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Full-Text Articles in Medicine and Health Sciences
Characterization Of Turbo, A Tlr Ligand-Based Adjuvant For Glycoconjugate Vaccines, Kishore R. Alugupalli
Characterization Of Turbo, A Tlr Ligand-Based Adjuvant For Glycoconjugate Vaccines, Kishore R. Alugupalli
Department of Microbiology and Immunology Faculty Papers
Many bacterial polysaccharide vaccines, including the typhoid Vi polysaccharide (ViPS) and tetravalent meningococcal polysaccharide conjugate (MCV4) vaccines, do not incorporate adjuvants and are not highly immunogenic, particularly in infants. I found that endotoxin, a TLR4 ligand in ViPS, contributes to the immunogenicity of typhoid vaccines. Because endotoxin is pyrogenic, and its levels are highly variable in vaccines, I developed monophosphoryl lipid A, a nontoxic TLR4 ligand-based adjuvant named Turbo. Admixing Turbo with ViPS and MCV4 vaccines improved their immunogenicity across all ages and eliminated booster requirement. To understand the characteristics of this adjuvanticity, I compared Turbo with alum. Unlike alum, …
Design And Preclinical Evaluation Of A Universal Sars-Cov-2 Mrna Vaccine, Jane Qin, Ju Hyeong Jeon, Jiangsheng Xu, Laura Katherine Langston, Ramesh Marasini, Stephanie Mou, Brian Montoya, Carolina R Melo-Silva, Hyo Jin Jeon, Tianyi Zhu, Luis J. Sigal, Renhuan Xu, Huabin Zhu
Design And Preclinical Evaluation Of A Universal Sars-Cov-2 Mrna Vaccine, Jane Qin, Ju Hyeong Jeon, Jiangsheng Xu, Laura Katherine Langston, Ramesh Marasini, Stephanie Mou, Brian Montoya, Carolina R Melo-Silva, Hyo Jin Jeon, Tianyi Zhu, Luis J. Sigal, Renhuan Xu, Huabin Zhu
Department of Microbiology and Immunology Faculty Papers
Because of the rapid mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective vaccine against SARS-CoV-2 variants is needed to prevent coronavirus disease 2019 (COVID-19). T cells, in addition to neutralizing antibodies, are an important component of naturally acquired protective immunity, and a number of studies have shown that T cells induced by natural infection or vaccination contribute significantly to protection against several viral infections including SARS-CoV-2. However, it has never been tested whether a T cell-inducing vaccine can provide significant protection against SARS-CoV-2 infection in the absence of preexisting antibodies. In this study, we designed and evaluated …
A Single Dose Of The Deactivated Rabies-Virus Vectored Covid-19 Vaccine, Coravax, Is Highly Efficacious And Alleviates Lung Inflammation In The Hamster Model, Drishya Kurup, Christoph Wirblich, Leila Zabihi Diba, Rachael Lambert, Megan Watson, Noor Shaikh, Holly Ramage, Charalambos Solomides, Matthias J Schnell
A Single Dose Of The Deactivated Rabies-Virus Vectored Covid-19 Vaccine, Coravax, Is Highly Efficacious And Alleviates Lung Inflammation In The Hamster Model, Drishya Kurup, Christoph Wirblich, Leila Zabihi Diba, Rachael Lambert, Megan Watson, Noor Shaikh, Holly Ramage, Charalambos Solomides, Matthias J Schnell
Department of Microbiology and Immunology Faculty Papers
Without sufficient herd immunity through either vaccination or natural infection, the coronavirus disease 2019 pandemic is unlikely to be controlled. Waning immunity with the currently approved vaccines suggests the need to evaluate vaccines causing the induction of long-term responses. Here, we report the immunogenicity and efficacy of our adjuvanted single-dose Rabies-vectored SARS-CoV-2 S1 vaccine, CORAVAX, in hamsters. CORAVAX induces high SARS-CoV-2 S1-specific and virus-neutralizing antibodies (VNAs) that prevent weight loss, viral loads, disease, lung inflammation, and the cytokine storm in hamsters. We also observed high Rabies VNA titers. In summary, CORAVAX is a promising dual-antigen vaccine candidate for clinical evaluation …
April:Taci Axis Is Dispensable For The Immune Response To Rabies Vaccination., Shannon L. Haley, Evgeni P. Tzvetkov, Andrew G. Lytle, Kishore R. Alugupalli, Joseph R. Plummer, James P. Mcgettigan
April:Taci Axis Is Dispensable For The Immune Response To Rabies Vaccination., Shannon L. Haley, Evgeni P. Tzvetkov, Andrew G. Lytle, Kishore R. Alugupalli, Joseph R. Plummer, James P. Mcgettigan
Department of Microbiology and Immunology Faculty Papers
There is significant need to develop a single-dose rabies vaccine to replace the current multi-dose rabies vaccine regimen and eliminate the requirement for rabies immune globulin in post-exposure settings. To accomplish this goal, rabies virus (RABV)-based vaccines must rapidly activate B cells to secrete antibodies which neutralize pathogenic RABV before it enters the CNS. Increased understanding of how B cells effectively respond to RABV-based vaccines may improve efforts to simplify post-exposure prophylaxis (PEP) regimens. Several studies have successfully employed the TNF family cytokine a proliferation-inducing ligand (APRIL) as a vaccine adjuvant. APRIL binds to the receptors TACI and B cell …
B1b Lymphocyte-Derived Antibodies Control Borrelia Hermsii Independent Of Fcα/Μ Receptor And In The Absence Of Host Cell Contact., Matthew J. Colombo, David Abraham, Akira Shibuya, Kishore R. Alugupalli
B1b Lymphocyte-Derived Antibodies Control Borrelia Hermsii Independent Of Fcα/Μ Receptor And In The Absence Of Host Cell Contact., Matthew J. Colombo, David Abraham, Akira Shibuya, Kishore R. Alugupalli
Department of Microbiology and Immunology Faculty Papers
The critical role of IgM in controlling pathogen burden has been demonstrated in a variety of infection models. In the murine model of Borrelia hermsii infection, IgM is necessary and sufficient for the rapid clearance of bacteremia. Convalescent, but not naïve, B1b cells generate a specific IgM response against B. hermsii, but the mechanism of IgM-mediated protection is unknown. Here, we show that neither Fcα/μR, a high-affinity receptor for IgM, nor IgM-dependent complement activation is required for controlling B. hermsii. Bacteria in diffusion chambers with a pore size impermeable to cells were killed when diffusion chambers were implanted into either …
Innate And Adaptive Immunity To The Nematode Strongyloides Stercoralis In A Mouse Model., Sandra Bonne-Annee, Jessica A. Hess, David Abraham
Innate And Adaptive Immunity To The Nematode Strongyloides Stercoralis In A Mouse Model., Sandra Bonne-Annee, Jessica A. Hess, David Abraham
Department of Microbiology and Immunology Faculty Papers
Mice have been used to the study the mechanisms of protective innate and adaptive immunity to larval Strongyloides stercoralis. During primary infection, neutrophils and eosinophils are attracted by parasite components and kill the larvae by release of granule products. Eosinophils also function as antigen-presenting cells for the induction of a Th2 response. B cells produce both IgM and IgG that collaborate with neutrophils to kill worms in the adaptive immune response. Vaccine studies have identified a recombinant diagnostic antigen that induced high levels of immunity to infection with S. stercoralis in mice. These studies demonstrate that there are redundancies in …
Development Of A Mouse Monoclonal Antibody Cocktail For Post-Exposure Rabies Prophylaxis In Humans., Thomas Müller, Bernhard Dietzschold, Hildegund Ertl, Anthony R Fooks, Conrad Freuling, Christine Fehlner-Gardiner, Jeannette Kliemt, Francois X Meslin, Charles E Rupprecht, Noël Tordo, Alexander I Wanderler, Marie Paule Kieny
Development Of A Mouse Monoclonal Antibody Cocktail For Post-Exposure Rabies Prophylaxis In Humans., Thomas Müller, Bernhard Dietzschold, Hildegund Ertl, Anthony R Fooks, Conrad Freuling, Christine Fehlner-Gardiner, Jeannette Kliemt, Francois X Meslin, Charles E Rupprecht, Noël Tordo, Alexander I Wanderler, Marie Paule Kieny
Department of Microbiology and Immunology Faculty Papers
As the demand for rabies post-exposure prophylaxis (PEP) treatments has increased exponentially in recent years, the limited supply of human and equine rabies immunoglobulin (HRIG and ERIG) has failed to provide the required passive immune component in PEP in countries where canine rabies is endemic. Replacement of HRIG and ERIG with a potentially cheaper and efficacious alternative biological for treatment of rabies in humans, therefore, remains a high priority. In this study, we set out to assess a mouse monoclonal antibody (MoMAb) cocktail with the ultimate goal to develop a product at the lowest possible cost that can be used …
Signaling Through Galphai2 Protein Is Required For Recruitment Of Neutrophils For Antibody-Mediated Elimination Of Larval Strongyloides Stercoralis In Mice., Udaikumar M. Padigel, Louis Stein, Kevin Redding, James J. Lee, Thomas J. Nolan, Gerhard A. Schad, Lutz Birnbaumer, David Abraham
Signaling Through Galphai2 Protein Is Required For Recruitment Of Neutrophils For Antibody-Mediated Elimination Of Larval Strongyloides Stercoralis In Mice., Udaikumar M. Padigel, Louis Stein, Kevin Redding, James J. Lee, Thomas J. Nolan, Gerhard A. Schad, Lutz Birnbaumer, David Abraham
Department of Microbiology and Immunology Faculty Papers
The heterotrimeric guanine nucleotide-binding protein Galphai2 is involved in regulation of immune responses against microbial and nonmicrobial stimuli. Galphai2-/- mice have a selectively impaired IgM response consistent with a disorder in B cell development yet have augmented T cell effector function associated with increased production of IFN-gamma and IL-4. The goal of the present study was to determine if a deficiency in the Galphai2 protein in mice would affect the protective immune response against Strongyloides stercoralis, which is IL-4-, IL-5-, and IgM-dependent. Galphai2-/- and wild-type mice were immunized and challenged with S. stercoralis larvae and analyzed for protective immune responses …