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Immunodominant T cell

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https://www.readbyqxmd.com/read/28819024/trastuzumab-increases-her2-uptake-and-cross-presentation-by-dendritic-cells
#1
Victor A Gall, Anne V Philips, Na Qiao, Karen Clise-Dwyer, Alexander A Perakis, Mao Zhang, Guy Travis Clifton, Pariya Sukhumalchandra, Qing Ma, Sangeetha M Reddy, Dihua Yu, Jeffrey J Molldrem, George E Peoples, Gheath Alatrash, Elizabeth A Mittendorf
Early phase clinical trials evaluating CD8+ T cell-eliciting, HER2-derived peptide vaccines administered to HER2-positive breast cancer patients in the adjuvant setting suggest synergy between the vaccines and trastuzumab, the monoclonal antibody targeting the HER2 protein. Among 60 patients enrolled on clinical trials evaluating the E75+GM-CSF and GP2+GM-CSF vaccines, there have been no recurrences in patients vaccinated after receiving trastuzumab as part of standard therapy in the per treatment analyses conducted after a median follow-up of greater than 34 months...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28794283/metabolic-and-immune-effects-of-immunotherapy-with-proinsulin-peptide-in-human-new-onset-type-1-diabetes
#2
Mohammad Alhadj Ali, Yuk-Fun Liu, Sefina Arif, Danijela Tatovic, Hina Shariff, Vivienne B Gibson, Norkhairin Yusuf, Roman Baptista, Martin Eichmann, Nedyalko Petrov, Susanne Heck, Jennie H M Yang, Timothy I M Tree, Irma Pujol-Autonell, Lorraine Yeo, Lucas R Baumard, Rachel Stenson, Alex Howell, Alison Clark, Zoe Boult, Jake Powrie, Laura Adams, Florence S Wong, Stephen Luzio, Gareth Dunseath, Kate Green, Alison O'Keefe, Graham Bayly, Natasha Thorogood, Robert Andrews, Nicola Leech, Frank Joseph, Sunil Nair, Susan Seal, HoYee Cheung, Craig Beam, Robert Hills, Mark Peakman, Colin M Dayan
Immunotherapy using short immunogenic peptides of disease-related autoantigens restores immune tolerance in preclinical disease models. We studied safety and mechanistic effects of injecting human leukocyte antigen-DR4(DRB1*0401)-restricted immunodominant proinsulin peptide intradermally every 2 or 4 weeks for 6 months in newly diagnosed type 1 diabetes patients. Treatment was well tolerated with no systemic or local hypersensitivity. Placebo subjects showed a significant decline in stimulated C-peptide (measuring insulin reserve) at 3, 6, 9, and 12 months versus baseline, whereas no significant change was seen in the 4-weekly peptide group at these time points or the 2-weekly group at 3, 6, and 9 months...
August 9, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28780192/a-novel-hpv-prophylactic-peptide-vaccine-designed-by-immunoinformatics-and-structural-vaccinology-approaches
#3
Manica Negahdaripour, Mahboobeh Eslami, Navid Nezafat, Nasim Hajighahramani, Mohammad Bagher Ghoshoon, Eskandar Shoolian, Ali Dehshahri, Nasrollah Erfani, Mohammad Hossein Morowvat, Younes Ghasemi
Human papillomavirus (HPV)-caused cervical cancer is the fourth common female cancer globally. Despite availability of three effective vaccines in market, development of HPV prophylactic vaccines is still pursued due to affordability issues and type-restricted protection of the marketed vaccines. Investigational second generation prophylactic HPV vaccines are mostly exploiting epitopes from the virus minor capsid protein (L2), which despite many advantages suffer from low immunogenicity, a common problem of epitope vaccines...
August 2, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28774560/a-novel-nanoemulsion-vaccine-induces-mucosal-interleukin-17-responses-and-confers-protection-upon-mycobacterium-tuberculosis-challenge-in-mice
#4
Mushtaq Ahmed, Douglas M Smith, Tarek Hamouda, Javier Rangel-Moreno, Ali Fattom, Shabaana A Khader
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) is contracted via aerosol infection, typically affecting the lungs. Mycobacterium bovis bacillus Calmette-Guerin (BCG) is the only licensed vaccine and has variable efficacy in protecting against pulmonary TB. Additionally, chemotherapy is associated with low compliance contributing to development of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb. Thus, there is an urgent need for the design of more effective vaccines against TB...
July 31, 2017: Vaccine
https://www.readbyqxmd.com/read/28769561/nanoparticle-orientationally-displayed-antigen-epitopes-improve-neutralizing-antibody-level-in-a-model-of-porcine-circovirus-type-2
#5
Peiyang Ding, Teng Zhang, Yafei Li, Man Teng, Yaning Sun, Xiao Liu, Shujun Chai, Enmin Zhou, Qianyue Jin, Gaiping Zhang
Recent advancements in biotechnology have enabled the rapid identification and subsequent expression of pathogenic microbial major antigens that induce protective immune responses. However, subunit vaccines have not been successfully commercialized mainly due to the lack of sufficient levels of neutralizing antibodies (NAs). High levels of NA rely on the efficient recognition and cross-linking of multiple neutralizing epitopes with B-cell receptors (BCRs). Nanoparticles are able to display coupled antigenic arrays at high density and provide multiple binding molecular scenarios with BCRs...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28768877/immunodominance-of-adenovirus-derived-cd8-t-cell-epitopes-interferes-with-the-induction-of-transgene-specific-immunity-in-adenovirus-based-immunization
#6
Dominik Schöne, Camilla Patrizia Hrycak, Sonja Windmann, Dennis Lapuente, Ulf Dittmer, Matthias Tenbusch, Wibke Bayer
Adenovirus (Ad)-based immunization is a popular approach in vaccine development, and Ad-based vectors are renowned for their potential to induce strong CD8(+) T cell responses to the encoded transgene. Surprisingly, we found before in the mouse Friend retrovirus (FV) model that Ad-based immunization did not induce CD8(+) T cell responses to the FV Leader-Gag-derived immunodominant epitope GagL85-93 We show now that induction of GagL85-93-specific CD8(+) T cells was highly effective when Leader-Gag was delivered by plasmid DNA immunization, implying a role for Ad-derived epitopes in mediating unresponsiveness...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28756481/biologically-relevant-conformational-features-of-linear-and-cyclic-proteolipid-protein-plp-peptide-analogues-obtained-by-high-resolution-nuclear-magnetic-resonance-and-molecular-dynamics
#7
Golfo G Kordopati, Haralambos Tzoupis, Anastassios N Troganis, Gerasimos M Tsivgoulis, Simona Golic Grdadolnik, Carmen Simal, Theodore V Tselios
Proteolipid protein (PLP) is one of the main proteins of myelin sheath that are destroyed during the progress of multiple sclerosis (MS). The immunodominant PLP139-151 epitope is known to induce experimental autoimmune encephalomyelitis (EAE, animal model of MS), wherein residues 144 and 147 are recognized by T cell receptor (TCR) during the formation of trimolecular complex with peptide-antigen and major histocompability complex. The conformational behavior of linear and cyclic peptide analogues of PLP, namely PLP139-151 and cyclic (139-151) (L(144), R(147)) PLP139-151, have been studied in solution by means of nuclear magnetic resonance (NMR) methods in combination with unrestrained molecular dynamics simulations...
July 29, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28751821/immunomodulation-of-ra-patients-pbmc-with-a-multiepitope-peptide-derived-from-citrullinated-autoantigens
#8
Smadar Gertel, Gidi Karmon, Sivan Vainer, Ora Shovman, Martin Cornillet, Guy Serre, Yehuda Shoenfeld, Howard Amital
Citrullinated peptides are used for measuring anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). Accumulation of citrullinated proteins in the inflamed synovium suggests that they may be good targets for inducing peripheral tolerance. In view of the multiplicity of citrullinated autoantigens described as ACPA targets, we generated a multiepitope citrullinated peptide (Cit-ME) from the sequences of major citrullinated autoantigens: filaggrin, β-fibrinogen, vimentin, and collagen type II...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28751567/the-adamts13-1239-1253-peptide-is-a-dominant-hla-dr1-restricted-cd4-t-cell-epitope
#9
Laurent Gilardin, Sandrine Delignat, Ivan Peyron, Mathieu Ing, Yu-Chun Lone, Bagirath Gangadharan, Baptiste Michard, Yousra Kherabi, Meenu Sharma, Anastas Pashov, Jean-Baptiste Latouche, Mohamad Hamieh, Olivier Toutirais, Pascale Loiseau, Lionel Galicier, Agnès Veyradier, Srini Kaveri, Bernard Maillère, Paul Coppo, Sébastien Lacroix-Desmazes
Acquired thrombotic thrombocytopenic purpura is a rare and severe disease characterized by auto-antibodies directed against "A Disintegrin And Metalloproteinase with Thrombospondin type 1 repeats, 13th member" (ADAMTS13), a plasma protein involved in hemostasis. The implication of CD4+ T cells in the pathogenesis of the disease is suggested by the IgG isotype of the antibodies. However, the nature of the CD4+ T-cell epitopes remains poorly characterized. Here, we determined the HLA-DR-restricted CD4+ T-cell epitopes of ADAMTS13...
July 27, 2017: Haematologica
https://www.readbyqxmd.com/read/28738289/germinal-center-enhancement-by-extended-antigen-availability
#10
REVIEW
Kimberly M Cirelli, Shane Crotty
Vaccine elicitation of protective antibody responses has proved difficult for a number of important human pathogens, including HIV-1. The amount of somatic hypermutation associated with the development of broadly neutralizing antibodies against HIV has not been achieved using conventional immunization strategies. An underexplored aspect of vaccine design is modulation of antigen kinetics. Immunization strategies with extended antigen availability have recently been shown to enhance humoral responses. In this review, we explore the mechanisms through which sustained antigen availability can enhance germinal center responses and the potency of antibody responses...
July 21, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28724769/stlv-1-infection-of-papio-anubis-tax-sequence-heterogeneity-and-t-cell-recognition
#11
James M Termini, Diogo M Magnani, Helen S Maxwell, William Lauer, Iris Castro, Jerilyn Pecotte, Glen N Barber, David I Watkins, Ronald C Desrosiers
Natural infection of baboons with simian T lymphotropic virus (STLV) is a potentially useful model system for study of vaccination against the human virus HTLV. Here we expand the number of available full-length STLV-1 baboon sequences from one to three and relate T cell responses that recognize the immunodominant Tax protein to the tax sequences present in two individual baboons. Continuously growing T cell lines were established from two baboons, 12141 and 12752. Next-generation sequencing (NGS) of complete STLV genome sequences from these lines revealed them to be closely related but distinct from each other and from the STLV-1 baboon sequence in the NCBI sequence database...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28721397/hivis-dna-or-hivisopt-dna-priming-followed-by-cmdr-vaccinia-based-boosts-induce-both-humoral-and-cellular-murine-immune-responses-to-hiv
#12
J Hinkula, S Petkov, K Ljungberg, D Hallengärd, A Bråve, M Isaguliants, T Falkeborn, S Sharma, V Liakina, M Robb, M Eller, B Moss, G Biberfeld, E Sandström, C Nilsson, K Markland, P Blomberg, B Wahren
BACKGROUND: In order to develop a more effective prophylactic HIV-1 vaccine it is important optimize the components, improve Envelope glycoprotein immunogenicity as well as to explore prime-boost immunization schedules. It is also valuable to include several HIV-1 subtype antigens representing the world-wide epidemic. METHODS: HIVIS-DNA plasmids which include Env genes of subtypes A, B and C together with Gag subtypes A and B and RTmut/Rev of subtype B were modified as follows: the Envelope sequences were shortened, codon optimized, provided with an FT4 sequence and an immunodominant region mutated...
June 2017: Heliyon
https://www.readbyqxmd.com/read/28714529/immunologic-responses-to-a-novel-dna-vaccine-targeting-human-papillomavirus-11-e6e7
#13
Julie Ahn, Shiwen Peng, Chien-Fu Hung, Richard B S Roden, Tzyy-Choou Wu, Simon R Best
OBJECTIVES/HYPOTHESIS: Recurrent respiratory papillomatosis (RRP) is a benign disease caused by human papillomavirus (HPV) types 6 and 11. Although a prophylactic vaccine against RRP is available, a therapeutic vaccine is needed to treat those already infected. The objective of our study was to design and test a DNA vaccine targeting HPV11 proteins. STUDY DESIGN: Preclinical scientific investigation. METHODS: A DNA vaccine encoding the HPV11 E6 and E7 genes linked to calreticulin (CRT) was generated...
July 17, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28701761/antigen-specific-immunotherapies-in-rheumatic-diseases
#14
REVIEW
Judit Pozsgay, Zoltán Szekanecz, Gabriella Sármay
The main goal of antigen-specific immunotherapy (ASI) in autoimmune and rheumatic diseases is to reprogramme or remove autoreactive cells and/or induce immune tolerance to self-antigens. Current therapies in these diseases either treat symptoms or slow down disease progression but are not yet curative or preventative - disease-specific treatments are urgently needed. In contrast to the nonspecific treatments in current use that induce generalized immune suppression, which is associated with several adverse effects including increased risk of infections, ASIs target a restricted subset of B cells or T cells, and thus do not compromise systemic immunity and host defence...
July 13, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28678607/hiv-env-conserved-element-dna-vaccine-alters-immunodominance-in-macaques
#15
Xintao Hu, Antonio Valentin, Margherita Rosati, Siriphan Manocheewa, Candido Alicea, Bhabadeb Chowdhury, Jenifer Bear, Kate E Broderick, Niranjan Y Sardesai, Sylvie Le Gall, James I Mullins, George N Pavlakis, Barbara K Felber
Sequence diversity and immunodominance are major obstacles in the design of an effective vaccine against HIV. HIV Env is a highly-glycosylated protein composed of 'conserved' and 'variable' regions. The latter contains immunodominant epitopes that are frequently targeted by the immune system resulting in the generation of immune escape variants. This work describes 12 regions in HIV Env that are highly conserved throughout the known HIV M Group sequences (Env CE), and are poorly immunogenic in macaques vaccinated with full-length Env expressing DNA vaccines...
July 5, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28662714/recall-t-cell-responses-to-bluetongue-virus-produce-a-narrowing-of-the-t-cell-repertoire
#16
José-Manuel Rojas, Teresa Rodríguez-Calvo, Noemí Sevilla
In most viral infections, recall T cell responses are critical for protection. The magnitude of these secondary responses can also affect the CD8 and CD4 epitope repertoire diversity. Bluetongue virus (BTV) infection in sheep elicits a T cell response that contributes to viremia control and could be relevant for cross-protection between BTV serotypes. Here, we characterized CD4(+) and CD8(+) T cell responses during primary and recall responses. During primary immune responses, both CD4(+) and CD8(+) T cell populations expanded by 14 days post-infection (dpi)...
June 29, 2017: Veterinary Research
https://www.readbyqxmd.com/read/28651002/the-n-terminal-domain-of-mycobacterium-tuberculosis-ppe17-rv1168c-protein-plays-a-dominant-role-in-inducing-antibody-responses-in-active-tb-patients
#17
Philip Raj Abraham, Niteen Pathak, Gourango Pradhan, Gaddam Sumanlatha, Sangita Mukhopadhyay
The PPE (proline-proline-glutamic acid) proteins of Mycobacterium tuberculosis are characterized by a conserved N-terminal domain of approximately 180 amino acids and variable C-terminal domain. Since last decade, these proteins have gained much importance in the serodiagnosis of tuberculosis (TB) as they act as a source of antigenic variation. We have demonstrated earlier that one of the PPE proteins PPE17 (Rv1168c) induces strong B-cell and T-cell responses in active TB disease and also displays a higher antibody titer compared to immunodominant antigens such as ESAT-6, Hsp60 and PPD...
2017: PloS One
https://www.readbyqxmd.com/read/28641561/induction-of-humoral-and-cellular-immune-responses-in-mice-by-multiepitope-vaccines-composing-of-both-t-and-b-lymphocyte-epitopes-of-mage-a3which-are-recombined-into-hbcag
#18
Qingxin Chen, Wenshu Li, Pengfei Wang, Huanyi Shao, Yujie Ding, Wenhuan Wang, Danwei Cen, Yiqi Cai, Xiangyang Xue, Lifang Zhang, Guanbao Zhu
MAGE-A3 is highly expressed in many kinds of malignant diseases, and considered to be an ideal candidate for anti-tumor vaccine. To improve the immunogenicity of epitopes of MAGE-A3, hepatitis B virus core antigen (HBcAg) was used as an immune-carrier by insertion epitopes at HBcAg major immunodominant region (HBcAg(MIR)). In present study, we designed three kinds of MAGE-A3 multiepitopes containing T and B-cell dominant epitope-rich peptides, and constructed three recombinant chimeras of HBcAg(MIR)/MAGE-A3(EPI-1), HBcAg(MIR)/MAGE-A3(EPI-2), and HBcAg(MIR)/MAGE-A3(EPI-3) with prokaryotic codon optimization...
June 20, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28618262/the-helper-t-cell-s-dilemma-in-tuberculosis
#19
Daniel L Barber
Vaccination approaches eliciting strong CD4 T cell responses provide only weak protection from tuberculosis. In this issue of Cell Host & Microbe, Moguche et al. (2017) show that T cells specific for different immunodominant vaccine antigens can fail to protect for opposite reasons, highlighting a major challenge in tuberculosis vaccine design.
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28600217/limited-genetic-diversity-in-the-global-plasmodium-vivax-cell-traversal-protein-of-ookinetes-and-sporozoites-celtos-sequences-implications-for-pvceltos-based-vaccine-development
#20
Akram Abouie Mehrizi, Fatemeh Torabi, Sedigheh Zakeri, Navid Dinparast Djadid
Cell traversal protein of Ookinetes and Sporozoites (CelTOS) is a new malaria vaccine candidate antigen. Since one of the main challenges in malaria vaccine development is the extensive antigenic diversity of this parasite, local and global gene diversity analysis is of particular importance. Therefore, in this study, the genetic diversity of pvceltos gene was investigated among Iranian P. vivax isolates (n=46) and compared with available worldwide pvceltos sequences. One synonymous (C109A) and three amino acid replacements (V118L, K178T, and G179R) were observed in Iranian pvceltos sequences in compare with Sal-1 sequence leading to five haplotypes including PvCelt-A (GSVKGL, 13%), PvCelt-B (GSLKGL, 50%), PvCelt-C (GSLTGL, 17...
June 6, 2017: Infection, Genetics and Evolution
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