scholarly journals Delineating Surface Epitopes of Lyme Disease Pathogen Targeted by Highly Protective Antibodies of New Zealand White Rabbits

2019 ◽  
Vol 87 (8) ◽  
Author(s):  
Artem S. Rogovskyy ◽  
Salvador Eugenio C. Caoili ◽  
Yurij Ionov ◽  
Helen Piontkivska ◽  
Pavel Skums ◽  
...  
Keyword(s):  
New Zealand ◽  
Lyme Disease ◽  
Protective Efficacy ◽  
Empirical Studies ◽  
Surface Expression ◽  
The United States ◽  
Mammalian Host ◽  
Content Type ◽  
Random Peptide ◽  
New Zealand White Rabbits

ABSTRACTLyme disease (LD), the most prevalent vector-borne illness in the United States and Europe, is caused byBorreliella burgdorferi. No vaccine is available for humans. Dogmatically,B. burgdorferican establish a persistent infection in the mammalian host (e.g., mice) due to a surface antigen, VlsE. This antigenically variable protein allows the spirochete to continually evade borreliacidal antibodies. However, our recent study has shown that theB. burgdorferispirochete is effectively cleared by anti-B. burgdorferiantibodies of New Zealand White rabbits, despite the surface expression of VlsE. Besides homologous protection, the rabbit antibodies also cross-protect against heterologousB. burgdorferispirochetes and significantly reduce the pathology of LD arthritis in persistently infected mice. Thus, this finding that NZW rabbits develop a unique repertoire of very potent antibodies targeting the protective surface epitopes, despite abundant VlsE, prompted us to identify the specificities of the protective rabbit antibodies and their respective targets. By applying subtractive reverse vaccinology, which involved the use of random peptide phage display libraries coupled with next-generation sequencing and our computational algorithms, repertoires of nonprotective (early) and protective (late) rabbit antibodies were identified and directly compared. Consequently, putative surface epitopes that are unique to the protective rabbit sera were mapped. Importantly, the relevance of newly identified protection-associated epitopes for their surface exposure has been strongly supported by prior empirical studies. This study is significant because it now allows us to systematically test the putative epitopes for their protective efficacy with an ultimate goal of selecting the most efficacious targets for development of a long-awaited LD vaccine.

scholarly journals New Zealand White Rabbits Effectively ClearBorrelia burgdorferiB31 despite the Bacterium’s FunctionalvlsEAntigenic Variation System

2019 ◽  
Vol 87 (7) ◽  
Author(s):  
Maliha Batool ◽  
Andrew E. Hillhouse ◽  
Yurij Ionov ◽  
Kelli J. Kochan ◽  
Fatemeh Mohebbi ◽  
...  
Keyword(s):  
New Zealand ◽  
Persistent Infection ◽  
Antigenic Variation ◽  
Surface Expression ◽  
The United States ◽  
Antimicrobial Treatment ◽  
Current Data ◽  
Content Type ◽  
Highly Evolved

ABSTRACTBorrelia burgdorferiis a tick-borne bacterium responsible for approximately 300,000 annual cases of Lyme disease (LD) in the United States, with increasing incidences in other parts of the world. The debilitating nature of LD is mainly attributed to the ability ofB. burgdorferito persist in patients for many years despite strong anti-Borreliaantibody responses. Antimicrobial treatment of persistent infection is challenging. Similar to infection of humans,B. burgdorferiestablishes long-term infection in various experimental animal models except for New Zealand White (NZW) rabbits, which clear the spirochete within 4 to 12 weeks. LD spirochetes have a highly evolved antigenic variationvlssystem, on the lp28-1 plasmid, where gene conversion results in surface expression of the antigenically variable VlsE protein. VlsE is required forB. burgdorferito establish persistent infection by continually evading otherwise potent antibodies. Since the clearance ofB. burgdorferiis mediated by humoral immunity in NZW rabbits, the previously reported results that LD spirochetes lose lp28-1 during rabbit infection could potentially explain the failure ofB. burgdorferito persist. However, the present study unequivocally disproves that previous finding by demonstrating that LD spirochetes retain thevlssystem. However, despite thevlssystem being fully functional, the spirochete fails to evade anti-Borreliaantibodies of NZW rabbits. In addition to being protective against homologous and heterologous challenges, the rabbit antibodies significantly ameliorate LD-induced arthritis in persistently infected mice. Overall, the current data indicate that NZW rabbits develop a protective antibody repertoire, whose specificities, once defined, will identify potential candidates for a much-anticipated LD vaccine.

scholarly journals Antibody Response to Lyme Disease Spirochetes in the Context of VlsE-Mediated Immune Evasion

2016 ◽  
Vol 85 (1) ◽  
Author(s):  
Artem S. Rogovskyy ◽  
David C. Gillis ◽  
Yurij Ionov ◽  
Ekaterina Gerasimov ◽  
Alex Zelikovsky
Keyword(s):  
Immune Response ◽  
Lyme Disease ◽  
Antibody Response ◽  
Antigenic Variation ◽  
Protective Efficacy ◽  
Surface Antigens ◽  
Mammalian Host ◽  
Term Survival ◽  
Content Type ◽  
Variable Surface

ABSTRACTLyme disease (LD), the most prevalent tick-borne illness in North America, is caused byBorrelia burgdorferi. The long-term survival ofB. burgdorferispirochetes in the mammalian host is achieved though VlsE-mediated antigenic variation. It is mathematically predicted that a highly variable surface antigen prolongs bacterial infection sufficiently to exhaust the immune response directed toward invariant surface antigens. If the prediction is correct, it is expected that the antibody response toB. burgdorferiinvariant antigens will become nonprotective asB. burgdorferiinfection progresses. To test this assumption, changes in the protective efficacy of the immune response toB. burgdorferisurface antigens were monitored via a superinfection model over the course of 70 days.B. burgdorferi-infected mice were subjected to secondary challenge by heterologousB. burgdorferiat different time points postinfection (p.i.). When the infected mice were superinfected with a VlsE-deficient clone (ΔVlsE) at day 28 p.i., the active anti-B. burgdorferiimmune response did not prevent ΔVlsE-induced spirochetemia. In contrast, most mice blocked culture-detectable spirochetemia induced by wild-typeB. burgdorferi(WT), indicating that VlsE was likely the primary target of the antibody response. As theB. burgdorferiinfection further progressed, however, reversed outcomes were observed. At day 70 p.i. the host immune response to non-VlsE antigens became sufficiently potent to clear spirochetemia induced by ΔVlsE and yet failed to prevent WT-induced spirochetemia. To test if any significant changes in the anti-B. burgdorferiantibody repertoire accounted for the observed outcomes, global profiles of antibody specificities were determined. However, comparison of mimotopes revealed no major difference between day 28 and day 70 antibody repertoires.

Japan joining Five Eyes would mean tough compromises

2021 ◽  
Keyword(s):  
United States ◽  
New Zealand ◽  
Prime Minister ◽  
Policy Issue ◽  
The United States ◽  
Institutional Arrangements ◽  
Potential Contribution ◽  
Content Type ◽  
Foreign Policy Issue ◽  
Opening Up

Significance The possibility of Japan joining the alliance is now seriously discussed in Tokyo and the capitals of the Five Eyes members -- the United States, United Kingdom, Canada, Australia and New Zealand. Joining Five Eyes would signal Japan’s even deeper integration into US alliance structures, regionally and globally, and raise expectations for Japan to act as a fuller ally in all sorts of contingencies. Impacts Japan’s greatest potential contribution to allies is probably in signals and imagery intelligence, especially vis-a-vis China. The prime minister will avoid opening up a controversial foreign policy issue so close to a general election; his successor may be bolder. Japan’s partners still run a risk of leaks due to Japan’s lag in cybersecurity and institutional arrangements, but this is decreasing.

scholarly journals Evaluation of RevA, a Fibronectin-Binding Protein of Borrelia burgdorferi, as a Potential Vaccine Candidate for Lyme Disease

2013 ◽  
Vol 20 (6) ◽  
pp. 892-899 ◽  
Author(s):  
Angela M. Floden ◽  
Tammy Gonzalez ◽  
Robert A. Gaultney ◽  
Catherine A. Brissette
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Passive Immunization ◽  
Surface Protein ◽  
Surface Expression ◽  
Content Type ◽  
Good Target ◽  
Potential Vaccine ◽  
Mammalian Infection

ABSTRACTPrevious studies indicated that the Lyme disease spirocheteBorrelia burgdorferiexpresses the RevA outer surface protein during mammalian infection. As an adhesin that promotes bacterial interaction with fibronectin, RevA appears to be a good target for preventive therapies. RevA proteins are highly conserved across all Lyme borreliae, and antibodies against RevA protein are cross-reactive among RevA proteins from diverse strains. Mice infected withB. burgdorferimounted a rapid IgM response to RevA, followed by a strong IgG response that generally remained elevated for more than 12 months, suggesting continued exposure of RevA protein to the immune system. RevA antibodies were bactericidalin vitro. To evaluate the RevA antigen as a potential vaccine, mice were vaccinated with recombinant RevA and challenged withB. burgdorferiby inoculation with a needle or by a tick bite. Cultured tissues from all treatment groups were positive forB. burgdorferi. Vaccinated animals also appeared to have similar levels ofB. burgdorferiDNA compared to nonvaccinated controls. Despite its antigenicity, surface expression, and the production of bactericidal antibodies against it, RevA does not protect againstBorrelia burgdorferiinfection in a mouse model. However, passive immunization with anti-RevA antibodies did prevent infection, suggesting the possible utility of RevA-based immunotherapeutics or vaccine.

Divergence on Chinese 5G strains 'Five Eyes' alliance

2019 ◽  
Keyword(s):  
United States ◽  
United Kingdom ◽  
New Zealand ◽  
Market Share ◽  
The United States ◽  
Content Type ◽  
The United Kingdom ◽  
Intelligence Sharing ◽  
The Stability ◽  
The Eu

Subject Outlook for the Five Eyes alliance. Significance The stability of the Five Eyes intelligence sharing partnership between Australia, Canada, New Zealand, the United Kingdom and the United States is under stress over Chinese participation in the members’ 5G telecommunications networks. Impacts Possible US concessions on the supply chains of Chinese firms would ease strain within the Five Eyes alliance. European corporates will redouble efforts to burnish their security credentials to capture 5G market share. London’s eventual decision on Huawei will influence the EU and Asian democracies.

Mining supply disruptions mask mounting demand fears

2020 ◽  
Keyword(s):  
United States ◽  
South Africa ◽  
New Zealand ◽  
Iron Ore ◽  
The United States ◽  
Middle Ground ◽  
Content Type ◽  
Supply Disruptions ◽  
Copper Mines ◽  
Southern Neighbour

Subject COVID-19-related disruptions to the mining supply chain. Significance The severity and length of COVID-19-related lockdowns has varied by country, but disruptions have quickly affected production. While West Africa, Russia and initially Mexico struggled to define a clear policy for mining, strict initial prohibition hit production in New Zealand, Peru, Argentina, South Africa, Ecuador and India in late March and into April. Spain, Australia, Chile, Quebec and Finland stuck to the middle ground, phasing policies in and out and permitting selected activity. Impacts Key plants, including iron ore mines in Australia and copper mines in Chile and the United States, are seeing little disruption so far. Mongolia, the first nation to close its borders with China, has also been the first to resume coal exports to its southern neighbour. Western Australia banned some fly-in, fly-out commuting arrangements to mines; similar such bans could persist elsewhere for months.

scholarly journals Antibodies to Borrelia burgdorferi OspA, OspC, OspF, and C6 Antigens as Markers for Early and Late Infection in Dogs

2012 ◽  
Vol 19 (4) ◽  
pp. 527-535 ◽  
Author(s):  
Bettina Wagner ◽  
Heather Freer ◽  
Alicia Rollins ◽  
David Garcia-Tapia ◽  
Hollis N. Erb ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
The United States ◽  
Sensu Stricto ◽  
Antibody Responses ◽  
Surface Proteins ◽  
Early Infection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Content Type ◽  
Antibody Levels

ABSTRACTLyme disease in the United States is caused byBorrelia burgdorferisensu stricto, which is transmitted to mammals by infected ticks.Borreliaspirochetes differentially express immunogenic outer surface proteins (Osp). Our aim was to evaluate antibody responses to Osp antigens to aid the diagnosis of early infection and the management of Lyme disease. We analyzed antibody responses during the first 3 months after the experimental infection of dogs using a novel multiplex assay. Results were compared to those obtained with two commercial assays detecting C6 antigen. Multiplex analysis identified antibodies to OspC and C6 as early as 3 weeks postinfection (p.i.) and those to OspF by 5 weeks p.i. Antibodies to C6 and OspF increased throughout the study, while antibodies to OspC peaked between 7 and 11 weeks p.i. and declined thereafter. A short-term antibody response to OspA was observed in 3/8 experimentally infected dogs on day 21 p.i. Quant C6 enzyme-linked immunosorbent assay (ELISA) results matched multiplex results during the first 7 weeks p.i.; however, antibody levels subsequently declined by up to 29%. Immune responses then were analyzed in sera from 125 client-owned dogs and revealed high agreement between antibodies to OspF and C6 as robust markers for infection. Results from canine patient sera supported that OspC is an early infection marker and antibodies to OspC decline over time. The onset and decline of antibody responses toB. burgdorferiOsp antigens and C6 reflect their differential expression during infection. They provide valuable tools to determine the stage of infection, treatment outcomes, and vaccination status in dogs.

scholarly journals The Borrelia burgdorferi Glycosaminoglycan Binding Protein Bgp in the B31 Strain Is Not Essential for Infectivity despite Facilitating Adherence and Tissue Colonization

2017 ◽  
Vol 86 (2) ◽  
Author(s):  
Samantha Schlachter ◽  
Janakiram Seshu ◽  
Tao Lin ◽  
Steven Norris ◽  
Nikhat Parveen
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Binding Protein ◽  
Mammalian Host ◽  
Infection Model ◽  
Binding Assays ◽  
Content Type ◽  
Mouse Infection Model ◽  
Successful Infection

ABSTRACTThe Lyme disease-causing organismBorrelia burgdorferiis transmitted into the mammalian host by an infected-tick bite. Successful infection relies on the ability of this extracellular pathogen to persist and colonize different tissues.B. burgdorferiencodes a large number of adhesins that are able to interact with host ligands to facilitate adherence and tissue colonization. Multiple glycosaminoglycan binding proteins present inB. burgdorferioffer a degree of redundancy of function during infection, and this highlights the importance of glycosaminoglycans as host cell receptors for spirochete adherence. Of particular interest in this study isBorreliaglycosaminoglycan binding protein (Bgp), which binds to heparin-related glycosaminoglycans. The properties of abgptransposon mutant and atrans-complemented derivative were compared to those of the wild-typeB. burgdorferiin thein vitrobinding assays and in infection studies using a C3H/HeJ mouse infection model. We determined that the loss of Bgp impairs spirochete adherence, infectivity, and tissue colonization, resulting in a reduction of inflammatory manifestations of Lyme disease. Although Bgp is not essential for infectivity, it is an important virulence factor ofB. burgdorferithat allows adherence and tissue colonization and contributes to disease severity.

Exploring Indigenous education leadership research in Canada, the United States, Australia and New Zealand

2020 ◽  
Vol 22 (4) ◽  
pp. 281-297
Author(s):  
Xiao Fan ◽  
Peng Liu
Keyword(s):  
New Zealand ◽  
Educational Leadership ◽  
Indigenous Education ◽  
Education Leadership ◽  
The United States ◽  
Counting Method ◽  
Content Type ◽  
English Speaking ◽  
Leadership Research ◽  
Vote Counting

PurposeThis literature systematically reviews articles published in “core” international journals on the topic of Indigenous education leadership over the period from 2000 to 2018 in four English-speaking countries, covering Canada, America, Australia and New Zealand, in which all of them have long colonial history and Indigenous population. These reviews provide insights into the nature of this emergent literature and generate many implications that required for further research in Indigenous education leadership.Design/methodology/approachIn this study, a vote counting method was employed and a clearly delimited body of research on Indigenous education leadership was also identified. The vote counting method can enlarge the perspectives on the noticeable heterogeneity of Indigenous education leadership within the four English-speaking countries. This is the basic constitutive element for the development of a comparative literature in Indigenous education leadership. Moreover, this method can clearly calculate the annual number of articles about Indigenous education leadership, and the various methods used in the publications of Indigenous education leadership can be figured out as well, which helps to find out the different patterns of changes on Indigenous education leadership.FindingsThis study identifies the patterns of Indigenous educational leadership research across four English-speaking countries, which will contribute to the development of research in this regard.Originality/valueThis is one of the first studies about Indigenous educational leadership in the world. It will not only contribute to education practice but also leadership theory development.

China may drive multilateral digital trade framework

2021 ◽  
Keyword(s):  
United States ◽  
New Zealand ◽  
South Korea ◽  
The United States ◽  
Trade Integration ◽  
Content Type ◽  
The Eu

Significance DEPA was concluded by its founding members -- Singapore, New Zealand and Chile -- in 2020. South Korea applied to participate in June this year. Canada has expressed interest. China's accession would greatly raise its profile, but creates difficulties both for existing members and for Beijing. Impacts Other countries may take DEPA more seriously as a result of China's application. The United States and the EU may be spurred to devote greater attention to global digital trade integration. China's fundamentally sovereignty-based approach to data is unlikely to change.

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