المؤلفون: Cunliffe, Robert F, Stirling, David C, Razzano, Ilaria, Murugaiah, Valarmathy, Montomoli, Emanuele, Kim, Sungwon, Wane, Madina, Horton, Helen, Caproni, Lisa J, Tregoning, John S

المساهمون: Touchlight Genetics Ltd

المصدر: Discovery Immunology ; volume 3, issue 1 ; ISSN 2754-2483

الوصف: Influenza virus represents a challenge for traditional vaccine approaches due to its seasonal changes and potential for zoonotic transmission. Nucleic acid vaccines can overcome some of these challenges, especially through the inclusion of multiple antigens to increase the breadth of response. RNA vaccines were an important part of the response to the COVID-19 pandemic, but for future outbreaks DNA vaccines may have some advantages in terms of stability and manufacturing cost that warrant continuing investigation to fully realize their potential. Here, we investigate influenza virus vaccines made using a closed linear DNA platform, Doggybone™ DNA (dbDNA), produced by a rapid and scalable cell-free method. Influenza vaccines have mostly focussed on Haemagglutinin (HA), but the inclusion of Neuraminidase (NA) may provide additional protection. Here, we explored the potential of including NA in a dbDNA vaccine, looking at DNA optimization, mechanism and breadth of protection. We showed that DNA targeting sequences (DTS) improved immune responses against HA but not NA. We explored whether NA vaccine-induced protection against influenza virus infection was cell-mediated, but depletion of CD8 and NK cells made no impact, suggesting it was antibody-mediated. This is reflected in the restriction of protection to homologous strains of influenza virus. Importantly, we saw that including both HA and NA in a single combined vaccine did not dampen the immune response to either one. Overall, we show that linear dbDNA can induce an immune response against NA, which may offer increased protection in instances of HA mismatch where NA remains more conserved.

الإتاحة: https://doi.org/10.1093/discim/kyad030Test
https://academic.oup.com/discovimmunology/article-pdf/3/1/kyad030/55562015/kyad030.pdfTest

المؤلفون: Barreira, Maria, Kerridge, Claire, Jorda, Sara, Olofsson, Didrik, Neumann, Alexander, Horton, Helen, Smith-Moore, Sarah

المصدر: Gene Therapy ; volume 30, issue 1-2, page 122-131 ; ISSN 0969-7128 1476-5462

مصطلحات موضوعية: Genetics, Molecular Biology, Molecular Medicine

الوصف: Traditional bacterial fermentation techniques used to manufacture plasmid are time-consuming, expensive, and inherently unstable. The production of sufficient GMP grade material thus imposes a major bottleneck on industrial-scale manufacturing of lentiviral vectors (LVV). Touchlight’s linear doggybone DNA (dbDNA TM ) is an enzymatically amplified DNA vector produced with exceptional speed through an in vitro dual enzyme process, enabling industrial-scale manufacturing of GMP material in a fraction of the time required for plasmid. We have previously shown that dbDNA TM can be used to produce functional LVV; however, obtaining high LVV titres remained a challenge. Here, we aimed to demonstrate that dbDNA TM could be optimised for the manufacture of high titre LVV. We found that dbDNA TM displayed a unique transfection and expression profile in the context of LVV production, which necessitated the optimisation of DNA input and construct ratios. Furthermore, we demonstrate that efficient 3’ end processing of viral genomic RNA (vgRNA) derived from linear dbDNA TM transfer vectors required the addition of a strong 3’ termination signal and downstream spacer sequence to enable efficient vgRNA packaging. Using these improved vector architectures along with optimised transfection conditions, we were able to produce a CAR19h28z LVV with equivalent infectious titres as achieved using plasmid, demonstrating that dbDNA TM technology can provide a highly effective solution to the plasmid bottleneck.

الإتاحة: https://doi.org/10.1038/s41434-022-00343-4Test
https://www.nature.com/articles/s41434-022-00343-4.pdfTest
https://www.nature.com/articles/s41434-022-00343-4Test

المؤلفون: Wu, Xia, Roberto, Jessica B., Knupp, Allison, Greninger, Alexander L., Truong, Camtu D., Hollingshead, Nicole, Kenerson, Heidi L., Tuefferd, Marianne, Chen, Antony, Koelle, David M., Horton, Helen, Jerome, Keith R., Polyak, Stephen J., Yeung, Raymond S., Crispe, Ian N.

المساهمون: National Institute of Allergy and Infectious Diseases, U.S. Department of Defense, Janssen Research and Development, Seattle Foundation

المصدر: Frontiers in Immunology ; volume 13 ; ISSN 1664-3224

مصطلحات موضوعية: Immunology, Immunology and Allergy

الوصف: Precision-cut human liver slice cultures (PCLS) have become an important alternative immunological platform in preclinical testing. To further evaluate the capacity of PCLS, we investigated the innate immune response to TLR3 agonist (poly-I:C) and TLR4 agonist (LPS) using normal and diseased liver tissue. Pathological liver tissue was obtained from patients with active chronic HCV infection, and patients with former chronic HCV infection cured by recent Direct-Acting Antiviral (DAA) drug therapy. We found that hepatic innate immunity in response to TLR3 and TLR4 agonists was not suppressed but enhanced in the HCV-infected tissue, compared with the healthy controls. Furthermore, despite recent HCV elimination, DAA-cured liver tissue manifested ongoing abnormalities in liver immunity: sustained abnormal immune gene expression in DAA-cured samples was identified in direct ex vivo measurements and in TLR3 and TLR4 stimulation assays. Genes that were up-regulated in chronic HCV-infected liver tissue were mostly characteristic of the non-parenchymal cell compartment. These results demonstrated the utility of PCLS in studying both liver pathology and innate immunity.

الإتاحة: https://doi.org/10.3389/fimmu.2022.811551Test

المؤلفون: Horton, Helen

مصطلحات موضوعية: 572, Biological catalysts

الإتاحة: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239764Test

المؤلفون: Wu, Xia, Hollingshead, Nicole, Roberto, Jessica, Knupp, Allison, Kenerson, Heidi, Chen, Antony, Strickland, Ian, Horton, Helen, Yeung, Raymond, Soysa, Radika, Crispe, Ian N.

المساهمون: Janssen Research and Development

المصدر: Frontiers in Immunology ; volume 11 ; ISSN 1664-3224

مصطلحات موضوعية: Immunology, Immunology and Allergy

الإتاحة: https://doi.org/10.3389/fimmu.2020.02108Test

المؤلفون: Lindholm, Christina, Styche, Tim J, Horton, Helen E

المصدر: Journal of Wound Care. 30(7):534-542

مصطلحات موضوعية: Chronic, Dressing change, Dressings, Hard-to-heal, Healing, Incidence, Infection, Patient outcomes, Prevalence, Survey, Time-to-heal, Wound, Wound management

الوصف: Objective: The prevalence and economic burden of wounds are growing. Any wound has the potential to become hard-to-heal and require frequent care. Clinicians need to find ways to absorb demand on services without compromising outcomes. Drivers of wound care efficiency-time-to-heal, frequency of dressing change and the incidence of complications-can be evaluated to shape future wound management. A survey of wound care was conducted by clinicians from five centres in Sweden over a one-week period, during which clinicians documented every wound once. At the time of surveying, 49% of wounds were considered to be improving, infection incidence was 11.7% and dressings were changed a mean of 2.2 times per week, with highly exuding wounds changed 6.9 times per week. The data highlighted the importance of diagnosing patient and wound characteristics in selecting treatments and organising care. Recognised gaps in diagnoses potentially identify opportunities to influence healing, complication incidence and intensity of nursing, thus reducing demand on resources. In conclusion, this survey highlights opportunities to reduce the burdens these drivers present. Through improved diagnosis and alignment to recognised care pathways, there is potential to improve patient outcomes and alleviate the strains placed upon wound care providers.

وصف الملف: print

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:shh:diva-4173Test

المؤلفون: Janes, Holly, Friedrich, David P., Krambrink, Amy, Smith, Rebecca J., Kallas, Esper G., Horton, Helen, Casimiro, Danilo R., Carrington, Mary, Geraghty, Daniel E., Gilbert, Peter B., McElrath, M. Juliana, Frahm, Nicole

المصدر: The Journal of Infectious Diseases, 2013 Oct . 208(8), 1231-1239.

الوصول الحر: http://dx.doi.org/10.1093/infdis/jit322Test

المؤلفون: Storey, Helen L., Singa, Benson, Naulikha, Jackie, Horton, Helen, Richardson, Barbra A., John-Stewart, Grace, Walson, Judd L.

المصدر: Parasite Epidemiology and Control ; volume 2, issue 1, page 13-20 ; ISSN 2405-6731

مصطلحات موضوعية: Infectious Diseases, Parasitology, Epidemiology

الإتاحة: https://doi.org/10.1016/j.parepi.2016.12.003Test
https://api.elsevier.com/content/article/PII:S240567311630037X?httpAccept=text/plainTest
https://api.elsevier.com/content/article/PII:S240567311630037X?httpAccept=text/xmlTest

المؤلفون: Horton, Helen, Russell, Nina, Moore, Erin, Frank, Ian, Baydo, Ruth, Havenar-Daughton, Colin, Lee, Deborah, Deers, Mark, Hudgens, Michael, Weinhold, Kent, McElrath, M. Juliana

المصدر: The Journal of Infectious Diseases, 2004 Nov 01. 190(9), 1692-1696.

الوصول الحر: https://www.jstor.org/stable/30077910Test

المؤلفون: Kidzeru, Elvis, Gasper, Melanie A, Shao, Danica, Edlefsen, Paul T, Lejarcegui, Nicholas, Havyarimana, Enock, Urdahl, Kevin, Gantt, Soren, Horton, Helen, Jaspan, Heather, Gervassi, Ana

المصدر: Journal of Leukocyte Biology ; volume 110, issue 5, page 939-950 ; ISSN 0741-5400 1938-3673

مصطلحات موضوعية: Cell Biology, Immunology, Immunology and Allergy

الوصف: The role of Myeloid-Derived Suppressor Cells (MDSC) in infant immune ontogeny is unknown. Here, we evaluated MDSC frequency and relationship with infant vaccine responses throughout the first year of life in a prospective cohort study. Ninety-one South African infant-mother pairs were enrolled at delivery, and blood samples were collected at 0, 6, 10, and 14 weeks, 6 months, 9 months, and 1 year. MDSC frequencies were quantified, and immune responses to the childhood vaccines Bacillus Calmette-Guérin (BCG), hepatitis B (HepB), and combination diphtheria, tetanus, and pertussis (dTaP) were measured by Ag-specific CD4+ T cell proliferation and interferon gamma (IFN-γ) production. Vaccine-specific Ab responses to HepB, dTaP, and Haemophilus influenzae type b (Hib) were quantified via Enzyme-Linked Immunosorbent assay (ELISA). MDSC frequency in mother-infant pairs was strongly correlated; the frequency of MDSC decreased in both mothers and infants during the months after delivery/birth; and by 1 year, infant MDSC frequencies rebounded to birth levels. Higher MDSC frequency at vaccination was associated with a lack of subsequent IFN-γ release in response to vaccine Ags, with the exception of BCG. With the exception of a weak, positive correlation between MDSC frequency at 6 weeks (time of initial vaccination) and peak Hepatitis B surface antigen Ab titer, Polymorphonuclear Myeloid-Derived Suppressor Cells (PMN-MDSC) was not correlated with T cell proliferation or Ab responses in this study. The potential for MDSC-mediated suppression of vaccine Ag-specific IFN-γ responses should be explored further, and considered when evaluating candidate infant vaccines.

الإتاحة: https://doi.org/10.1002/jlb.5a0420-281rTest
https://academic.oup.com/jleukbio/article-pdf/110/5/939/49464579/jlb10875.pdfTest