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Immunoprophylaxis and Therapy Commons

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Identification And Characterization Of Human Monoclonal Antibodies For Immunoprophylaxis Against Enterotoxigenic Escherichia Coli Infection, Serena Giuntini, Matteo Stoppato, Maja Sedic, Ejemel Monir, Jessica R. Pondish, Danielle Wisheart, Zachary Schiller, William D. Thomas Jr., Eileen M. Barry, Lisa Cavacini, mark S. klempner, Yan Wang 2018 University of Massachusetts Medical School

Identification And Characterization Of Human Monoclonal Antibodies For Immunoprophylaxis Against Enterotoxigenic Escherichia Coli Infection, Serena Giuntini, Matteo Stoppato, Maja Sedic, Ejemel Monir, Jessica R. Pondish, Danielle Wisheart, Zachary Schiller, William D. Thomas Jr., Eileen M. Barry, Lisa Cavacini, Mark S. Klempner, Yan Wang

Open Access Articles

Background. Enterotoxigenic Escherichia coli (ETEC) cause diarrheal illness in infants in the developing world and travelers to endemic countries including military personnel. ETEC infection of the host involves colonization of the small intestinal epithelium and toxin secretion leading to watery diarrhea. There is currently no vaccine licensed to prevent ETEC. CFA/I is one of the most common colonization factor antigens (CFAs). The CFA/I adhesin subunit, CfaE, is required for ETEC adhesion to host intestinal cells. Human antibodies against CfaE have potential to block colonization of ETEC and serve as an immunoprophylactic against ETEC-related diarrhea.

Methods. Mice transgenic for ...


Pd-L1 Is Expressed On Human Platelets And Is Affected By Immune Checkpoint Therapy, Verena Rolfes, Christian Idel, Ralph Pries, Kirstin Plotze-Martin, Jens Habermann, Timo Gemoll, Sabine Bohnet, Eicke Latz, Julika Ribbat-Idel, Bernardo S. Franklin, Barbara Wollenberg 2018 University of Bonn

Pd-L1 Is Expressed On Human Platelets And Is Affected By Immune Checkpoint Therapy, Verena Rolfes, Christian Idel, Ralph Pries, Kirstin Plotze-Martin, Jens Habermann, Timo Gemoll, Sabine Bohnet, Eicke Latz, Julika Ribbat-Idel, Bernardo S. Franklin, Barbara Wollenberg

Open Access Articles

Cancer immunotherapy has been revolutionised by drugs that enhance the ability of the immune system to detect and fight tumors. Immune checkpoint therapies that target the programmed death-1 receptor (PD-1), or its ligand (PD-L1) have shown unprecedented rates of durable clinical responses in patients with various cancer types. However, there is still a large fraction of patients that do not respond to checkpoint inhibitors, and the challenge remains to find cellular and molecular cues that could predict which patients would benefit from these therapies. Using a series of qualitative and quantitative methods we show here that PBMCs and platelets from ...


Immunohistochemical Expression And Prognostic Value Of Pd-L1 In Extrapulmonary Small Cell Carcinoma: A Single Institution Experience, Mohammed Salhab, Yazan Migdady, Melanie Donahue, Yiqin Xiong, Karen A. Dresser, William Walsh, Benjamin J. Chen, James Liebmann 2018 University of Massachusetts Medical School

Immunohistochemical Expression And Prognostic Value Of Pd-L1 In Extrapulmonary Small Cell Carcinoma: A Single Institution Experience, Mohammed Salhab, Yazan Migdady, Melanie Donahue, Yiqin Xiong, Karen A. Dresser, William Walsh, Benjamin J. Chen, James Liebmann

Open Access Articles

BACKGROUND: Extrapulmonary small cell carcinomas (ESCC) are rare but aggressive tumors. Relapses are common despite treatment with chemotherapy and/or radiotherapy. Prospective data for treatment of ESCC are lacking; treatment of these cancers usually incorporates lung small cell carcinoma treatment recommendations. Cancer staging remains the most important prognostic factor. Cancer immunotherapy targeting the PD-1/PD-L1 pathway has shown efficacy in multiple tumor types, and could be an appealing treatment strategy for these rare tumors.

METHODS: We investigated PD-L1 expression by immunochemistry (IHC) in ESCCs diagnosed at University of Massachusetts Medical Center, from 1999 to 2016. 34 cases with sufficient material ...


Efficacy Of A Respiratory Syncytial Virus Vaccine Candidate In A Maternal Immunization Model, Jorge C. G. Blanco, Lioubov M. Pletneva, Lori McGinnes Cullen, Raymonde O. Otoa, Mira C. Patel, Lurds R. Fernando, Marina S. Boukhvalova, Trudy G. Morrison 2018 Sigmovir Biosystems Inc.

Efficacy Of A Respiratory Syncytial Virus Vaccine Candidate In A Maternal Immunization Model, Jorge C. G. Blanco, Lioubov M. Pletneva, Lori Mcginnes Cullen, Raymonde O. Otoa, Mira C. Patel, Lurds R. Fernando, Marina S. Boukhvalova, Trudy G. Morrison

Open Access Articles

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants. Maternal immunization is an option to increase maternal antibody levels and protect infants from infection. Here we assess the efficacy of virus-like particle (VLP) vaccine candidates containing stabilized pre-fusion (pre-F) or post-fusion (post-F) conformations of the RSV F protein and the attachment RSV G protein in a maternal immunization model using cotton rats. VLP vaccines containing RSV F and G proteins strongly boost pre-existing RSV immunity in dams preventing their perinatal drop in immunity. Boosting is stronger for the pre-F VLP than for the post-F VLP or ...


A Novel Sialylation Site On Neisseria Gonorrhoeae Lipooligosaccharide Links Heptose Ii Lactose Expression With Pathogenicity, Sanjay Ram, Sunita Gulati, Lisa A. Lewis, Srinjoy Chakraborti, Bo Zheng, Rosane B. de Oliveira, George W. Reed, Andrew D. Cox, Jianjun Li, Frank St. Michael, Jacek Stupak, Xiao-Hong Su, Sudeshna Saha, Corinna S. Landig, Ajit Varki, Peter A. Rice 2018 University of Massachusetts Medical School

A Novel Sialylation Site On Neisseria Gonorrhoeae Lipooligosaccharide Links Heptose Ii Lactose Expression With Pathogenicity, Sanjay Ram, Sunita Gulati, Lisa A. Lewis, Srinjoy Chakraborti, Bo Zheng, Rosane B. De Oliveira, George W. Reed, Andrew D. Cox, Jianjun Li, Frank St. Michael, Jacek Stupak, Xiao-Hong Su, Sudeshna Saha, Corinna S. Landig, Ajit Varki, Peter A. Rice

University of Massachusetts Medical School Faculty Publications

Sialylation of lacto-N-neotetraose (LNnT) extending from heptose I (HepI) of gonococcal lipooligosaccharide (LOS) contributes to pathogenesis. Previously, gonococcal LOS sialyltransterase (Lst) was shown to sialylate LOS in Triton X-100 extracts of strain 15253, which expresses lactose from both HepI and HepII, the minimal structure required for mAb 2C7 binding. Ongoing work has shown that growth of 15253 in cytidine monophospho-N-acetylneuraminic acid (CMP-Neu5Ac)-containing media enables binding to CD33/Siglec-3, a cell surface receptor that binds sialic acid, suggesting that lactose termini on LOS of intact gonococci can be sialylated. Neu5Ac was detected on LOSs of strains 15253 and a MS11 ...


Intron-Containing Rna From The Hiv-1 Provirus Activates Type I Interferon And Inflammatory Cytokines, Sean M. McCauley, Kyusik Kim, Anetta Nowosielska, Ann Dauphin, Leonid Yurkovetskiy, William E. Diehl, Jeremy Luban 2018 University of Massachusetts Medical School

Intron-Containing Rna From The Hiv-1 Provirus Activates Type I Interferon And Inflammatory Cytokines, Sean M. Mccauley, Kyusik Kim, Anetta Nowosielska, Ann Dauphin, Leonid Yurkovetskiy, William E. Diehl, Jeremy Luban

Program in Molecular Medicine Publications and Presentations

HIV-1-infected people who take drugs that suppress viremia to undetectable levels are protected from developing AIDS. Nonetheless, these individuals have chronic inflammation associated with heightened risk of cardiovascular pathology. HIV-1 establishes proviruses in long-lived CD4+ memory T cells, and perhaps other cell types, that preclude elimination of the virus even after years of continuous antiviral therapy. Though the majority of proviruses that persist during antiviral therapy are defective for production of infectious virions, many are expressed, raising the possibility that the HIV-1 provirus or its transcripts contribute to ongoing inflammation. Here we found that the HIV-1 provirus activated innate immune ...


Tumor Surveillance Using Liquid Biome In Pediatric High Grade Gliomas, Erin Bonner, Eshini Panditharatna, Madhuri Kambhampati, Stefaan Van Gool, Wilfried Stuecker, Roger J. Packer, Javad Nazarian 2018 Children's National Health System

Tumor Surveillance Using Liquid Biome In Pediatric High Grade Gliomas, Erin Bonner, Eshini Panditharatna, Madhuri Kambhampati, Stefaan Van Gool, Wilfried Stuecker, Roger J. Packer, Javad Nazarian

GW Research Days 2016 - Present

Immunotherapy is currently being used to treat pediatric brain cancer, though its efficacy in treating patients with diffuse intrinsic pontine glioma (DIPG), the deadliest pediatric brain tumor, has not been evaluated. MRI is the gold standard for monitoring tumor response to therapy, but is limited by pseudoresponse and psuedoprogression: post-treatment, immune cells infiltrate the primary tumor causing transient tumor enlargement, which falsely resembles tumor progression on MRI. Thus, it is critical to develop more accurate approaches to monitor tumor response to immunotherapy. Here, we use a liquid biopsy platform we have already established to monitor tumor response to therapy, to ...


New Vaccine Formulations Containing A Modified Version Of The Amastigote 2 Antigen And The Non-Virulent Trypanosoma Cruzi Cl-14 Strain Are Highly Antigenic And Protective Against Leishmania Infantum Challenge, Ana Paula M. M. Almeida, Leopoldo F.M. Machado, Daniel Doro, Frederico C. Nascimento, Leonardo Damasceno, Ricardo T. Gazzinelli, Ana Paula Fernandes, Caroline Junqueira 2018 Federal University of Minas Gerais

New Vaccine Formulations Containing A Modified Version Of The Amastigote 2 Antigen And The Non-Virulent Trypanosoma Cruzi Cl-14 Strain Are Highly Antigenic And Protective Against Leishmania Infantum Challenge, Ana Paula M. M. Almeida, Leopoldo F.M. Machado, Daniel Doro, Frederico C. Nascimento, Leonardo Damasceno, Ricardo T. Gazzinelli, Ana Paula Fernandes, Caroline Junqueira

Open Access Articles

Visceral leishmaniasis (VL) is a major public health issue reported as the second illness in mortality among all tropical diseases. Clinical trials have shown that protection against VL is associated with robust T cell responses, especially those producing IFN-gamma. The Leishmania amastigote 2 (A2) protein has been repeatedly described as immunogenic and protective against VL in different animal models; it is recognized by human T cells, and it is also commercially available in a vaccine formulation containing saponin against canine VL. Moving toward a more appropriate formulation for human vaccination, here, we tested a new optimized version of the recombinant ...


Humanized Mice In Studying Efficacy And Mechanisms Of Pd-1-Targeted Cancer Immunotherapy, Minan Wang, Michael A. Brehm, Dale L. Greiner 2018 The Jackson Laboratory

Humanized Mice In Studying Efficacy And Mechanisms Of Pd-1-Targeted Cancer Immunotherapy, Minan Wang, Michael A. Brehm, Dale L. Greiner

Open Access Articles

Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into the mechanisms underlying cancer immunotherapy. To this end, nonobese diabetic (NOD).Cg- Prkdc(scid)IL2rg(tm1Wjl)/Sz (null; NSG) mice were transplanted with human (h)CD34(+) hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patient-derived xenografts [PDX; non-small cell lung cancer (NSCLC), sarcoma, bladder cancer, and triple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft ...


Use Of Elispot Assay To Study Hbs-Specific B Cell Responses In Vaccinated And Hbv Infected Humans, Chen Tian, Yuxin Chen, Yong Liu, Shixia Wang, Yang Li, Guiyang Wang, Juan Xia, Xiang-An Zhao, Rui Huang, Shan Lu, Chao Wu 2018 Nanjing University

Use Of Elispot Assay To Study Hbs-Specific B Cell Responses In Vaccinated And Hbv Infected Humans, Chen Tian, Yuxin Chen, Yong Liu, Shixia Wang, Yang Li, Guiyang Wang, Juan Xia, Xiang-An Zhao, Rui Huang, Shan Lu, Chao Wu

Open Access Articles

Hepatitis B surface antibody (HBsAb) plays a critical role in protecting against infection of hepatitis B virus (HBV) and were extensively studied in literature. At the same time, the status of hepatitis B surface antigen (HBs)-specific B cells in both vaccinated and HBV infected people received limited attention. In the current study, we adopted a highly specific B-cell Enzyme Linked ImmunoSpot (ELISpot) assay to analyze HBs-specific B cells in various clinical settings: healthy individuals with the history of HBV vaccination before and after receiving an extra HBV vaccine boost, people chronically infected with HBV (CHB) in various clinical stages ...


Hiv-1 R5 Macrophage-Tropic Envelope Glycoprotein Trimers Bind Cd4 With High Affinity, While The Cd4 Binding Site On Non-Macrophage-Tropic, T-Tropic R5 Envelopes Is Occluded, Briana Quitadamo, Paul J. Peters, Alexander Repik, Olivia O'Connell, Zhongming Mou, Matthew Koch, Mohan Somasundaran, Robin M. Brody, Katherine Luzuriaga, Aaron Wallace, Shixia Wang, Shan Lu, Sean M. McCauley, Jeremy Luban, Maria J. Duenas-Decamp, Maria Paz Paz Gonzalez-Perez, Paul R. Clapham 2018 University of Massachusetts Medical School

Hiv-1 R5 Macrophage-Tropic Envelope Glycoprotein Trimers Bind Cd4 With High Affinity, While The Cd4 Binding Site On Non-Macrophage-Tropic, T-Tropic R5 Envelopes Is Occluded, Briana Quitadamo, Paul J. Peters, Alexander Repik, Olivia O'Connell, Zhongming Mou, Matthew Koch, Mohan Somasundaran, Robin M. Brody, Katherine Luzuriaga, Aaron Wallace, Shixia Wang, Shan Lu, Sean M. Mccauley, Jeremy Luban, Maria J. Duenas-Decamp, Maria Paz Paz Gonzalez-Perez, Paul R. Clapham

Program in Molecular Medicine Publications and Presentations

HIV-1 R5 variants exploit CCR5 as a coreceptor to infect both T cells and macrophages. R5 viruses that are transmitted or derived from immune tissue and peripheral blood are mainly inefficient at mediating infection of macrophages. In contrast, highly macrophage-tropic (mac-tropic) R5 viruses predominate in brain tissue and can be detected in cerebrospinal fluid but are infrequent in immune tissue or blood even in late disease. These mac-tropic R5 variants carry envelope glycoproteins (Envs) adapted to exploit low levels of CD4 on macrophages to induce infection. However, it is unclear whether this adaptation is conferred by an increased affinity of ...


Polymeric Peptide Mimics For Protein Delivery, Coralie Backlund 2018 University of Massachusetts Amherst

Polymeric Peptide Mimics For Protein Delivery, Coralie Backlund

Doctoral Dissertations

The plasma membrane is a major obstacle in the development and use of biomacromolecules for intracellular applications. Consequently, proteins with intracellular targets represent an enormous, yet under studied avenue for therapeutics. Extended research has aimed at facilitating intracellular delivery of exogenous proteins using protein transduction domains (PTDs), which allow transport of bioactive molecules into cells. Synthetic polymers, inspired by PTDs, provide a well-controlled platform to vary molecular architecture for structure activity relationship studies. Specifically, this thesis focuses on the use of ring-opening metathesis, a facile and efficient polymerization technique, through which we can vary structural parameters to optimize delivery of ...


Systematic Review And Meta-Analysis: Tuberculosis, Tnfα Inhibitors, And Crohn's Disease, Brent L. Cao 2018 University of Central Florida

Systematic Review And Meta-Analysis: Tuberculosis, Tnfα Inhibitors, And Crohn's Disease, Brent L. Cao

Honors in the Major Theses

Inflammation is often a protective reaction against harmful foreign agents. However, in many disease conditions, the mechanisms behind the inflammatory response are poorly understood. Often times, the inflammation causes adverse effects, such as joint pain, abdominal pain, fever, fatigue, and loss of appetite. Thus, many treatments aim to inhibit the inflammatory response in order to control adverse symptoms. Such treatments include TNFα inhibitors. However, a major risk associated with drugs inhibiting tumor necrosis factor alpha (TNFα) is serious infection, including tuberculosis (TB).

Anti-TNFα therapy is used to treat patients with Crohn’s disease, for which the risk of tuberculosis may ...


Screening Of Primary Gp120 Immunogens To Formulate The Next Generation Polyvalent Dna Prime-Protein Boost Hiv-1 Vaccines, Shixia Wang, Te-Hui Chou, Anthony Hackett, Veronica Efros, Yan Wang, Dong Han, Aaron Wallace, Yuxin Chen, Guangnan Hu, Shuying Liu, Paul R. Clapham, James Arthos, David Montefiori, Shan Lu 2017 University of Massachusetts Medical School

Screening Of Primary Gp120 Immunogens To Formulate The Next Generation Polyvalent Dna Prime-Protein Boost Hiv-1 Vaccines, Shixia Wang, Te-Hui Chou, Anthony Hackett, Veronica Efros, Yan Wang, Dong Han, Aaron Wallace, Yuxin Chen, Guangnan Hu, Shuying Liu, Paul R. Clapham, James Arthos, David Montefiori, Shan Lu

Open Access Articles

Our previous preclinical studies and a Phase I clinical trial DP6-001 have indicated that a polyvalent Env formulation was able to elicit broadly reactive antibody responses including low titer neutralizing antibody responses against viral isolates of subtypes A, B, C and AE. In the current report, a panel of 62 gp120 immunogens were screened in a rabbit model to identify gp120 immunogens that can elicit improved binding and neutralizing antibody responses and some of them can be included in the next polyvalent formulation. Only about 19% of gp120 immunogens in this panel were able to elicit neutralizing antibodies against greater ...


The Dynamics Of Immunoglobulin V-Gene Usage And Clonotype Expansion In Mice After Prime And Boost Immunizations As Analyzed By Ngs, Diego José Farfán Arribas, Shuying Liu, Shixia Wang, Shan Lu 2017 University of Massachusetts Medical School

The Dynamics Of Immunoglobulin V-Gene Usage And Clonotype Expansion In Mice After Prime And Boost Immunizations As Analyzed By Ngs, Diego José Farfán Arribas, Shuying Liu, Shixia Wang, Shan Lu

Open Access Articles

In the current study, an improved NGS approach was developed to study the B-cell repertoire evolution in a simple mouse immunization model including only two DNA immunizations. The combination of 5'RACE and Ion Torrent long reads enabled unbiased immunoglobulin repertoire analysis even from small amounts of peripheral mouse blood. The B-cell population expanded by the vaccine displayed a relatively strong clonality. Upon priming with the first vaccine dose, we observed a consistent pattern of V-segment gene and CDR3 usage (public specificities). Interestingly, this pattern diversified with the second dose of immunization -it was relatively different in individual mice in ...


The Importance Of Rsv F Protein Conformation In Vlps In Stimulation Of Neutralizing Antibody Titers In Mice Previously Infected With Rsv, Lori M. Cullen, Madelyn R. Schmidt, Trudy G. Morrison 2017 University of Massachusetts Medical School

The Importance Of Rsv F Protein Conformation In Vlps In Stimulation Of Neutralizing Antibody Titers In Mice Previously Infected With Rsv, Lori M. Cullen, Madelyn R. Schmidt, Trudy G. Morrison

Open Access Articles

Respiratory syncytial virus (RSV) is a significant respiratory pathogen but no vaccine is available. RSV infections present 2 major, unique problems. First, humans can experience repeated infections caused by the same virus sero-group indicating that protective memory responses to RSV infection are defective. Second, most people have been infected with RSV by age 5. Immune responses to these infections, while poorly protective, could impact the effectiveness of a vaccine. The goal of this study was to assess the generation of protective immune responses in mice previously infected with RSV by virus-like particle (VLP) vaccine candidates containing a stabilized pre-fusion form ...


Recombinant Subunit Vaccines For Soil-Transmitted Helminths, Jason B. Noon, Raffi V. Aroian 2017 University of Massachusetts Medical School

Recombinant Subunit Vaccines For Soil-Transmitted Helminths, Jason B. Noon, Raffi V. Aroian

Open Access Articles

Soil-transmitted helminths (STHs) collectively infect one fourth of all human beings, and the majority of livestock in the developing world. These gastrointestinal nematodes are the most important parasites on earth with regard to their prevalence in humans and livestock. Current anthelmintic drugs are losing their efficacies due to increasing drug resistance, particularly in STHs of livestock and drug treatment is often followed by rapid reinfection due to failure of the immune system to develop a protective response. Vaccines against STHs offer what drugs cannot accomplish alone. Because such vaccines would have to be produced on such a large scale, and ...


Vaccination With Recombinant Cryptococcus Proteins In Glucan Particles Protects Mice Against Cryptococcosis In A Manner Dependent Upon Mouse Strain And Cryptococcal Species, Charles A. Specht, Chrono K. Lee, Haibin Huang, Maureen M. Hester, Jianhua Liu, Bridget A. Luckie, Melanie A. Torres Santana, Zeynep Mirza, Payam Khoshkenar, Ambily Abraham, Zu T. Shen, Ali Akalin, Gary R. Ostroff, Stuart M. Levitz 2017 University of Massachusetts Medical School

Vaccination With Recombinant Cryptococcus Proteins In Glucan Particles Protects Mice Against Cryptococcosis In A Manner Dependent Upon Mouse Strain And Cryptococcal Species, Charles A. Specht, Chrono K. Lee, Haibin Huang, Maureen M. Hester, Jianhua Liu, Bridget A. Luckie, Melanie A. Torres Santana, Zeynep Mirza, Payam Khoshkenar, Ambily Abraham, Zu T. Shen, Ali Akalin, Gary R. Ostroff, Stuart M. Levitz

Open Access Articles

Development of a vaccine to protect against cryptococcosis is a priority given the enormous global burden of disease in at-risk individuals. Using glucan particles (GPs) as a delivery system, we previously demonstrated that mice vaccinated with crude Cryptococcus-derived alkaline extracts were protected against lethal challenge with Cryptococcus neoformans and Cryptococcus gattii The goal of the present study was to identify protective protein antigens that could be used in a subunit vaccine. Using biased and unbiased approaches, six candidate antigens (Cda1, Cda2, Cda3, Fpd1, MP88, and Sod1) were selected, recombinantly expressed in Escherichia coli, purified, and loaded into GPs. Three mouse ...


Vaccine-Elicited Memory Cd4+ T Cell Expansion Is Impaired In The Lungs During Tuberculosis, Stephen M. Carpenter, Jason D. Yang, Jinhee Lee, Palmira Barreira-Silva, Samuel M. Behar 2017 University of Massachusetts Medical School

Vaccine-Elicited Memory Cd4+ T Cell Expansion Is Impaired In The Lungs During Tuberculosis, Stephen M. Carpenter, Jason D. Yang, Jinhee Lee, Palmira Barreira-Silva, Samuel M. Behar

Open Access Articles

Immunological memory is the key biological process that makes vaccines possible. Although tuberculosis vaccines elicit protective immunity in animals, few provide durable protection. To understand why protection is transient, we evaluated the ability of memory CD4+ T cells to expand, differentiate, and control Mycobacterium tuberculosis. Both naive and memory CD4+ T cells initially proliferated exponentially, and the accumulation of memory T cells in the lung correlated with early bacterial control. However, later during infection, memory CD4+ T cell proliferation was curtailed and no protection was observed. We show that memory CD4+ T cells are first activated in the LN and ...


Lfa-1 Mediates Cytotoxicity And Tissue Migration Of Specific Cd8(+) T Cells After Heterologous Prime-Boost Vaccination Against Trypanosoma Cruzi Infection, Camila Pontes Ferreira, Leonardo Moro. Cariste, Fernando Dos. Santos Virgilio, Barbara Ferri Moraschi, Caroline Brandao. Monteiro, Alexandre M. Vieira Machado, Ricardo T. Gazzinelli, Oscar Bruna-Romero, Pedro Luiz. Menin Ruiz, Daniel Araki Ribeiro, Joseli Lannes-Vieira, Marcela de Freitas Lopes, Mauricio Martins Rodrigues, Jose Ronnie. de Vasconcelos Carvalho 2017 Federal University of São Paulo

Lfa-1 Mediates Cytotoxicity And Tissue Migration Of Specific Cd8(+) T Cells After Heterologous Prime-Boost Vaccination Against Trypanosoma Cruzi Infection, Camila Pontes Ferreira, Leonardo Moro. Cariste, Fernando Dos. Santos Virgilio, Barbara Ferri Moraschi, Caroline Brandao. Monteiro, Alexandre M. Vieira Machado, Ricardo T. Gazzinelli, Oscar Bruna-Romero, Pedro Luiz. Menin Ruiz, Daniel Araki Ribeiro, Joseli Lannes-Vieira, Marcela De Freitas Lopes, Mauricio Martins Rodrigues, Jose Ronnie. De Vasconcelos Carvalho

Open Access Articles

Integrins mediate the lymphocyte migration into an infected tissue, and these cells are essential for controlling the multiplication of many intracellular parasites such as Trypanosoma cruzi, the causative agent of Chagas disease. Here, we explore LFA-1 and VLA-4 roles in the migration of specific CD8(+) T cells generated by heterologous prime-boost immunization during experimental infection with T. cruzi. To this end, vaccinated mice were treated with monoclonal anti-LFA-1 and/or anti-VLA-4 to block these molecules. After anti-LFA-1, but not anti-VLA-4 treatment, all vaccinated mice displayed increased blood and tissue parasitemia, and quickly succumbed to infection. In addition, there was an ...


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