Article
Biotechnology & Applied Microbiology
Matthew Pine, Gunjan Arora, Thomas M. Hart, Emily Bettini, Brian T. Gaudette, Hiromi Muramatsu, Istvan Tombacz, Taku Kambayashi, Ying K. Tam, Dustin Brisson, David Allman, Michela Locci, Drew Weissman, Erol Fikrig, Norbert Pardi
Summary: This study proposes the development of a Lyme disease vaccine using the mRNA-LNP platform, which induces stronger immune responses and provides protection against bacterial infection compared to traditional protein subunit vaccines.
Article
Infectious Diseases
Paulina Bierwagen, Joanna Sliwiak, Mariusz Jaskolski, Anna Urbanowicz
Summary: Ticks of the genus Ixodes are parasites that feed on vertebrate blood and act as vectors for various pathogenic microbes, including the causative agent of Lyme borreliosis. The saliva of these ticks contains bioactive molecules, with the Salp15 protein being a well-studied component that suppresses the host immune response and interacts with Borrelia burgdorferi spirochetes. Recent research has shown that in addition to Salp15, other homologues from Ixodes ricinus are also capable of binding to the outer surface protein C (OspC) of Borrelia burgdorferi, potentially aiding in evading the host immune system.
TICKS AND TICK-BORNE DISEASES
(2021)
Article
Immunology
Priyanka G. Mukherjee, Dionysios Liveris, Klara Hanincova, Radha Iyer, Gary P. Wormser, Weihua Huang, Ira Schwartz
Summary: Lyme disease in the United States is mainly caused by Borrelia burgdorferi sensu stricto. After a tick bite, patients may develop erythema migrans. If dissemination occurs, neurologic manifestations, carditis, or arthritis may follow. OspC, a surface protein, is essential in early infection, but it is not the sole determinant of dissemination.
INFECTION AND IMMUNITY
(2023)
Article
Microbiology
Tatiana N. N. Castro-Padovani, Timothy C. C. Saylor, Olivia T. T. Husted, Andrew C. C. Krusenstjerna, Nerina Jusufovic, Brian Stevenson
Summary: Borrelia burgdorferi sensu lato requires the OspC protein to infect humans and other vertebrate hosts. Bacteria that do not produce OspC or fail to downregulate OspC after infection are rapidly cleared. OspC is essential for the initial phase of vertebrate infection by Lyme disease spirochetes.
JOURNAL OF BACTERIOLOGY
(2023)
Article
Multidisciplinary Sciences
Jenny Wachter, Britney Cheff, Chad Hillman, Valentina Carracoi, David W. Dorward, Craig Martens, Kent Barbian, Glenn Nardone, L. Renee Olano, Margie Kinnersley, Patrick R. Secor, Patricia A. Rosa
Summary: The alternative sigma factor RpoS plays a crucial role in the critical host-adaptive response of Borrelia burgdorferi, the Lyme disease spirochete. This study characterises the negative regulator bbd18 of RpoS and demonstrates its essential nature for the viability of wild-type spirochetes in vitro and in vivo. Transcriptomic analyses reveal that BBD18 depletion leads to global induction of RpoS-dependent genes, which can be circumvented by deletion of rpoS.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Michelle J. Klouwens, Jos J. A. Trentelman, Alex Wagemakers, Jasmin Ersoz, Adriaan D. Bins, Joppe W. Hovius
Summary: DNA tattoo vaccination with OspC induced high specific IgG titers and provided near-total protection against B. burgdorferi ss infection by tick challenge. In contrast, DNA tattoo vaccines against tick proteins TSLPI, Salp15, tHRF, and Tix-5 induced low to moderate IgG titers and did not provide protection. Therefore, DNA tattoo vaccination is not a suitable strategy to identify or screen tick antigens for anti-tick vaccines, but it is an effective platform to assess novel B. burgdorferi sl antigen candidates in relevant tick challenge models.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biology
Foekje F. Stelma, Anneleen Berende, Hadewych Ter Hofstede, Hedwig D. Vrijmoeth, Fidel Vos, Bart-Jan Kullberg
Summary: This paper presents a study aimed at determining whether serology can differentiate between patients with persistent symptoms attributed to Lyme and other patients with Lyme borreliosis. The study results show that serological testing is unable to define the subgroup of patients with persistent symptoms attributed to Lyme borreliosis.
Article
Ecology
Lars Raberg, Dagmar Clough, Asa Hagstrom, Kristin Scherman, Martin Andersson, Anna Drews, Maria Strandh, Barbara Tschirren, Helena Westerdahl
Summary: In this study, it was found that MHC alleles (DQB*37) affect the susceptibility and resistance of bank voles to different strains of the tick-transmitted bacterium. Furthermore, the MHC alleles also influence the diversity of the infecting strains.
Article
Microbiology
Mateusz Markowicz, Michael Reiter, Jutta Gamper, Gerold Stanek, Hannes Stockinger
Summary: The study aimed to investigate the etiology of persistent IgM antibodies against Borrelia burgdorferi sensu lato (sl) and their association with nonspecific symptoms. It was found that the persistence of IgM antibodies were specific for the C-terminal PKKP motif of OspC, although cross-reactivity with other eukaryotic and/or prokaryotic antigens may affect the specificity of OspC in the serological diagnosis of Lyme borreliosis. Additionally, lack of improvement in nonspecific symptoms was associated with higher IgM ELISA values.
MICROBIOLOGY SPECTRUM
(2021)
Review
Microbiology
Brian Stevenson
Summary: The Lyme disease spirochete persists in nature through cycles between ticks and vertebrates, but it has a limited ability to sense its external environment. Detailed investigations on Borrelia burgdorferi have revealed the molecular mechanisms through which it controls production of virulence-associated factors. This has led to the development of a model explaining how B. burgdorferi controls expression of its diverse proteins through changes triggered by specific physiological and metabolic states during its infectious cycle.
CURRENT OPINION IN MICROBIOLOGY
(2023)
Article
Ecology
Lia Di, Saymon Akther, Edgaras Bezrucenkovas, Larisa Ivanova, Brian Sulkow, Bing Wu, Saad Mneimneh, Maria Gomes-Solecki, Wei-Gang Qiu
Summary: Natural populations of pathogens and their hosts are engaged in an arms race, posing challenges to vaccine and diagnostic development. Using evolutionary and centroid algorithms, synthetic antigens with promising reactivity against diverse pathogen strains have been generated. The Maximum Antigen Diversification (MAD) model offers a novel approach to combating pathogen diversity.
Article
Immunology
Fuad Alanazi, Sajith Raghunandanan, Raj Priya, X. Frank Yang
Summary: This study identified the crucial role of the Rrp2-RpoN-RpoS pathway in blood-brain barrier transmigration and invasion of the central nervous system by Borrelia burgdorferi. The major surface lipoprotein OspC was found to be a significant contributor to blood-brain barrier transmigration. Other major surface lipoproteins controlled by this pathway, DbpA/B and BBK32, were less important for blood-brain barrier transmigration. The surface lipoprotein OspA and the Rrp1 pathway, required for B. burgdorferi colonization in the tick vector, were not necessary for blood-brain barrier transmigration.
INFECTION AND IMMUNITY
(2023)
Article
Infectious Diseases
Mehrnaz Nouri, Neus Latorre-Margalef, Agnieszka Czopek, Lars Raberg
Summary: The study found that different mouse strains have varying levels of antibody cross-reactivity to different OspC types, with C3H strain showing higher levels. There was evidence for asymmetry in crossreactivity, with antibodies to OspC2 showing stronger cross-reactivity with OspC9 than vice versa, which may impact the coexistence of OspC types.
INFECTION GENETICS AND EVOLUTION
(2021)
Article
Microbiology
Sonya G. Zawada, Michael E. von Fricken, Thomas A. Weppelmann, Masoumeh Sikaroodi, Patrick M. Gillevet
Summary: Investigating the genetic types of Borreliella burgdorferi in different tissues of white-footed mice can contribute to our understanding of Lyme disease and the diverse clinical manifestations associated with infection. This study provides evidence for genetic variability in B. burgdorferi within local mouse populations and even within individual hosts by tissue type. These findings highlight the importance of expanding surveillance on the epigenetics of B. burgdorferi across reservoirs, ticks, and infected patients.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
Castillo Daniel, Jorgensen Johanna, Sundell Krister, Madsen Lone, Dalsgaard Inger, Wiklund Tom, Middelboe Mathias
Summary: This study analyzed the genetic diversity of F. psychrophilum hosts and phages from the Baltic Sea area to identify genetic determinants of phage-host interaction patterns. The host range analysis identified nine phage clusters, indicating specific genetic variations linked to variability in phage infection patterns. This highlights the importance of phages as drivers of core genomic diversity in F. psychrophilum.
ENVIRONMENTAL MICROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Ryan J. Schulze, Eugene W. Krueger, Shaun G. Weller, Katherine M. Johnson, Carol A. Casey, Micah B. Schott, Mark A. McNiven
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biochemical Research Methods
Swathi R. Pullagurla, Prashant Kumar, Oluwadara Ogun, Ozan S. Kumru, Ahd Hamidi, Femke Hoeksema, Christopher Yallop, Julie E. Bines, David B. Volkin, Sangeeta B. Joshi
Summary: This study used linear regression and Arrhenius modeling to predict the real-time stability profiles of a live-virus vaccine. The predictions were validated using high-throughput assays and control groups, and the study concluded with a ranking of the vaccine formulations.
Article
Multidisciplinary Sciences
Neil C. Dalvie, Lisa H. Tostanoski, Sergio A. Rodriguez-Aponte, Kawaljit Kaur, Sakshi Bajoria, Ozan S. Kumru, Amanda J. Martinot, Abishek Chandrashekar, Katherine McMahan, Noe B. Mercado, Jingyou Yu, Aiquan Chang, Victoria M. Giffin, Felix Nampanya, Shivani Patel, Lesley Bowman, Christopher A. Naranjo, Dongsoo Yun, Zach Flinchbaugh, Laurent Pessaint, Renita Brown, Jason Velasco, Elyse Teow, Anthony Cook, Hanne Andersen, Mark G. Lewis, Danielle L. Camp, Judith Maxwell Silverman, Gaurav S. Nagar, Harish D. Rao, Rakesh R. Lothe, Rahul Chandrasekharan, Meghraj P. Rajurkar, Umesh S. Shaligram, Harry Kleanthous, Sangeeta B. Joshi, David B. Volkin, Sumi Biswas, J. Christopher Love, Dan H. Barouch
Summary: Authorized vaccines against SARS-CoV-2 are not widely available in low- and middle-income countries due to supply shortages, high costs, and complex storage requirements. However, a new vaccine candidate using widely available, safe adjuvants has shown promising results in animal trials, eliciting protective immunity and demonstrating the potential benefits of a low-cost modular vaccine platform for SARS-CoV-2 and other variants.
Article
Chemistry, Medicinal
Kaushal Jerajani, Ying Wan, John M. Hickey, Ozan S. Kumru, Nitya Sharma, Swathi R. Pullagurla, Oluwadara Ogun, Shweta Mapari, Neal Whitaker, Sarah Brendle, Neil D. Christensen, Saurabh Batwal, Mustafa Mahedvi, Harish Rao, Vikas Dogar, Rahul Chandrasekharan, Umesh Shaligram, Sangeeta B. Joshi, David B. Volkin
Summary: Introducing multi-dose formulations of Human Papillomavirus (HPV) vaccines can reduce costs and improve vaccine coverage globally. This study focuses on the development of key analytical methods for the formulation development of HPV vaccines. The study includes the selection of appropriate physicochemical methods, the characterization of HPV vaccines, the development of stability-indicating competitive ELISA assays, and the evaluation of preservative stability and effectiveness. The results discuss the analytical challenges encountered and highlight the importance of high-throughput methods for the development of aluminum-adjuvanted protein-based vaccine candidates.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Chemistry, Medicinal
Kaushal Jerajani, Ying Wan, Ozan S. Kumru, Swathi R. Pullagurla, Prashant Kumar, Nitya Sharma, Oluwadara Ogun, Shweta Mapari, Sarah Brendle, Neil D. Christensen, Saurabh Batwal, Mustafa Mahedvi, Harish Rao, Vikas Dogar, Rahul Chandrasekharan, Umesh Shaligram, Sangeeta B. Joshi, David B. Volkin
Summary: The study evaluated the combination of different antimicrobial preservatives (APs) at lower concentrations with Human Papillomavirus (HPV) Virus-Like Particles (VLPs) to maintain both antimicrobial effectiveness and antigen stability. Screening strategies were used to identify promising AP combinations, and the selected combinations were validated through additional experiments.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Timothy C. Saylor, Timothy Casselli, Kathryn G. Lethbridge, Jessamyn P. Moore, Katie M. Owens, Catherine A. Brissette, Wolfram R. Zuckert, Brian Stevenson
Summary: Some bacteria respond to antibiotic stress by altering their transcription profiles, and this study found that Borrelia burgdorferi, the spirochetal agent of Lyme disease, exhibits genetically-encoded responses to doxycycline by increasing the production of proteins involved in translation.
Article
Microbiology
Bryan T. Murphy, Jacob J. Wiepen, Huan He, Ankita S. Pramanik, Jason M. Peters, Brian Stevenson, Wolfram R. Zueckert
Summary: In this study, a single plasmid-based, fully inducible, and nontoxic CRISPR interference (CRISPRi) system was established for transcriptional silencing of Borrelia burgdorferi genes and operons. The system effectively silenced target genes and made the study of Borrelia burgdorferi more convenient.
JOURNAL OF BACTERIOLOGY
(2023)
Article
Chemistry, Medicinal
Nitya Sharma, Kaushal Jerajani, Ying Wan, Ozan S. Kumru, Swathi R. Pullagurla, Oluwadara Ogun, Shweta Mapari, Sarah Brendle, Neil D. Christensen, Saurabh Batwal, Mustafa Mahedvi, Harish Rao, Vikas Dogar, Rahul Chandrasekharan, Umesh Shaligram, David B. Volkin, Sangeeta B. Joshi
Summary: This work outlines the development of a multi-dose formulation for a Human Papillomavirus (HPV) Virus-Like Particle (VLP) based vaccine. Storage stability studies identified eight lead candidates for the formulation, with optimal stability and antimicrobial effectiveness observed with certain preservatives.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Timothy C. Saylor, Christina R. Savage, Andrew C. Krusenstjerna, Nerina Jusufovic, Wolfram R. Zueckert, Catherine A. Brissette, Md Motaleb, Paula J. Schlax, Brian Stevenson
Summary: The Borrelia burgdorferi SpoVG protein exhibits different affinities for various RNAs, ssDNAs, and dsDNAs. Mutagenesis studies suggest that the formation of SpoVG-nucleic acid complexes is not solely dependent on sequence or structure. The substitution of uracil with thymine in ssDNAs does not affect protein-nucleic acid complex formation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Immunology
Timothy Casselli, Yvonne Tourand, Kaitlyn Gura, Brian Stevenson, Wolfram R. R. Zuckert, Catherine A. A. Brissette
Summary: This study reveals the role of endogenous plasmids in mammalian infection and restriction protection in the Lyme disease spirochete Borrelia mayonii. Infection of C3H mice with B. mayonii leads to bacterial dissemination and persistence in peripheral tissues, and loss of certain endogenous plasmids correlates with reduced infectivity in mice.
INFECTION AND IMMUNITY
(2023)
Article
Biochemistry & Molecular Biology
Huan He, Ankita S. Pramanik, Selene K. Swanson, David K. Johnson, Laurence Florens, Wolfram R. Zuckert
Summary: Borrelia spirochetes lack lipopolysaccharide (LPS) in the outer membrane (OM) and have abundant surface-exposed lipoproteins. Little is known about the translocation of these lipoproteins through the periplasm and OM. This study characterized BB0838, a protein homologous to the LPS assembly protein LptD, and found that it plays a crucial role in cell growth and envelope stability in Borrelia burgdorferi. Knockdown of BB0838 resulted in the periplasmic retention of surface lipoproteins, indicating that BB0838 is involved in their secretion. The findings suggest that BB0838/LptD(Bb) facilitates the essential step in spirochetal surface lipoprotein secretion.
MOLECULAR MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Payton A. -B. Weidenbacher, Mrinmoy Sanyal, Natalia Friedland, Shaogeng Tang, Prabhu S. Arunachalam, Mengyun Hu, Ozan S. Kumru, Mary Kate Morris, Jane Fontenot, Lisa Shirreff, Jonathan Do, Ya-Chen Cheng, Gayathri Vasudevan, Mark B. Feinberg, Francois J. Villinger, Carl Hanson, Sangeeta B. Joshi, David B. Volkin, Bali Pulendran, Peter S. Kim
Summary: While the development of COVID-19 vaccines has been successful, there is a need for a globally available vaccine that provides longer-lasting immunity against current and future variants of concern. One potential vaccine candidate is DCFHP, a protein-nanoparticle vaccine formulated with aluminum hydroxide as the adjuvant. It has shown promising results in eliciting potent and durable neutralizing antibodies in non-human primates against known variants and can be produced in large quantities. DCFHP has the potential to be used as a booster vaccine or as a primary vaccine for pediatric use.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Sakshi Bajoria, Lorena R. Antunez, Ozan S. Kumru, Mark Klempner, Yang Wang, Lisa A. Cavacini, Sangeeta B. Joshi, David B. Volkin
Summary: This study investigates the feasibility of low-cost, oral passive immunization using secretory IgA antibodies (sIgA) against enterotoxigenic Escherichia coli (ETEC). Different formulations were evaluated for stability during storage and in in vitro digestion models. The results demonstrate the potential of single-vial, liquid formulations of sIgA antibodies for passive immunization after infant feeding.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Immunology
Ozan S. Kumru, Mrinmoy Sanyal, Natalia Friedland, John M. Hickey, Richa Joshi, Payton Weidenbacher, Jonathan Do, Ya-Chen Cheng, Peter S. Kim, Sangeeta B. Joshi, David B. Volkin
Summary: This study investigated the formulation and comparability of a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen with an aluminum-salt adjuvant. The adjuvanted formulation showed enhanced pseudovirus neutralization titers and differed in their in vitro stability properties. The DCFHP antigen produced in two different cell lines displayed expected differences in glycoforms but showed similar key quality attributes. These findings support the future development of an AH-adjuvanted DCFHP vaccine candidate.
Correction
Multidisciplinary Sciences
Payton A. -B. Weidenbacher, Mrinmoy Sanyal, Natalia Friedland, Shaogeng Tang, Prabhu S. Arunachalam, Mengyun Hu, Ozan S. Kumru, Mary Kate Morris, Jane Fontenot, Lisa Shirreff, Jonathan Do, Ya-Chen Cheng, Gayathri Vasudevan, Mark B. Feinberg, Francois J. Villinger, Carl Hanson, Sangeeta B. Joshi, David B. Volkin, Bali Pulendran, Peter S. Kim
NATURE COMMUNICATIONS
(2023)