated recognition of various venom components in a diverse panel of six elapid venoms, representing three continents and four genera. Finally, pooled terminal sera was compared to conventional antivenom via quantitative immunoblot, and demonstrated superior recognition of lower-molecular weight elapid venom toxins. This study demonstrates proof-of-principle that virus like particles engineered to display conserved toxin linear epitopes can elicit specific antibody responses in mice which are able to recognise a geographically broad range of elapid venoms.

scholarly journals The Nature of the Attenuation of Salmonella typhimurium Strains Expressing Human Papillomavirus Type 16 Virus-Like Particles Determines the Systemic and Mucosal Antibody Responses in Nasally Immunized Mice

1999 ◽  
Vol 67 (7) ◽  
pp. 3674-3679 ◽  
Author(s):  
Jalil Benyacoub ◽  
Sally Hopkins ◽  
Alexandra Potts ◽  
Sandra Kelly ◽  
Jean-Pierre Kraehenbuhl ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Salmonella Typhimurium ◽  
Specific Antibody ◽  
Antibody Responses ◽  
Core Antigen ◽  
Human Papillomavirus Type 16 ◽  
Mucosal Antibody ◽  
Nasal Immunization ◽  
Hepatitis B Core Antigen

ABSTRACT We have recently shown by using a recombinant Salmonella typhimurium PhoPc strain in mice the feasibility of using a Salmonella-based vaccine to prevent infection by the genital human papillomavirus type 16 (HPV16). Here, we compare the HPV16-specific antibody responses elicited by nasal immunization with recombinant S. typhimurium strains harboring attenuations that, in contrast to PhoPc, are suitable for human use. For this purpose, χ4989 (Δcya Δcrp) and χ4990 [Δcya Δ(crp-cdt)] were constructed in the ATCC 14028 genetic background, and comparison was made with the isogenic PhoPc and PhoP− strains. Although the levels of expression of HPV16 virus-like particle (VLP) were similar in all strains, only PhoPc HPV16 induced sustained specific antibody responses after nasal immunization, while all strains induced high antibody responses with a single nasal immunization when an unrelated viral hepatitis B core antigen was expressed. The level of the specific antibody responses induced did not correlate with the number of recombinant bacteria surviving in various organs 2 weeks after immunization. Our data suggest that the immunogenicity of attenuated Salmonella vaccine strains does not correlate with either the number of persisting bacteria after immunization or the levels of in vitro expression of the antigen carried. Rather, the PhoPc phenotype appears to provide the unique ability inSalmonella to induce immune responses against HPV16 VLPs.

scholarly journals In silico design of a T-cell epitope vaccine candidate for parasitic helminth infection

2019 ◽  
Author(s):  
Ayat Zawawi ◽  
Ruth Forman ◽  
Hannah Smith ◽  
Iris Mair ◽  
Murtala Jibril ◽  
...  
Keyword(s):  
T Cell ◽  
In Silico ◽  
Cell Epitope ◽  
Trichuris Trichiura ◽  
Antibody Responses ◽  
Core Antigen ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Virus Like Particles ◽  
Mhc Ii

AbstractTrichuris trichiura is a parasite that infects 500 million people worldwide, leading to colitis, growth retardation and Trichuris dysentery syndrome. There are no licensed vaccines available to prevent Trichuris infection and current treatments are of limited efficacy. Trichuris infections are linked to poverty, reducing children’s educational performance and the economic productivity of adults. We employed a systematic, multi-stage process to identify a candidate vaccine against trichuriasis based on the incorporation of selected T cell epitopes into virus-like particles. We conducted a systematic review to identify the most appropriate in silico prediction tools to predict histocompatibility complex class II (MHC-II) molecule T-cell epitopes. These tools were used to identify candidate MHC-II epitopes from predicted ORFs in the Trichuris genome, selected using inclusion and exclusion criteria. Selected epitopes were incorporated into Hepatitis B core antigen virus-like particles (VLPs). A combined VLP vaccine containing four Trichuris MHC-II T-cell epitopes stimulated dendritic cells and macrophages to produce pro-inflammatory and anti-inflammatory cytokines. The VLPs were internalized and co-localized in the antigen presenting cell lysosomes. Upon challenge infection, mice vaccinated with the VLPs+T-cell epitopes showed a significantly reduced worm burden, and mounted Trichuris-specific IgM and IgG2c antibody responses. The protection of mice by VLPs+T-cell epitopes was characterised by the production of mesenteric lymph node (MLN)-derived Th2 cytokines and goblet cell hyperplasia. Collectively our data establishes that a combination of in silico genome-based CD4+ T cell epitope prediction, combined with VLP delivery, offers a promising pipeline for the development of an effective, safe and affordable helminth vaccine.Author SummaryThe soil transmitted helminth Trichuris trichiura is a major parasite in developing countries; development of a comprehensive vaccine has been elusive. Here we used a systematic approach based on in silico identification of MHC-II T cell epitopes from genome sequences, their incorporation into a virus-like particle (VLP), characterization of the assemblies and testing in an in vivo murine infection model. Animals vaccinated with a preparation of four different VLP-antigen fusions showed significant reductions in intestinal worm burdens and associated antibody responses consistent with protection. The results suggest that a pipeline based on in silico prediction of potent MHC-II T cell epitopes, followed by incorporation into VLPs, could be a strategy which enables rapid translation into a vaccine against Trichuris trichiura.

Chimeric Hepatitis B Core Antigen Particles Containing B- and Th-Epitopes of Human Papillomavirus Type 16 E7 Protein Induce Specific Antibody and T-Helper Responses in Immunised Mice

Virology ◽  
1994 ◽  
Vol 200 (2) ◽  
pp. 547-557 ◽  
Author(s):  
Robert W. Tindle ◽  
Karen Herd ◽  
Patricia Londoño ◽  
Germain J.P. Fernando ◽  
Steven N. Chatfield ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Hepatitis B ◽  
Specific Antibody ◽  
Core Antigen ◽  
T Helper ◽  
Human Papillomavirus Type 16 ◽  
Hepatitis B Core Antigen

scholarly journals Tandem Fusion of Hepatitis B Core Antigen Allows Assembly of Virus-Like Particles in Bacteria and Plants with Enhanced Capacity to Accommodate Foreign Proteins

PLoS ONE ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. e0120751 ◽  
Author(s):  
Hadrien Peyret ◽  
Annick Gehin ◽  
Eva C. Thuenemann ◽  
Donatienne Blond ◽  
Aadil El Turabi ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Core Antigen ◽  
Virus Like Particles ◽  
Tandem Fusion ◽  
Foreign Proteins ◽  
Hepatitis B Core Antigen
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