DOCSLIB.ORG

Enhancement of Immunogenicity of Synthetic Peptide Vaccines Related to Hepatitis in Chemically Defined Models Consisting of T- and B-Cell Epitopes

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Enhancement of Immunogenicity of Synthetic Peptide Vaccines Related to Hepatitis in Chemically Defined Models Consisting of T- and B-Cell Epitopes Proc. Natl. Acad. Sci. USA Vol. 86, pp. 9084-9088, December 1989 Biochemistry Vaccine engineering: Enhancement of immunogenicity of synthetic peptide vaccines related to hepatitis in chemically defined models consisting of T- and B-cell epitopes JAMES P. TAM* AND YI-AN Lu The Rockefeller University, 1230 York Avenue, New York, NY 10021 Communicated by Bruce Merrifield, July 10, 1989 ABSTRACT We report the development of two models for entire amino acid sequence of the S protein, an NH2-terminal synthetic hepatitis B vaccines. The models were based on the fragment, the 55-residue pre-S(2), and a 108- to 119-residue multiple antigen peptide (MAP) system and contained the pre-S(1), the length ofwhich depends on the HBV strain. The relevant B- and T-cell epitopes without any macromolecular pre-S(1) region is located upstream from the pre-S(2) region, carrier. Two peptides, representing the a determinant of the S irrespective of subtypes. The virus-neutralizing antibodies region (S protein) of hepatitis B surface antigen, a dominant are elicited by the S region ofthe HBsAg as well as the pre-(S) serotype of hepatitis B virus infection found in humans, and region of the HBV (2-4). residues 12-26 ofthe pre-S(2) region ofthe middle protein were Serologically, HBsAg has one group-specific determinant incorporated as either monoepitope or diepitope MAP models. (a) and two sets of mutually exclusive determinants (d or y Immunizations of outbred rabbits with the monoepitope MAP and w or r), giving four major serotypes (adw, ayw, adr, and that contains the pre-S(2) antigen resulted in high-titered ayr). Bhatnager et al. (5) and others (6, 7) reported that antibody response to the middle protein, but the other mono- residues 139-147 of the S protein contained an essential part epitope, containing only the a-determinant peptide antigen, of the a determinant of HBsAg. Because most anti-HB resulted in poor immune responses to either the peptide response in humans is generally directed against the common antigens or to the S protein. The diepitope MAPs containing determinant a, encountered in all serotypes of HBV, immu- both the a and the pre-S(2) determinants produced high-titer nization with one serotype of HBsAg is protective against all antibodies reactive to the a-synthetic peptide and the S protein, serotypes. Itoh et al. (8) and others (9, 10) reported that a as well as to the middle proteins. Thus, our results show that peptide of the pre-S(2) protein (residues 14-32) raised pro- the diepitope MAP models eliminate the need for a protein tective antibodies in chimpanzees. These synthetic peptides carrier and that the pre-S(2) peptide determinant serves as a were coupled to protein carriers such as keyhole limpet T-helper cell epitope that enhances the immune response of the hemocyanin for immunization. Because protein carriers are S region and overcomes the poor immunogenicity encountered undesirable for human vaccines, we have recently designed with a single epitope of the S region. a chemically defined approach known as multiple antigen peptide (MAP) system to incorporate peptide antigens that A long-term goal for the development of synthetic vaccines give a macromolecular structure without a large protein is the design of chemically unambiguous, multivalent vac- carrier (11, 12). MAPs were sufficiently immunogenic and cines containing the relevant B- and T-cell epitopes but elicit specific monoclonal and polyclonal antibodies to rec- requiring no macromolecular carrier. Such synthetic vac- ognize their cognate proteins. MAPs were also designed to cines would eliminate many irrelevant determinants of bac- allow flexibility to incorporate multiple epitopes in a chem- terial and viral vaccines that may cause undesirable side ically unambiguous system. In this study, we describe the effects. Hepatitis B virus (HBV) represents an important design oftwo chemically defined models that incorporate two target for a synthetic peptide vaccine model because it affects epitopes of HBsAg, the a determinant of the S region nearly 200 million people worldwide, and chronic infection consisting of residues 140-146, and the pre-S(2) antigen produces a risk of developing hepatocellular carcinoma (1). consisting of residues 12-26. Our results show that immuni- The development of a conventional vaccine has been hin- zation of outbred rabbits with the monoepitope models dered by the difficulty of growing HBV in tissue culture. containing only the a determinant peptide antigen produced Currently available vaccines for HBV include subviral com- no to poor immune responses to either the peptide antigen or ponents of inactivated hepatitis B surface antigen (HBsAg) to the HBsAg containing the S region, whereas the diepitope purified from plasma ofasymptomatic HBV-infected carriers models containing both the a and the pre-S(2) determinants and surface proteins obtained from the DNA recombinant produce high-titered antibodies reactive to the synthetic a method. The limitations of both vaccines include production peptide and the HBsAg, as well as to the pre-S(2) peptide costs and safety in the former case and the incomplete antigen. inclusion of all epitopes (e.g., pre-S region) in the latter case (2). A synthetic vaccine based on synthetic peptides may MATERIALS AND METHODS provide an improved design, the necessary supply, and the safety needed for an efficacious vaccine. Synthesis of MAP Containing One Epitope. The synthesis of The DNA of HBV has a large open reading frame encom- MAP was accomplished manually by a stepwise solid-phase passing 1167-1200 base pairs (3, 4). The S gene encodes for procedure (11-13) on t-butoxycarbonyl (Boc)-Ala-OCH2- the S protein, the major antigen ofthe HBsAg, which consists Pam resin (14) (0.1 mmol of alanine is present in 1 g of resin). of 226 amino acid residues. Two minor but larger envelope proteins (the middle proteins) contain, in addition to the Abbreviations: MAP, multiple antigen peptide; HBV, hepatitis B virus; HBsAg, hepatitis virus surface antigen; Boc, t-butoxycar- bonyl; Boc-Lys(Boc), Na,NE-Boc2-Lys; Fmoc, 9-fluorenylmethox- The publication costs of this article were defrayed in part by page charge ycarbonyl; Acm, acetamidomethyl; DCC, dicyclohexylcarbodiim- payment. This article must therefore be hereby marked "advertisement" ide. in accordance with 18 U.S.C. §1734 solely to indicate this fact. *To whom reprint requests should be addressed. 9084 Downloaded by guest on October 2, 2021 Biochemistry: Tam and Lu Proc. Natl. Acad. Sci. USA 86 (1989) 9085 After removal of the Boc group by 50% trifluoroacetic acid trifunctional amino acids as follows: Glu(tert-butyl ester), and neutralization of the resulting salt by diisopropylethyl- Asp(tert-butyl ester), Lys(Boc), Thr(tert-butyl ester). Depro- amine (DIEA) the synthesis of the first level of the carrier tection by piperidine was preceded by one piperidine pre- core to form [Boc-Lys(Boc)]-Ala-OCH2-Pam resin was wash, and the coupling was mediated with DCC/1-hydroxy- achieved using a 4-mol excess of Boc-Lys(Boc) via dicyclo- benzotriazole in dimethylformamide. After completion of syn- hexylcarbodiimide (DCC) alone in CH2Cl2. The second and thesis, the MAP-resin was treated with low-high HF (15) to third levels were synthesized by the same protocol to give the remove the peptide chains from the resin. The procedure for octabranching Boc-Lys(Boc) core matrix. For synthesizing Fmoc amino acid peptide chain was as follows: (i) 20 ml of the core matrix of a MAP containing two different antigen dimethylformamide (three times for 1 min); (ii) 20 ml of sequences, 9-fluorenylmethoxycarbonyl (Fmoc)-Lys(Boc) piperidine/dimethylformamide (1:1, vol/vol) (1 min); (iii) 20 was used in the third level to give Fmoc-Lys(Boc) end ml of piperidine/dimethylformamide (1:1, vol/vol) (10 min); groups. The protecting group scheme for synthesis ofantigen (iv) 20 ml ofdimethylformamide (three times for 1 min); (v) 20 was as follows: Boc group for the a-NH2 terminus and ml of CH2Cl2 (three times for 1 min); (vi) 20 ml of dimethyl- side-chain protection groups for the trifunctional amino acids formamide (two times for 1 min); (vii) amino acid (4 equiva- were: Glu(benzyl ester), Lys(p-chlorobenzyloxycarbonyl), lents) of 5 ml of dimethylformamide (5 min), 1-hydroxyben- Thr(benzyl), Asp(benzyl ester), Cys(acetamidomethyl; zotriazole (4 equivalents) in dimethylformamide, DCC (4 Acm), Arg(tosyl), and Tyr(p-bromobenzyloxycarbonyl). De- equivalents) in CH2Cl2 were added for 2 hr; (viii) 20 ml of protection by trifluoroacetic acid was preceded by one tri- dimethylformamide (four times for 2 min); (ix) 20 ml ofCH2CI2 fluoroacetic acid prewash. Neutralization by DIEA was in (two times for 2 min). dimethylformamide. The coupling was mediated with DCC/ Dimerization of Two Heterlogous Epitope MAPs by Oxida- 1-hydroxybenzotriazole in dimethylformamide. After com- tion to the Disulfide. To 1 ,umol of MAP, the diepitope pletion of the synthesis, the MAP-resin was treated with containing Cys(Acm) dissolved in a deaerated and N2- trifluoroacetic acid to remove the Na-Boc groups, then purified 50% acetic acid solution at room temperature, 500 Iul acetylated with 10%o acetic anhydride/10To DIEA in CH2CI2, of a solution of 12 in MeOH (1 mM solution) was added and finally cleaved with the low-high HF method (15) to batchwise for 1 hr at 0°C. The reaction was quenched by remove the MAP from the resin support. The crude peptide adding 1 M aqueous sodium thiosulfate until the yellow color was then washed with cold ether/mercaptoethanol (99:1 was removed. MeOH was removed by dialysis in 0.1 acetic vol/vol) to remove p-thiocresol and p-cresol and extracted acid, and the desired MAPs were purified by gel-permeation into 8 M urea in 0.1 m Tris HCI buffer (pH 8.0).
Load more

Recommended publications
  • Mrna Vaccine: a Potential Therapeutic Strategy Yang Wang† , Ziqi Zhang† , Jingwen Luo† , Xuejiao Han† , Yuquan Wei and Xiawei Wei*
    Wang et al. Molecular Cancer (2021) 20:33 https://doi.org/10.1186/s12943-021-01311-z REVIEW Open Access mRNA vaccine: a potential therapeutic strategy Yang Wang† , Ziqi Zhang† , Jingwen Luo† , Xuejiao Han† , Yuquan Wei and Xiawei Wei* Abstract mRNA vaccines have tremendous potential to fight against cancer and viral diseases due to superiorities in safety, efficacy and industrial production. In recent decades, we have witnessed the development of different kinds of mRNAs by sequence optimization to overcome the disadvantage of excessive mRNA immunogenicity, instability and inefficiency. Based on the immunological study, mRNA vaccines are coupled with immunologic adjuvant and various delivery strategies. Except for sequence optimization, the assistance of mRNA-delivering strategies is another method to stabilize mRNAs and improve their efficacy. The understanding of increasing the antigen reactiveness gains insight into mRNA-induced innate immunity and adaptive immunity without antibody-dependent enhancement activity. Therefore, to address the problem, scientists further exploited carrier-based mRNA vaccines (lipid-based delivery, polymer-based delivery, peptide-based delivery, virus-like replicon particle and cationic nanoemulsion), naked mRNA vaccines and dendritic cells-based mRNA vaccines. The article will discuss the molecular biology of mRNA vaccines and underlying anti-virus and anti-tumor mechanisms, with an introduction of their immunological phenomena, delivery strategies, their importance on Corona Virus Disease 2019 (COVID-19) and related clinical trials against cancer and viral diseases. Finally, we will discuss the challenge of mRNA vaccines against bacterial and parasitic diseases. Keywords: mRNA vaccine, Self-amplifying RNA, Non-replicating mRNA, Modification, Immunogenicity, Delivery strategy, COVID-19 mRNA vaccine, Clinical trials, Antibody-dependent enhancement, Dendritic cell targeting Introduction scientists are seeking to develop effective cancer vac- A vaccine stimulates the immune response of the body’s cines.
    [Show full text]
  • A Review of COVID-19 Vaccines in Development: 6 Months Into the Pandemic
    Article Review A review of COVID-19 vaccines in development: 6 months into the pandemic Merlin Sanicas, Melvin Sanicas, Doudou Diop, Emanuele Montomoli Corresponding author: Doudou Diop, PATH, Dakar, Sénégal. [email protected] Received: 13 Jul 2020 - Accepted: 29 Jul 2020 - Published: 05 Oct 2020 Keywords: Coronavirus, COVID-19, pandemic, vaccine development Copyright: Merlin Sanicas et al. Pan African Medical Journal (ISSN: 1937-8688). This is an Open Access article distributed under the terms of the Creative Commons Attribution International 4.0 License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Cite this article: Merlin Sanicas et al. A review of COVID-19 vaccines in development: 6 months into the pandemic. Pan African Medical Journal. 2020;37(124). 10.11604/pamj.2020.37.124.24973 Available online at: https://www.panafrican-med-journal.com/content/article/37/124/full A review of COVID-19 vaccines in development: 6 Abstract months into the pandemic 1 2 3,& The advent of the COVID-19 pandemic and the Merlin Sanicas , Melvin Sanicas , Doudou Diop , dynamics of its spread is unprecedented. 4,5 Emanuele Montomoli Therefore, the need for a vaccine against the virus is huge. Researchers worldwide are working 1Centre de Recherche en Cancérologie de around the clock to find a vaccine. Experts Marseille, Université Aix-Marseille, Marseille, 2 estimate that a fast-tracked vaccine development France, Clinical Development, Takeda process could speed a successful candidate to Pharmaceuticals International AG, Zurich, 3 4 market in approximately 12-18 months.
    [Show full text]
  • B-Cell Epitope Prediction for Peptide-Based Vaccine Design: Towards a Paradigm of Biological Outcomes for Global Health
    Caoili et al. Immunome Research 2011, 7:2:2 http://www.immunome-research.net/ RESEARCH Open Access B-cell epitope prediction for peptide-based vaccine design: towards a paradigm of biological outcomes for global health Salvador Eugenio C. Caoili Abstract Global health must address a rapidly evolving burden of disease, hence the urgent need for versatile generic technologies exemplified by peptide-based vaccines. B-cell epitope prediction is crucial for designing such vaccines; yet this approach has thus far been largely unsuccessful, prompting further inquiry into the underly- ing reasons for its apparent inadequacy. Two major obstacles to the development of B-cell epitope prediction for peptide-based vaccine design are (1) the prevailing binary classification paradigm, which mandates the problematic dichotomization of continuous outcome variables, and (2) failure to explicitly model biological consequences of immunization that are relevant to practical considerations of safety and efficacy. The first obstacle is eliminated by redefining the predictive task as quantitative estimation of empirically observable biological effects of antibody-antigen binding, such that prediction is benchmarked using measures of corre- lation between continuous rather than dichotomous variables; but this alternative approach by itself fails to address the second obstacle even if benchmark data are selected to exclusively reflect functionally relevant cross-reactivity of antipeptide antibodies with protein antigens (as evidenced by antibody-modulated protein biological activity), particularly where only antibody-antigen binding is actually predicted as a surrogate for its biological effects. To overcome the second obstacle, the prerequisite is deliberate effort to predict, a priori, biological outcomes that are of immediate practical significance from the perspective of vaccination.
    [Show full text]
  • Heterosubtypic Influenza Protection Elicited by Double-Layered
    Heterosubtypic influenza protection elicited by double- layered polypeptide nanoparticles in mice Lei Denga, Timothy Z. Changb, Ye Wanga, Song Lib, Shelly Wangc, Shingo Matsuyamaa, Guoying Yud, Richard W. Compansc, Jian-Dong Lia, Mark R. Prausnitzb, Julie A. Championb, and Bao-Zhong Wanga,1 aCenter for Inflammation, Immunity & Infection, Georgia State University Institute for Biomedical Sciences, Atlanta, GA 30303; bSchool of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332; cEmory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30307; and dState Key Laboratory of Fibrosis Biology, College of Life Science, Henan Normal University, Xinxiang, 453002 Henan, China Edited by Peter Palese, Icahn School of Medicine at Mount Sinai, New York, NY, and approved July 9, 2018 (received for review April 5, 2018) Influenza is a persistent threat to public health. Here we report required for complete protection against a lethal influenza A that double-layered peptide nanoparticles induced robust specific challenge (14). immunity and protected mice against heterosubtypic influenza A Nanotechnology provides a promising approach for the de- virus challenges. We fabricated the nanoparticles by desolvating a velopment of new generations of influenza vaccines. Physiolog- composite peptide of tandem copies of nucleoprotein epitopes into ically activated disassembling nanoparticles mimic the biophysical nanoparticles as cores and cross-linking another composite peptide of and biochemical cues of virions and initiate “danger” signals that four tandem copies of influenza matrix protein 2 ectodomain epitopes enhance the activation of innate immunity and elicit potent cellular to the core surfaces as a coating. Delivering the nanoparticles via dis- and humoral immune responses with minimal cytotoxicity (15).
    [Show full text]
  • Plant-Made HIV Vaccines and Potential Candidates
    Plant-made HIV vaccines and potential candidates Jocelyne Tremouillaux-Guiller1, Khaled Moustafa2, Kathleen Hefferon3, Goabaone Gaobotse4, and Abdullah Makhzoum4 1Faculty of Pharmaceutical Sciences, University François Rabelais, Tours, France. 2Arabic Science Archive – ArabiXiv (https://arabixiv.org). 3Department of Microbiology, Cornell University, USA. 4Department of Biological Sciences & Biotechnology, Botswana International University of Science & Technology, Botswana. Correspondence: [email protected]; [email protected] Highlights HIV/AIDS is a partially treatable but not completely curable pandemic disease. Major advances have been made to treat patients living with HIV/AIDS. Developing HIV vaccines is an ongoing endeavor and moves at an accelerated pace Plant molecular pharming is a valuable tool in HIV/AIDS vaccine research. Abstract Millions of people around the world suffer from heavy social and health burdens related to HIV/AIDS and its associated opportunistic infections. To reduce these burdens, preventive and therapeutic vaccines are required. Effective HIV vaccines have been under investigation for several decades using different animal models. Potential plant-made HIV vaccine candidates have also gained attention in the past few years. In addition to this, broadly neutralizing antibodies produced in plants which can target conserved viral epitopes and neutralize mutating HIV strains have been identified. Numerous epitopes of glycoproteins and capsid proteins of HIV-1 are a part of HIV therapy. Here, we discuss some recent findings aiming to produce anti-HIV-1 recombinant proteins in engineered plants for AIDS prophylactics and therapeutic treatments. Keywords: plant made pharmaceuticals; HIV vaccine; AIDS drug; plant molecular pharming/farming; multiepitopic HIV vaccine. 1 Introduction Acquired Immunodeficiency Syndrome (AIDS) is one of the greatest challenges to global public health today.
    [Show full text]
  • Vaccination in Developing Countries: Problems, Challenges and Opportunities - T
    GLOBAL PERSPECTIVES IN HEALTH - Vol. II - Vaccination in Developing Countries: Problems, Challenges and Opportunities - T. Pang VACCINATION IN DEVELOPING COUNTRIES: PROBLEMS, CHALLENGES, AND OPPORTUNITIES T. Pang Department of Research Policy and Cooperation, World Health Organization, Geneva, Switzerland Keywords: Developing countries, vaccination, immunization Contents 1. Introduction 2. Challenges to Improving Vaccination 3. Obstacles to Effective Vaccination 4. Solutions to Problems of Access and Coverage 5. Mechanisms: Cooperation Between Industrialized Nations and Developing Nations 6. Recent Initiatives—A Brighter Future? 6.1. The International Vaccine Institute 6.2. Global Alliance for Vaccines and Immunization 6.3. Millennium Vaccine Initiative 6.4. International AIDS Vaccine Initiative 6.5. Malaria Vaccine Initiative 7. Role of the World Health Organization 8. The Future Glossary Bibliography Biographical Sketch Summary Vaccines are the most inexpensive means of improving health and lowering morbidity and mortality caused by infectious diseases in the developing world. However, and in spite of significant advances in science and technology, the implementation of global vaccination coverage remains a pipe dream. Many obstacles and challenges remain, and imaginative and bold solutions are required. Recent initiatives based on international cooperation,UNESCO philanthropy, and goodwill – promise EOLSS a brighter future for those in need living in the developing world. 1. IntroductionSAMPLE CHAPTERS The eradication of smallpox and the imminent demise of polio are clear reminders of the power of vaccination in dealing with the scourge of communicable diseases in the developing world. The World Health Organization’s (WHO) Expanded Program for Immunization (EPI), which is focused on the six major diseases of childhood (diphtheria, pertussis, tetanus, polio, measles, and tuberculosis), succeeded in dramatically raising immunization coverage in developing countries from 5% in the 1970s to more than 80% of the birth cohort in the 1990s.
    [Show full text]
  • HIV Envelope Antigen Valency on Peptide Nanofibers
    www.nature.com/scientificreports OPEN HIV envelope antigen valency on peptide nanofbers modulates antibody magnitude and binding breadth Chelsea N. Fries1,9, Jui‑Lin Chen2,3,9, Maria L. Dennis3, Nicole L. Votaw1, Joshua Eudailey3, Brian E. Watts3, Kelly M. Hainline1, Derek W. Cain3, Richard Barfeld4, Cliburn Chan4, M. Anthony Moody3,5,6, Barton F. Haynes3,6, Kevin O. Saunders2,3,6,7, Sallie R. Permar2,3,5,6,8, Genevieve G. Fouda2,3,5* & Joel H. Collier1,6* A major challenge in developing an efective vaccine against HIV‑1 is the genetic diversity of its viral envelope. Because of the broad range of sequences exhibited by HIV‑1 strains, protective antibodies must be able to bind and neutralize a widely mutated viral envelope protein. No vaccine has yet been designed which induces broadly neutralizing or protective immune responses against HIV in humans. Nanomaterial‑based vaccines have shown the ability to generate antibody and cellular immune responses of increased breadth and neutralization potency. Thus, we have developed supramolecular nanofber‑based immunogens bearing the HIV gp120 envelope glycoprotein. These immunogens generated antibody responses that had increased magnitude and binding breadth compared to soluble gp120. By varying gp120 density on nanofbers, we determined that increased antigen valency was associated with increased antibody magnitude and germinal center responses. This study presents a proof‑of‑concept for a nanofber vaccine platform generating broad, high binding antibody responses against the HIV‑1 envelope glycoprotein. HIV-1/AIDS has been responsible for 30 million deaths since it became a global pandemic1. Despite decades of research, a vaccine against HIV-1 has remained elusive.
    [Show full text]
  • Immunity Against Mucosal Pathogens?
    What Role Does the Route of Immunization Play in the Generation of Protective Immunity against Mucosal Pathogens? This information is current as Igor M. Belyakov and Jeffrey D. Ahlers of October 3, 2021. J Immunol 2009; 183:6883-6892; ; doi: 10.4049/jimmunol.0901466 http://www.jimmunol.org/content/183/11/6883 Downloaded from References This article cites 92 articles, 38 of which you can access for free at: http://www.jimmunol.org/content/183/11/6883.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on October 3, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2009 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. What Role Does the Route of Immunization Play in the Generation of Protective Immunity against Mucosal Pathogens? Igor M. Belyakov1* and Jeffrey D. Ahlers† The route of vaccination is important in influencing im- stream, although some microorganisms are limited to the de- mune responses at the initial site of pathogen invasion velopment of disease only at the site of initial mucosal invasion where protection is most effective.
    [Show full text]
  • Potential Applications for Mrna and Peptide-Based Vaccines
    viruses Article An Epitope Platform for Safe and Effective HTLV-1-Immunization: Potential Applications for mRNA and Peptide-Based Vaccines Guglielmo Lucchese 1,*,†, Hamid Reza Jahantigh 2,3,† , Leonarda De Benedictis 2, Piero Lovreglio 2 and Angela Stufano 2,3 1 Department of Neurology, Medical University of Greifswald, 17475 Greifswald, Germany 2 Interdisciplinary Department of Medicine-Section of Occupational Medicine, University of Bari, 70124 Bari, Italy; [email protected] (H.R.J.); [email protected] (L.D.B.); [email protected] (P.L.); [email protected] (A.S.) 3 Animal Health and Zoonosis Doctoral Program, Department of Veterinary Medicine, University of Bari, 70010 Bari, Italy * Correspondence: [email protected] † These authors contributed equally to the work. Abstract: Human T-cell lymphotropic virus type 1 (HTLV-1) infection affects millions of individuals worldwide and can lead to severe leukemia, myelopathy/tropical spastic paraparesis, and numerous other disorders. Pursuing a safe and effective immunotherapeutic approach, we compared the viral polyprotein and the human proteome with a sliding window approach in order to identify oligopeptide sequences unique to the virus. The immunological relevance of the viral unique oligopeptides was assessed by searching them in the immune epitope database (IEDB). We found that Citation: Lucchese, G.; Jahantigh, HTLV-1 has 15 peptide stretches each consisting of uniquely viral non-human pentapeptides which H.R.; De Benedictis, L.; Lovreglio, P.; Stufano, A. An Epitope Platform for are ideal candidate for a safe and effective anti-HTLV-1 vaccine. Indeed, experimentally validated Safe and Effective HTLV-1 epitopes, as retrieved from the IEDB, contain peptide sequences also present in a vast number HTLV-1-Immunization: Potential of human proteins, thus potentially instituting the basis for cross-reactions.
    [Show full text]
  • The Role of Vaccines in Combatting Antimicrobial Resistance
    REVIEWS The role of vaccines in combatting antimicrobial resistance Francesca Micoli1, Fabio Bagnoli2, Rino Rappuoli 2 ✉ and Davide Serruto2 Abstract | The use of antibiotics has enabled the successful treatment of bacterial infections, saving the lives and improving the health of many patients worldwide. However, the emergence and spread of antimicrobial resistance (AMR) has been highlighted as a global threat by different health organizations, and pathogens resistant to antimicrobials cause substantial morbidity and death. As resistance to multiple drugs increases, novel and effective therapies as well as prevention strategies are needed. In this Review, we discuss evidence that vaccines can have a major role in fighting AMR. Vaccines are used prophylactically, decreasing the number of infectious disease cases, and thus antibiotic use and the emergence and spread of AMR. We also describe the current state of development of vaccines against resistant bacterial pathogens that cause a substantial disease burden both in high-income countries and in low- and medium-income countries, discuss possible obstacles that hinder progress in vaccine development and speculate on the impact of next-generation vaccines against bacterial infectious diseases on AMR. The use of antimicrobials has enabled the treatment of antibiotics, diagnostic tools, monoclonal antibodies, potentially life-threatening infections, saving the lives microbiota interventions and the use of bacteriophages and improving the health of many patients worldwide. is required to combat AMR effectively (BOx 1). However, the increasing number and global distribu- Vaccines have an unprecedented impact on human tion of drug-resistant pathogens is one of the major health7 and can be used for decades with a much lower health challenges, compromising the ability to prevent probability of resistance emergence compared with and cure a wide range of infectious diseases that were antibiotics8.
    [Show full text]
  • Neoantigen Vaccine: an Emerging Tumor Immunotherapy
    Peng et al. Molecular Cancer (2019) 18:128 https://doi.org/10.1186/s12943-019-1055-6 REVIEW Open Access Neoantigen vaccine: an emerging tumor immunotherapy Miao Peng1,2,3, Yongzhen Mo2, Yian Wang2, Pan Wu2, Yijie Zhang2, Fang Xiong2, Can Guo2,XuWu1,2, Yong Li4, Xiaoling Li2, Guiyuan Li1,2,3, Wei Xiong1,2,3 and Zhaoyang Zeng1,2,3* Abstract Genetic instability of tumor cells often leads to the occurrence of a large number of mutations, and expression of non-synonymous mutations can produce tumor-specific antigens called neoantigens. Neoantigens are highly immunogenic as they are not expressed in normal tissues. They can activate CD4+ and CD8+ T cells to generate immune response and have the potential to become new targets of tumor immunotherapy. The development of bioinformatics technology has accelerated the identification of neoantigens. The combination of different algorithms to identify and predict the affinity of neoantigens to major histocompatibility complexes (MHCs) or the immunogenicity of neoantigens is mainly based on the whole-exome sequencing technology. Tumor vaccines targeting neoantigens mainly include nucleic acid, dendritic cell (DC)-based, tumor cell, and synthetic long peptide (SLP) vaccines. The combination with immune checkpoint inhibition therapy or radiotherapy and chemotherapy might achieve better therapeutic effects. Currently, several clinical trials have demonstrated the safety and efficacy of these vaccines. Further development of sequencing technologies and bioinformatics algorithms, as well as an improvement in our understanding of the mechanisms underlying tumor development, will expand the application of neoantigen vaccines in the future. Keywords: Neoantigen, Tumor, Vaccine, Malignancy, Immunotherapy Introduction tumors [4]. Radiotherapy and chemotherapy tend to Malignant tumors are associated with high morbidity elicit tolerance and recurrence of tumor cells, resulting and mortality worldwide.
    [Show full text]
  • Towards a Universal Influenza Vaccine: Different Approaches for One Goal Giuseppe A
    Sautto et al. Virology Journal (2018) 15:17 DOI 10.1186/s12985-017-0918-y REVIEW Open Access Towards a universal influenza vaccine: different approaches for one goal Giuseppe A. Sautto1, Greg A. Kirchenbaum1 and Ted M. Ross1,2* Abstract Influenza virus infection is an ongoing health and economic burden causing epidemics with pandemic potential, affecting 5–30% of the global population annually, and is responsible for millions of hospitalizations and thousands of deaths each year. Annual influenza vaccination is the primary prophylactic countermeasure aimed at limiting influenza burden. However, the effectiveness of current influenza vaccines are limited because they only confer protective immunity when there is antigenic similarity between the selected vaccine strains and circulating influenza isolates. The major targets of the antibody response against influenza virus are the surface glycoprotein antigens hemagglutinin (HA) and neuraminidase (NA). Hypervariability of the amino acid sequences encoding HA and NA is largely responsible for epidemic and pandemic influenza outbreaks, and are the consequence of antigenic drift or shift, respectively. For this reason, if an antigenic mismatch exists between the current vaccine and circulating influenza isolates, vaccinated people may not be afforded complete protection. There is currently an unmet need to develop an effective “broadly-reactive” or “universal” influenza vaccine capable of conferring protection against both seasonal and newly emerging pre-pandemic strains. A number of novel influenza vaccine approaches are currently under evaluation. One approach is the elicitation of an immune response against the “Achille’s heel” of the virus, i.e. conserved viral proteins or protein regions shared amongst seasonal and pre- pandemic strains.
    [Show full text]