scholarly journals Designing a Construct of Chimeric Multi-Epitopes Protein for Contraceptive Vaccine in Mice: An Immunoinformatics and In Silico Study

2020 ◽  
Vol 8 (2) ◽  
pp. 71-82
Author(s):  
Behnam Mortazavi ◽  
◽  
Najaf Allahyari Fard ◽  
Farid Heidari ◽  
Ali Asghar Karkhaneh ◽  
...  
Keyword(s):  
Immune System ◽  
Fusion Protein ◽  
Solvent Accessibility ◽  
Contraceptive Effect ◽  
Contraceptive Vaccine ◽  
In Silico Study ◽  
Productive Potential ◽  
Contraceptive Vaccines ◽  
Sperm Antigens ◽  
Epitope Vaccines

Background: Contraceptive vaccines (CVs) can be used as a valuable and alternative method for the prevention of gestation in humans and animals. These vaccines can have several targets, such as superficial sperm proteins. Vaccines based on sperm antigens are quite efficacious to create a contraceptive effect. However, multi-epitope vaccines are more effective in stimulating the immune system and producing more antibodies to reduce the infertility rate. Materials and Methods: This study aimed to design and evaluate a chimeric fusion protein containing IZUMO, SACA3, and PH-20 epitopes. IZUMO1, SACA3, and PH-20 were assessed, and appropriate regions were selected using various bioinformatics tools, including IEDB, I-TASSER, ProtParam, Asa-View, and Chimera software. Protein epitopes were selected based on various characters, including specificity, solvent accessibility, their weight and length, antigenic intensity, and topology. Epitopes with high antigenic potential were selected and joined together by linkers. The designed fusion protein was simulated using Molecular Dynamic, GROMACS 5, and Chimera 1.14 software. Results: The results demonstrated that all antigenic plots and availability of epitopes in the new construct remained constant. The spermatic antigens were combined using rigid linkers as a new construct and showed a stable formation with proper solvent accessibility validated by ProSA-web and PROCHECK. Also, comparing the new structure with its original one did not show any structural change. Conclusion: Based on bioinformatics results, the fusion protein that consists of three spermatic antigens has productive potential to stimulate the immune system and capable of producing more antibodies in circulation and reliable infertility.

Sperm antigens and immunocontraception

1995 ◽  
Vol 7 (4) ◽  
pp. 825 ◽  
Author(s):  
LE Kerr
Keyword(s):  
Monoclonal Antibodies ◽  
World Population ◽  
Contraceptive Vaccine ◽  
The World ◽  
Specific Antigens ◽  
Population Crisis ◽  
Sperm Antigens

The development of novel forms of contraception is one way in which the world population crisis is being tackled. The concept of a contraceptive vaccine based on gamete-specific antigens is a particularly attractive approach. Much research has been carried out to identify sperm antigens which could be used as the immunogen. The most encouraging leads have come from groups using monoclonal antibodies to identify and characterize sperm antigens important for fertility (e.g. SP-10, PH-20 and PH-30). Identification of these molecules will also enable the development of specific tests for the diagnosis of immune infertility.

scholarly journals Construction of Recombinant Lactococcus lactis Strain Expressing VP1 Fusion Protein of Duck Hepatitis A Virus Type 1 and Evaluation of Its Immune Effect

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1479
Author(s):  
Xiaoting Zhang ◽  
Ruihua Zhang ◽  
Jingyu Wang ◽  
Nana Sui ◽  
Guige Xu ◽  
...  
Keyword(s):  
Immune System ◽  
Fusion Protein ◽  
Lactococcus Lactis ◽  
Virus Type ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Interleukin 2 ◽  
Interleukin 4 ◽  
Duck Hepatitis

With the continuous development of duck farming and the increasing breeding density, the incidence of duck hepatitis A virus type 1 (DHAV-1) has been on the rise, seriously endangering the development of duck farming. To reduce the use of antibiotics in duck breeding, susceptibility risks and mortality, and avoid virulence recovery and immune failure risk, this study aims to develop a new type of mucosal immune probiotics and make full use of molecular biology techniques, on the level of genetic engineering, to modify Lactococcus lactis (L. lactis). In this study, a secretory recombinant L. lactis named MG1363-VP1 with an enhanced Green Fluorescent Protein (eGFP) and translation enhancer T7g10L was constructed, which could express the VP1-eGFP fusion protein of DHAV-1. The animal experiment in ducklings was performed to detect the immune response and protection effect of oral microecologics by recombinant L. lactis. The results showed that oral L. lactis MG1363-VP1 significantly induced the body’s humoral immune system and mucosal immune system to produce specific anti-VP1 IgG antibodies and mucosal secretory immunoglobulin A (sIgA) for DHAV-1 in ducklings, and cytokines including interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-10 (IL-10), and interferon gamma (IFN-γ). The mortality rate was monitored simultaneously by the natural infestation in the process of production and breeding; notably, the ducklings vaccinated with L. lactis MG1363-VP1 were effectively protected against the nature infection of DHAV-1. The recombinant L. lactis MG1363-VP1 constructed in this study provides a new means of preventing and controlling DHAV-1 infection in the future.

Immunocontraception in rodents: a review of the development of a sperm-based immunocontraceptive vaccine for the grey squirrel (Sciurus carolinensis)

1997 ◽  
Vol 9 (1) ◽  
pp. 125 ◽  
Author(s):  
H. D. M. Moore ◽  
N. M. Jenkins ◽  
C. Wong
Keyword(s):  
Oral Immunization ◽  
Laboratory Animals ◽  
Sciurus Carolinensis ◽  
Wild Rodents ◽  
Grey Squirrel ◽  
Vitro Fertilization ◽  
Contraceptive Vaccine ◽  
Population Turnover ◽  
Contraceptive Vaccines

The strategy for developing contraceptive vaccines for wild rodents will depend on the species. In rats and mice, high all-year birth rates, high levels of dispersal and promiscous mating systems suggest that, if immunocontraception was used alone, >90% of the population would have to sterilized to achieve the desired control. In Britain, the grey squirrel (Sciurus carolinensis) may be a better candidate to investigate the feasibility of a contraceptive vaccine in rodents. This introduced species is a seasonal breeder with a much lower population turnover than rats or mice. As well as causing damage to woodland, it has ousted the native red squirrel (S. valgaris) from most of the UK. A humane and selective method for the control of grey squirrels is therefore highly desirable Numerous sperm-specific antigens have been identified on rodent spermatozoa. Monoclonal antibodies to particular components block sperm–egg interactions in laboratory animals and cross-react with grey squirrel spermatozoa. In vitro fertilization assays indicate that squirrel sperm–egg binding may be inhibited also. Currently, a cDNA library obtained from grey squirrel testis is being screened to identify genes encoding specific sperm antigens involved in fertilization. Methods of enhancing immunogenicity after oral immunization using microparticle carriers and immune-stimulating complexes are currently under investigation.

scholarly journals Flea-Borne Transmission Model To Evaluate Vaccine Efficacy against Naturally Acquired Bubonic Plague

2004 ◽  
Vol 72 (4) ◽  
pp. 2052-2056 ◽  
Author(s):  
Clayton O. Jarrett ◽  
Florent Sebbane ◽  
Jeffrey J. Adamovicz ◽  
Gerard P. Andrews ◽  
B. Joseph Hinnebusch
Keyword(s):  
Immune System ◽  
Fusion Protein ◽  
Vaccine Efficacy ◽  
Systemic Infection ◽  
Transmission Model ◽  
Serological Testing ◽  
Protein Vaccine ◽  
Bubonic Plague ◽  
Unvaccinated Control ◽  
New Vaccines

ABSTRACT A flea-to-mouse transmission model was developed for use in testing new candidate vaccines for the ability to protect against flea-borne plague. The model was used to evaluate a recombinant fusion protein vaccine consisting of the Yersinia pestis F1 and V antigens. After one to three challenges with Y. pestis-infected fleas, 14 of 15 unvaccinated control mice developed plague, with an average septicemia level of 9.2 × 108 Y. pestis CFU/ml. None of 15 vaccinated mice developed the disease after similar challenges, and serological testing indicated that transmitted bacteria were eliminated by the immune system before extensive replication and systemic infection could occur. The transmission and development of disease in control mice correlated with the number of bites by blocked fleas but not with the total number of fleabites. The model provides a means to directly assess the efficacy of new vaccines to prevent naturally acquired bubonic plague and to study events at the vector-host interface that lead to dissemination and disease.

scholarly journals Analysis of the contribution of the globin and reductase domains to the ligand-binding properties of bacterial haemoglobins

2007 ◽  
Vol 407 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Judith Farrés ◽  
Susanna Burckhardt-Herold ◽  
Jan Scherrer ◽  
Alexander D. Frey ◽  
Pauli T. Kallio
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Fusion Protein ◽  
Ligand Binding ◽  
Rate Constants ◽  
Ralstonia Eutropha ◽  
Solvent Accessibility ◽  
Truncated Form ◽  
Binding Properties ◽  
Reductase Domain

Bacterial Hbs (haemoglobins), like VHb (Vitreoscilla sp. Hb), and flavoHbs (flavohaemoglobins), such as FHP (Ralstonia eutropha flavoHb), have different autoxidation and ligand-binding rates. To determine the influence of each domain of flavoHbs on ligand binding, we have studied the kinetic ligand-binding properties of oxygen, carbon monoxide and nitric oxide to the chimaeric proteins, FHPg (truncated form of FHP comprising the globin domain alone) and VHb-Red (fusion protein between VHb and the C-terminal reductase domain of FHP) and compared them with those of their natural counterparts, FHP and VHb. Moreover, we also analysed polarity and solvent accessibility to the haem pocket of these proteins. The rate constants for the engineered proteins, VHb-Red and FHPg, do not differ significantly from those of their natural counterparts, VHb and FHP respectively. Our results suggest that the globin domain structure controls the reactivity towards oxygen, carbon monoxide and nitric oxide. The presence or absence of a reductase domain does not affect the affinity to these ligands.

Suppression of Inhibitor Formation Against Factor VIII in Hemophilia A Mice by Oral Delivery of Bioencapsulated Antigen

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 14-14 ◽  
Author(s):  
Roland W Herzog ◽  
Dheeraj Verma ◽  
Xiaomei Wang ◽  
Alexandra Sherman ◽  
Shina Lin ◽  
...  
Keyword(s):  
Immune System ◽  
Fusion Protein ◽  
Factor Viii ◽  
Replacement Therapy ◽  
Immune Tolerance ◽  
Blot Analysis ◽  
Oral Delivery ◽  
Plant Material ◽  
Hemophilia A ◽  
Tolerance Induction

Abstract Abstract 14 Approximately 25% of hemophilia A patients develop inhibitors against factor VIII during replacement therapy by infusion of factor VIII concentrates, rendering this treatment ineffective. Elimination of this antibody response is currently achieved by highly expensive immune tolerance induction (ITI) protocols involving prolonged administration of FVIII. No prophylactic immune tolerance protocols are available. To overcome these limitations, this study seeks to develop a cost-effective approach for tolerance induction by oral delivery of human factor VIII (hF.VIII) immunogenic domains expressed in chloroplasts and bioencapsulated in plant cells. Previously, we have shown that this approach effectively suppresses inhibitor formation and anaphylaxis against factor IX in hemophilia B mice (PNAS 107:7101, 2010). Bioencapsulation protects protein antigens from gastric enzymes and acidic environment of the stomach, resulting in antigen release to the immune system via digestion of plant cell walls by microbes that colonizing the gut. The transplastomic tobacco plants created expressed the heavy chain (HC, A1-A2), A3 and C2 domains fused to the transmucosal carrier cholera toxin B subunit (CTB) to facilitate GM1 receptor mediated delivery. Besides a GPGP hinge, a furin cleavage site was introduced to link CTB with the different domains of hF.VIII coding sequence for proper folding and release of hF.VIII domains into the circulatory or immune system. PCR and/or Southern blot analysis was carried out to confirm site-specific transgene integration. Western blot analysis showed expected size fusion protein band in all four transplastomic lines expressing CTB-HC, CTB-A2, CTB-A3 and CTB-C2 fusion protein. The GM1-ganglioside receptor binding ELISA assay with chloroplast synthesized CTB-C2 and CTB-A2 fusion protein showed equivalent absorbance when compared to the purified CTB, confirming the correct folding and disulfide-bond formation of CTB pentamers within transformed chloroplasts. Transplastomic leaves expressed CTB-HC, CTB-A2, CTB-A3 and CTB-C2 in the range of 0.4–1.4%, 0.1–0.2%, 0.3–0.7% and 3.0–9.1% in the total leaf protein. Leaf materials were ground in liquid nitrogen and orally delivered to male hemophilia A mice (C57BL6/129 F8e16 −/−) for tolerance induction. In a first set of experiments, 125 mg plant material was used per oral dose, representing a mix of an approximately equal amount of HC-CTB and C2-CTB fusion proteins. Gavages were performed twice per week for 8 weeks. Control mice were fed with wild-type plant material. During the last 4 weeks, all mice (n=6 per group) were additionally treated with recombinant B domain deleted human F.VIII (intravenous injection of 1 IU once per week). By the end of the experiment, control mice had formed IgG2a (up to 0.9 μg/ml) and IgG2b (up to 1.7 μg/ml) titers against hFVIII, which were undetectable in hF.VIII-fed mice. Moreover, the control mice formed very high-titer IgG1 against hF.VIII (ranging from 7–24 μg/ml), resulting in an inhibitor titer of up to 400 BU (with an average of 211±126 BU). In contrast, hFVIII-fed mice only developed 1.9±0.6 μg/ml IgG1 and 30±12 BU, representing a highly significant (P=0.006 and P=0.001, respectively) 7–10 fold reduction in antibody formation upon factor replacement therapy. These data demonstrate that hF.VIII antigen can be produced by transplastomic technology and provide first proof-of-principle that oral delivery of bioencapsulated hF.VIII antigen is effective in controlling inhibitor development. Current work focuses on further optimization, and generation of an edible crop plant (lettuce) expressing hFVIII domains in the chloroplast for future translational studies is well on its way. Disclosures: Daniell: Bayer: Research Funding.

scholarly journals Role of Antisperm Antibodies in Infertility, Pregnancy, and Potential forContraceptive and Antifertility Vaccine Designs: Research Progress and Pioneering Vision

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 116 ◽  
Author(s):  
A. S. ◽  
Dhama ◽  
Chakraborty ◽  
Samad ◽  
Latheef ◽  
...  
Keyword(s):  
Reproductive Tract ◽  
Research Progress ◽  
Contributory Factor ◽  
Vaginal Mucosa ◽  
Obstructive Azoospermia ◽  
Antisperm Antibodies ◽  
Contraceptive Vaccines ◽  
Sperm Antigens ◽  
And Gender

Sperm of humans, non-human primates, and other mammalian subjects is considered to be antigenic. The effect of changes in autoimmunity on reproductive cells such as spermatozoa and oocytes play a critical but indistinct role in fertility. Antisperm antibodies (ASAs) are invariably present in both females and males. However, the degree of ASA occurrence may vary according to individual and gender. Although the extent of infertility due to ASAs alone is yet to be determined, it has been found in almost 9–12% of patients who are infertile due to different causes. Postcoital presence of spermatozoa in the reproductive tract of women is not a contributory factor in ASA generation. However, ASA generation may be induced by trauma to the vaginal mucosa, or by anal or oral sex resulting in the deposition of sperm inside the digestive tract. It is strongly believed that, in humans and other species, at least some antibodies may bind to sperm antigens, causing infertility. This form of infertility is termed as immunological infertility, which may be accompanied by impairment of fertility, even in individuals with normozoospermia. Researchers target ASAs for two major reasons: (i) to elucidate the association between ASAs and infertility, the reason ASAs causes infertility, and the mechanism underlying ASA-mediated infertility; and (ii) to assess the potential of ASAs as a contraceptive in humans in case ASAs influences infertility. Therefore, this review explores the potential application of ASAs in the development of anti-spermatozoa vaccines for contraceptive purposes. The usefulness of ASAs for diagnosing obstructive azoospermia, salpingitis, and oligoasthenoteratozoospermia has been reviewed extensively. Important patents pertaining to potential candidates for spermatozoa-derived vaccines that may be utilized as contraceptives are discussed in depth. Antifertility vaccines, as well as treatments for ASA-related infertility, are also highlighted. This review will address many unresolved issues regarding mechanisms involving ASAs in the diagnosis, as well as prognoses, of male infertility. More documented scientific reports are cited to support the mechanisms underlying the potential role of ASA in infertility. The usefulness of sperm antigens or ASAs (recombinant) in human and wild or captive animal contraceptive vaccines has been revealed through research but is yet to be validated via clinical testing.

Sign in / Sign up

Export Citation Format

Share Document