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Immunoprophylaxis and Therapy Commons

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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.


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.


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 ...


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 ...


Pre-Exposure Prophylaxis With Ospa-Specific Human Monoclonal Antibodies Protects Mice Against Tick Transmission Of Lyme Disease Spirochetes, Yang Wang, Aurélie Kern, Naomi Boatright, Zachary Schiller, Andrew Sadowski, Monir Ejemel, Colby A. Souders, Keith A. Reimann, Linden Hu, William D. Thomas 2016 University of Massachusetts Medical School

Pre-Exposure Prophylaxis With Ospa-Specific Human Monoclonal Antibodies Protects Mice Against Tick Transmission Of Lyme Disease Spirochetes, Yang Wang, Aurélie Kern, Naomi Boatright, Zachary Schiller, Andrew Sadowski, Monir Ejemel, Colby A. Souders, Keith A. Reimann, Linden Hu, William D. Thomas

UMass Center for Clinical and Translational Science Research Retreat

Background. Tick transmission of Borrelia spirochetes to humans results in significant morbidity from Lyme disease worldwide. Serum concentrations of antibodies against outer surface protein A (OspA) were shown to correlate with protection from infection with Borrelia burgdorferi, the primary cause of Lyme disease in the United States.

Methods. Mice transgenic for human immunoglobulin genes were immunized with OspA protein of B. burgdorferi to generate human monoclonal antibodies (HuMabs) against OspA. HuMabs were generated and tested in in vitro borreliacidal assays and animal protection assays.

Results. Nearly 100 unique OspA specific HuMabs were generated and four HuMabs (221-7, 857-2, 319-44, and ...


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 ...


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 ...


Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez 2016 Augustana College, Rock Island Illinois

Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez

Biology: Student Scholarship & Creative Works

ABSTRACT: The HIV-1 pandemic continues to thrive due to ineffective HIV-1 vaccines. Historically, the world’s most infectious diseases, such as polio and smallpox, have been eradicated or have come close to eradication due to the advent of effective vaccines. Highly active antiretroviral therapy is able to delay the onset of AIDS but can neither rid the body of HIV-1 proviral DNA nor prevent further transmission. A prophylactic vaccine that prevents the various mechanisms HIV-1 has to evade and attack our immune system is needed to end the HIV-1 pandemic. Recent advances in engineered nuclease systems, like the CRISPR/Cas9 ...


A Cgas-Independent Sting/Irf7 Pathway Mediates The Immunogenicity Of Dna Vaccines, John Suschak, Shixia Wang, Katherine Fitzgerald, Shan Lu 2016 University of Massachusetts Medical School

A Cgas-Independent Sting/Irf7 Pathway Mediates The Immunogenicity Of Dna Vaccines, John Suschak, Shixia Wang, Katherine Fitzgerald, Shan Lu

Katherine A. Fitzgerald

It has been known since the discovery of DNA vaccines > 20 y ago that DNA vaccines can function as adjuvants. Our recent study reported the involvement of Aim2 as the sensor of DNA vaccines in eliciting Ag-specific Ab responses. Our findings indicated the presence of previously unrecognized innate immune response pathways in addition to the TLR9 pathway, which is mainly activated by the CpG motifs of DNA vaccines. Our data further demonstrated the requirement of type I IFN in DNA vaccine-induced immune responses via the Aim2 pathway, but the exact downstream molecular mechanism was not characterized. In the present study ...


Cpg Improves Influenza Vaccine Efficacy In Young Adult But Not Aged Mice, Alejandor Ramirez, Mary Dawn T. Co, Anuja Mathew 2016 University of Massachusetts Medical School

Cpg Improves Influenza Vaccine Efficacy In Young Adult But Not Aged Mice, Alejandor Ramirez, Mary Dawn T. Co, Anuja Mathew

Open Access Articles

Several studies have shown a reduced efficacy of influenza vaccines in the elderly compared to young adults. In this study, we evaluated the immunogenicity and protective efficacy of a commercially available inactivated influenza vaccine (Fluzone(R)) in young adult and aged mice. C57/BL6 mice were administered a single or double immunization of Fluzone(R) with or without CpG and challenged intranasally with H1N1 A/California/09 virus. A double immunization of Fluzone(R) adjuvanted with CpG elicited the highest level of protection in young adult mice which was associated with increases in influenza specific IgG, elevated HAI titres, reduced ...


T-Cell Immunity To Influenza In Older Adults: A Pathophysiological Framework For Development Of More Effective Vaccines, Janet E. McElhaney, George A. Kuchel, Xin Zhou, Susan L. Swain, Laura Haynes 2016 University of Connecticut School of Medicine

T-Cell Immunity To Influenza In Older Adults: A Pathophysiological Framework For Development Of More Effective Vaccines, Janet E. Mcelhaney, George A. Kuchel, Xin Zhou, Susan L. Swain, Laura Haynes

Open Access Articles

One of the most profound public health consequences of immune senescence is reflected in an increased susceptibility to influenza and other acute respiratory illnesses, as well as a loss of influenza vaccine effectiveness in older people. Common medical conditions and mental and psychosocial health issues as well as degree of frailty and functional dependence accelerate changes associated with immune senescence. All contribute to the increased risk for complications of influenza infection, including pneumonias, heart diseases, and strokes that lead to hospitalization, disability, and death in the over 65 population. Changes in mucosal barrier mechanisms and both innate and adaptive immune ...


A Balance Between Inhibitor Binding And Substrate Processing Confers Influenza Drug Resistance, Li Jiang, Ping Liu, Claudia Bank, Nicholas Renzette, Kristina Prachanronarong, L. Yilmaz, Daniel Caffrey, Konstantin Zeldovich, Celia Schiffer, Timothy Kowalik, Jeffrey Jensen, Robert Finberg, Jennifer Wang, Daniel Bolon 2016 University of Massachusetts Medical School

A Balance Between Inhibitor Binding And Substrate Processing Confers Influenza Drug Resistance, Li Jiang, Ping Liu, Claudia Bank, Nicholas Renzette, Kristina Prachanronarong, L. Yilmaz, Daniel Caffrey, Konstantin Zeldovich, Celia Schiffer, Timothy Kowalik, Jeffrey Jensen, Robert Finberg, Jennifer Wang, Daniel Bolon

Celia A. Schiffer

The therapeutic benefits of the neuraminidase (NA) inhibitor oseltamivir are dampened by the emergence of drug resistance mutations in influenza A virus (IAV). To investigate the mechanistic features that underlie resistance, we developed an approach to quantify the effects of all possible single-nucleotide substitutions introduced into important regions of NA. We determined the experimental fitness effects of 450 nucleotide mutations encoding positions both surrounding the active site and at more distant sites in an N1 strain of IAV in the presence and absence of oseltamivir. NA mutations previously known to confer oseltamivir resistance in N1 strains, including H275Y and N295S ...


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