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Immunoprophylaxis and Therapy Commons

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The Role Of Late Antigen In Cd4 Memory T Cell Formation During Influena [I.E. Influenza] Infection: A Dissertation, Bianca L. Bautista 2016 University of Massachusetts Medical School

The Role Of Late Antigen In Cd4 Memory T Cell Formation During Influena [I.E. Influenza] Infection: A Dissertation, Bianca L. Bautista

GSBS Dissertations and Theses

While memory CD4 T cells are critical for effective immunity to pathogens, the mechanisms underlying their generation are poorly defined. Although extensive work has been done to examine the role of antigen (Ag) in shaping memory formation, most studies focus on the requirements during the first few days of the response known as the priming phase. Little is known about whether or not Ag re-encounter by effector T cells (late Ag) alters CD4 memory T cell formation. Since influenza infection produces a large, heterogeneous, protective CD4 memory T cell population, I used this model to examine the role of late ...


Fc Receptor-Mediated Activities Of Env-Specific Monoclonal Antibodies Generated From Human Volunteers Receiving A Dna Prime-Protein Boost Hiv Vaccine: A Dissertation, Matthew R. Costa 2016 University of Massachusetts Medical School

Fc Receptor-Mediated Activities Of Env-Specific Monoclonal Antibodies Generated From Human Volunteers Receiving A Dna Prime-Protein Boost Hiv Vaccine: A Dissertation, Matthew R. Costa

GSBS Dissertations and Theses

Human immunodeficiency type 1 (HIV-1) is able to elicit broadly potent neutralizing antibodies in a very small subset of individuals only after several years’ infection and as a result, vaccines that elicit these types of antibodies have been difficult to design. The RV144 trial showed that a moderate protection is possible, which may correlate with antibody dependent cellular cytotoxicity (ADCC) activity. Previous studies in the Lu lab demonstrated that in an HIV-1 vaccine phase I trial, DP6-001, a polyvalent Env DNA prime-protein boost formulation, could elicit potent and broadly reactive, gp120-specific antibodies with positive neutralization activities along with multiple Fc ...


Pd-L1 Expression In Ebv-Negative Diffuse Large B-Cell Lymphoma: Clinicopathologic Features And Prognostic Implications, Wei Xing, Karen A. Dresser, Rui Zhang, Andrew M. Evens, Hongbo Yu, Bruce A. Woda, Benjamin J. Chen 2016 University of Massachusetts Medical School

Pd-L1 Expression In Ebv-Negative Diffuse Large B-Cell Lymphoma: Clinicopathologic Features And Prognostic Implications, Wei Xing, Karen A. Dresser, Rui Zhang, Andrew M. Evens, Hongbo Yu, Bruce A. Woda, Benjamin J. Chen

Open Access Articles

Programmed cell death ligand 1 (PD-L1) is a cell surface glycoprotein that regulates the cellular immune response and serves as a targetable immune checkpoint molecule. PD-L1 is expressed on tumor cells and the immune microenvironment of several human malignancies, including a subset of aggressive lymphomas. We sought to investigate further the clinical and pathologic features of EBV-negative diffuse large B-cell lymphoma (DLBCL) cases that express PD-L1. Immunohistochemical staining using an anti-PD-L1 monoclonal antibody was performed on DLBCL cases from 86 patients. These patients received standard chemotherapy treatment and were followed for up to 175 months. Overall, 14 cases (16%) were ...


A Model To Explain How The Bacille Calmette Guerin (Bcg) Vaccine Drives Interleukin-12 Production In Neonates, Chido Loveness Kathivu, Daniel H. Libraty 2016 University of Massachusetts Medical School

A Model To Explain How The Bacille Calmette Guerin (Bcg) Vaccine Drives Interleukin-12 Production In Neonates, Chido Loveness Kathivu, Daniel H. Libraty

Open Access Articles

The Bacille Calmette Guerin (BCG) vaccine is the only routine vaccination at birth that effectively induces neonatal T-helper 1 (Th1)-polarized immune responses. The primary cytokine that drives CD4+ T-cell Th1 differentiation is interleukin (IL)-12 p70, a heterodimeric cytokine composed of the IL-12 p35 and IL-12 p40 subunits. We therefore examined the mechanisms involved in BCG vaccine stimulation of IL-12 p35 and p40 production from human umbilical cord (neonatal) cells. We found that BCG bacilli did not upregulate IL-12 p35 mRNA production, but upregulated IL-12 p40 mRNA production in a Toll-like receptor (TLR)2-dependent manner, in human neonatal monocyte-derived ...


Human Monoclonal Antibodies To Plasmodium Falciparum Circumsporozoite Protein For Transient Passive Protection Of Malaria Travelers To Endemic Areas, Stuart Nelson, Douglas Golenbock, Ann M. Moormann, Colby A. Souders, Lisa Cavacini 2016 University of Massachusettts Medical School

Human Monoclonal Antibodies To Plasmodium Falciparum Circumsporozoite Protein For Transient Passive Protection Of Malaria Travelers To Endemic Areas, Stuart Nelson, Douglas Golenbock, Ann M. Moormann, Colby A. Souders, Lisa Cavacini

Ann M. Moormann

Plasmodium falciparum, is a protozoa that causes over 214 million cases of Malaria worldwide and the World Health Organization reported an estimated 438,000 deaths attributed to malaria in 2015. Current prevention strategies have reduced malaria cases but they are either costly, have poor efficacy or resistance has begun to develop. There is a global need for an effective pre-exposure prophylaxis treatment.

The leading Malaria vaccine candidate is RTS,S which contains a monovalent Plasmodium falciparum circumsporozoite protein (CSP). The goal of this vaccine is to induce anti-CSP antibodies that would block sporozoite invasion of hepatocytes and thereby hinder parasite ...


Recombinant Ferritin-H Induces Immunosupression In European Sea Bass Larvae (Dicentrarchus Labrax) Rather Than Immunostmulation And Protection Against Vibrio Anguillarum, Daisy Vanrompay 2016 UGhent

Recombinant Ferritin-H Induces Immunosupression In European Sea Bass Larvae (Dicentrarchus Labrax) Rather Than Immunostmulation And Protection Against Vibrio Anguillarum, Daisy Vanrompay

2nd International Conference of Fish & Shellfish Immunology

No abstract provided.


Memory Cd8+ T Cell Function During Mycobacterium Tuberculosis Infection: A Dissertation, Stephen M. Carpenter 2016 University of Massachusetts Medical School

Memory Cd8+ T Cell Function During Mycobacterium Tuberculosis Infection: A Dissertation, Stephen M. Carpenter

GSBS Dissertations and Theses

T cell vaccines against Mycobacterium tuberculosis (Mtb) and other pathogens are based on the principle that memory T cells rapidly generate effector responses upon challenge, leading to pathogen clearance. Despite eliciting a robust memory CD8+ T cell response to the immunodominant Mtb antigen TB10.4 (EsxH), we find the increased frequency of TB10.4-specific CD8+ T cells conferred by vaccination to be short-lived after Mtb challenge. To compare memory and naïve CD8+ T cell function during their response to Mtb, we track their expansions using TB10.4-specific retrogenic CD8+ T cells. We find that the primary (naïve) response outnumbers the ...


Administrated Grouper (Epinephelus Coioides) Recombinant Interleukin-6 As A Fish Immunestimulatant Via Various Administrated Routes, John Han You Lin, Wan-Ching Kuo, Ching-Chou Lin, Han-Tso Lin 2016 Department of Biotechnology and Bioindustry sciences, National Cheng Kung University

Administrated Grouper (Epinephelus Coioides) Recombinant Interleukin-6 As A Fish Immunestimulatant Via Various Administrated Routes, John Han You Lin, Wan-Ching Kuo, Ching-Chou Lin, Han-Tso Lin

2nd International Conference of Fish & Shellfish Immunology

No abstract provided.


Liposomal- And Cpg Oligodeoxynucleotide-Based Vaccine Formulations Offer Protection With Reduced Adverse Effects In Rainbow Trout, Kasper Rømer Villumsen, Dennis Christensen, Erling Olaf Koppang, Anders Miki Bojesen 2016 University of Copenhagen

Liposomal- And Cpg Oligodeoxynucleotide-Based Vaccine Formulations Offer Protection With Reduced Adverse Effects In Rainbow Trout, Kasper Rømer Villumsen, Dennis Christensen, Erling Olaf Koppang, Anders Miki Bojesen

2nd International Conference of Fish & Shellfish Immunology

No abstract provided.


Administration Of Bacterial Heat Shock Protein 70 To Induce A Protective Innate Immune Response In European Sea Bass Larvae (Dicentrarchus Labrax) Against Vibrio Anguillarum, Daisy Vanrompay 2016 UGhent

Administration Of Bacterial Heat Shock Protein 70 To Induce A Protective Innate Immune Response In European Sea Bass Larvae (Dicentrarchus Labrax) Against Vibrio Anguillarum, Daisy Vanrompay

2nd International Conference of Fish & Shellfish Immunology

No abstract provided.


Combined Effects Of Dietary Mannan Oligosaccharides And Pediococcus Acidilactici And Their Combination In Low Fish Meal And Fish Oil Diets For European Sea Bass, Dicentrarchus Labrax, Juveniles, FERNANDO RIVERO-RAMÍREZ, Silvia Torrecillas, Maria José Caballero, Alex Makol, Marisol Izquierdo, Daniel Montero 2016 ULPGC (University of Las Palmas de Gran Canaria)

Combined Effects Of Dietary Mannan Oligosaccharides And Pediococcus Acidilactici And Their Combination In Low Fish Meal And Fish Oil Diets For European Sea Bass, Dicentrarchus Labrax, Juveniles, Fernando Rivero-Ramírez, Silvia Torrecillas, Maria José Caballero, Alex Makol, Marisol Izquierdo, Daniel Montero

2nd International Conference of Fish & Shellfish Immunology

No abstract provided.


Scaffolded Antigens In Yeast Cell Particle Vaccines Provide Protection Against Systemic Polyoma Virus Infection, Donald J. Tipper, Eva Szomolanyi-Tsuda 2016 University of Massachusetts Medical School

Scaffolded Antigens In Yeast Cell Particle Vaccines Provide Protection Against Systemic Polyoma Virus Infection, Donald J. Tipper, Eva Szomolanyi-Tsuda

Open Access Articles

Background. U65, a self-aggregating peptide scaffold, traps fused protein antigens in yeast cells. Conversion to Yeast Cell Particle (YCP) vaccines by partial removal of surface mannoproteins exposes beta-glucan, mediating efficient uptake by antigen-presenting cells (APCs). YCP vaccines are inexpensive, capable of rapid large-scale production and have potential for both parenteral and oral use. Results. YCP processing by alkaline hydrolysis exposes up to 20% of the glucan but converts scaffolded antigen and internal yeast proteins into a common aggregate, preventing selective yeast protein removal. For U65-green fluorescent protein (GFP) or U65-Apolipoprotein A1 (ApoA1) subcutaneous vaccines, maximal IgG responses in mice required ...


Change In Anti- Gp120 Human Monoclonal Antibody Isotype Significantly Improves Hiv-1 Neutralization, Mark Duval, Melissa Gawron, Lisa Cavacini 2016 University of Massachusetts Medical School

Change In Anti- Gp120 Human Monoclonal Antibody Isotype Significantly Improves Hiv-1 Neutralization, Mark Duval, Melissa Gawron, Lisa Cavacini

UMass Center for Clinical and Translational Science Research Retreat

HIV vaccine efforts tend to focus on the induction of IgG neutralizing antibodies. In part, this may stem from the observations that most HIV infected individuals fail to produce significant mucosal IgA. However, this is unlike most other infections and in turn it can be argued that mucosal IgA with appropriate function and specificity may contribute significantly to the prevention of HIV transmission. To explore this, we previously isotype switched F425A1g8, an anti-HIV CD4i human monoclonal antibody that binds to epitopes exposed upon CD4 binding (CD4i) The VH and VL chains were amplified from the IgG hybridoma and inserted into ...


Identification Of Gdf-6 Blocking Antibodies As Anti-Melanoma Therapeutics, Ejemel Monir, Danielle Wisheart, Alec Gramann, Arvind Venkatesan, Mark S. Klempner, Craig J. Ceol, Yang Wang 2016 University of Massachusetts Medical School

Identification Of Gdf-6 Blocking Antibodies As Anti-Melanoma Therapeutics, Ejemel Monir, Danielle Wisheart, Alec Gramann, Arvind Venkatesan, Mark S. Klempner, Craig J. Ceol, Yang Wang

UMass Center for Clinical and Translational Science Research Retreat

Through comparative oncogenomic studies and functional analyses, we have identified the bone morphogenetic protein (BMP) factor GDF6 as a new melanoma oncogene. The secreted, carboxy-terminal portion of GDF6 is the active form that binds to cell-surface receptors to initiate BMP signaling. Targeted antibodies directed against secreted proteins are a proven therapeutic modality in several diseases.

To develop therapeutic antibodies against the active form of GDF6, we generated a panel of monoclonal antibodies. Due to the high similarity of human and mouse GDF6 proteins, the C-terminal GDF6 protein was expressed as bacterial recombinant protein with fusion tags to enhance immunogenicity. The ...


Humanized Mice For The Generation Of Hiv-1 Human Monoclonal Antibodies, Melissa Gawron, Mark Duval, Michael A. Brehm, Dale Greiner, Leonard D. Shultz, Smita Jaiswal, Sean M. McCauley, Ann Dauphin, Jeremy Luban, Lisa Cavacini 2016 University of Massachusetts Medical School

Humanized Mice For The Generation Of Hiv-1 Human Monoclonal Antibodies, Melissa Gawron, Mark Duval, Michael A. Brehm, Dale Greiner, Leonard D. Shultz, Smita Jaiswal, Sean M. Mccauley, Ann Dauphin, Jeremy Luban, Lisa Cavacini

UMass Center for Clinical and Translational Science Research Retreat

Background: Despite the length of time HIV has been wreaking havoc on its victims, improvements in the prevention and treatment of HIV are needed. Anti-retroviral therapy can be effective but is expensive and not entirely accessible for people infected in third world countries. Several promising broadly neutralizing antibodies have been isolated from infected individuals; we propose that generating antigen specific human monoclonal antibodies using humanized mice further represents a promising approach to engineer prophylactic antibodies to reduce spread and infection of HIV.

Methods: Immunodeficient mice were engrafted with fetal liver and thymus (BLT) prior to infection with different HIV isolates ...


Discovery And Development Of Human Monoclonal Antibodies To Block Rhd Alloimmunization During Pregnancy, Tushar Gupta, Melissa Gawron, Colby A. Souders, Michael A. Brehm, Dale Greiner, Leonard D. Shultz, Smita Jaiswal, Sean McCauley, Ann Dauphin, Jeremy Luban, Lisa Cavacini 2016 University of Massachusetts Medical School

Discovery And Development Of Human Monoclonal Antibodies To Block Rhd Alloimmunization During Pregnancy, Tushar Gupta, Melissa Gawron, Colby A. Souders, Michael A. Brehm, Dale Greiner, Leonard D. Shultz, Smita Jaiswal, Sean Mccauley, Ann Dauphin, Jeremy Luban, Lisa Cavacini

UMass Center for Clinical and Translational Science Research Retreat

Exposure of an Rh negative mother to red blood cells (RBCs) of an Rh positive fetus results in alloimmunization and development of anti-RhD antibodies. The anti-RhD antibodies cause hemolytic disease of the new born babies during subsequent pregnancies. Current prophylactic treatment involves polyclonal anti-RhD IgG purified from plasma of humans and is administered in approximately 20% of pregnancies. While the current prophylaxis is effective, it involves the use of human plasma and non-RhD specific antibodies, thus posing a risk of transmitting infections and undesired antibody reactions. Moreover, there is a serious scarcity of plasma donors to meet the requirement of ...


Human Monoclonal Antibodies To Plasmodium Falciparum Circumsporozoite Protein For Transient Passive Protection Of Malaria Travelers To Endemic Areas, Stuart Nelson, Douglas Golenbock, Ann M. Moormann, Colby A. Souders, Lisa Cavacini 2016 University of Massachusettts Medical School

Human Monoclonal Antibodies To Plasmodium Falciparum Circumsporozoite Protein For Transient Passive Protection Of Malaria Travelers To Endemic Areas, Stuart Nelson, Douglas Golenbock, Ann M. Moormann, Colby A. Souders, Lisa Cavacini

UMass Center for Clinical and Translational Science Research Retreat

Plasmodium falciparum, is a protozoa that causes over 214 million cases of Malaria worldwide and the World Health Organization reported an estimated 438,000 deaths attributed to malaria in 2015. Current prevention strategies have reduced malaria cases but they are either costly, have poor efficacy or resistance has begun to develop. There is a global need for an effective pre-exposure prophylaxis treatment.

The leading Malaria vaccine candidate is RTS,S which contains a monovalent Plasmodium falciparum circumsporozoite protein (CSP). The goal of this vaccine is to induce anti-CSP antibodies that would block sporozoite invasion of hepatocytes and thereby hinder parasite ...


Rational Design Of An Epitope-Based Hepatitis C Virus Vaccine, Brian G. Pierce, Elisabeth N. Boucher, Ejemel Monir, William D. Thomas, Zhiping Weng, Yan Wang 2016 University of Maryland

Rational Design Of An Epitope-Based Hepatitis C Virus Vaccine, Brian G. Pierce, Elisabeth N. Boucher, Ejemel Monir, William D. Thomas, Zhiping Weng, Yan Wang

UMass Center for Clinical and Translational Science Research Retreat

Despite improving treatment methods and therapeutic options, hepatitis C virus (HCV) remains a major global disease burden, and a vaccine would help greatly in reducing its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response, thus a vaccine must elicit an immune response toward conserved, functionally important epitopes.

Using structural data of the broadly neutralizing antibody HCV1 in complex with a conserved linear epitope from the HCV E2 protein (aa 412-423, referred to as epitope I or domain E), we performed structure-based design to generate vaccine immunogens to induce antibody responses to this epitope ...


Immune Features That Afford Protection From Clinical Disease Versus Sterilizing Immunity To Bordetella Pertussis Infection In A Nonhuman Primate Model Of Whooping Cough, Keith A. Reimann, Aaron J. Belli, Sarah Fulco, Jason M. Warfel, Rijian Wang, Lisa Cavacini, James F. Papin, Steven F. Merkel, Tod J. Merkel, Mark S. Klempner 2016 University of Massachusetts Medical School

Immune Features That Afford Protection From Clinical Disease Versus Sterilizing Immunity To Bordetella Pertussis Infection In A Nonhuman Primate Model Of Whooping Cough, Keith A. Reimann, Aaron J. Belli, Sarah Fulco, Jason M. Warfel, Rijian Wang, Lisa Cavacini, James F. Papin, Steven F. Merkel, Tod J. Merkel, Mark S. Klempner

UMass Center for Clinical and Translational Science Research Retreat

The respiratory bacterial infection caused by Bordetella pertussis (whooping cough) is the only vaccine-preventable disease whose incidence has been increasing over the last 3 decades. To better understand the resurgence of this infection, a baboon animal model of pertussis infection has been developed. Naïve baboons that recover from experimental pertussis infection are resistant both to clinical disease and to airway colonization when re-challenged. In contrast, animals vaccinated with acellular pertussis vaccine and experimentally challenged do not develop disease, but airways remain colonized for 4-6 weeks. We explored the possibility that the IgG antibody response to pertussis infection is qualitatively different ...


Identification Of Fully Human Monoclonal Antibodies Against The Adhesin Domain Of Colonizing Factor Antigen I Of Escherichia Coli, Maja Sedic, Danielle Wisheart, Monir Ejemel, Matteo Stoppato, Serena Giuntini, Eileen Barry, William D. Thomas, Mark S. Klempner, Yan Wang 2016 University of Massachusetts Medical School

Identification Of Fully Human Monoclonal Antibodies Against The Adhesin Domain Of Colonizing Factor Antigen I Of Escherichia Coli, Maja Sedic, Danielle Wisheart, Monir Ejemel, Matteo Stoppato, Serena Giuntini, Eileen Barry, William D. Thomas, Mark S. Klempner, Yan Wang

UMass Center for Clinical and Translational Science Research Retreat

Enterotoxigenic Escherichia coli (ETEC) causes significant diarrheal illness in infants in the developing world and travelers to endemic countries including military personnel. Infection of the host involves bacterial colonization of the small intestinal epithelium and toxin secretion leading to watery diarrhea. CFA/I is the most common colonizing factor antigens expressed on the surface of ETEC isolates. The CFA/I adhesin, CfaE, appears to be required for ETEC binding to human intestinal cells for colonization. Human antibodies against the binding domain of CfaE have potential to block colonization of ETEC and serve as a potent immunoprophylactic therapeutic for ETEC-related diarrhea ...


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