Publications by authors named "M J Forner"

62 Publications

Peptide-Based Vaccines: Foot-and-Mouth Disease Virus, a Paradigm in Animal Health.

Vaccines (Basel) 2021 May 8;9(5). Epub 2021 May 8.

Departament de Ciències Experimentals i de la Salut (DCEXS-UPF), 08003 Barcelona, Spain.

Vaccines are considered one of the greatest global health achievements, improving the welfare of society by saving lives and substantially reducing the burden of infectious diseases. However, few vaccines are fully effective, for reasons ranging from intrinsic limitations to more contingent shortcomings related, e.g., to cold chain transport, handling and storage. In this context, subunit vaccines where the essential antigenic traits (but not the entire pathogen) are presented in rationally designed fashion have emerged as an attractive alternative to conventional ones. In particular, this includes the option of fully synthetic peptide vaccines able to mimic well-defined B- and T-cell epitopes from the infectious agent and to induce protection against it. Although, in general, linear peptides have been associated to low immunogenicity and partial protection, there are several strategies to address such issues. In this review, we report the progress towards the development of peptide-based vaccines against foot-and-mouth disease (FMD) a highly transmissible, economically devastating animal disease. Starting from preliminary experiments using single linear B-cell epitopes, recent research has led to more complex and successful second-generation vaccines featuring peptide dendrimers containing multiple copies of B- and T-cell epitopes against FMD virus or classical swine fever virus (CSFV). The usefulness of this strategy to prevent other animal and human diseases is discussed.
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http://dx.doi.org/10.3390/vaccines9050477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150788PMC
May 2021

Ten-year assessment of a cancer fast-track programme to connect primary care with oncology: reducing time from initial symptoms to diagnosis and treatment initiation.

ESMO Open 2021 Jun 11;6(3):100148. Epub 2021 May 11.

Department of Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain. Electronic address:

Background: Cancer is the second leading cause of mortality worldwide. Integrating different levels of care by implementing screening programmes, extending diagnostic tools and applying therapeutic advances may increase survival. We implemented a cancer fast-track programme (CFP) to shorten the time between suspected cancer symptoms, diagnosis and therapy initiation.

Patients And Methods: Descriptive data were collected from the 10 years since the CFP was implemented (2009-2019) at the Clinico-Malvarrosa Health Department in Valencia, Spain. General practitioners (GPs), an oncology coordinator and 11 specialists designed guidelines for GP patient referral to the CFP, including criteria for breast, digestive, gynaecological, lung, urological, dermatological, head and neck, and soft tissue cancers. Patients with enlarged lymph nodes and constitutional symptoms were also considered. On identifying patients with suspected cancer, GPs sent a case proposal to the oncology coordinator. If criteria were met, an appointment was quickly made with the patient. We analysed the timeline of each stage of the process.

Results: A total of 4493 suspected cancer cases were submitted to the CFP, of whom 4019 were seen by the corresponding specialist. Cancer was confirmed in 1098 (27.3%) patients: breast cancer in 33%, urological cancers in 22%, gastrointestinal cancer in 19% and lung cancer in 15%. The median time from submission to cancer testing was 11 days, and diagnosis was reached in a median of 19 days. Treatment was started at a median of 34 days from diagnosis.

Conclusions: The findings of this study show that the interval from GP patient referral to specialist testing, cancer diagnosis and start of therapy can be reduced. Implementation of the CFP enabled most patients to begin curative intended treatment, and required only minimal resources in our setting.
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http://dx.doi.org/10.1016/j.esmoop.2021.100148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136438PMC
June 2021

IgA-Dominant Infection-Associated Glomerulonephritis Following SARS-CoV-2 Infection.

Viruses 2021 03 31;13(4). Epub 2021 Mar 31.

Nephrology Department, Hospital Clínico Universitario, INCLIVA, Universidad de Valencia, 46010 Valencia, Spain.

The renal involvement of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported. The etiology of kidney injury appears to be tubular, mainly due to the expression of angiotensin-converting enzyme 2, the key joint receptor for SARS-CoV-2; however, cases with glomerular implication have also been documented. The multifactorial origin of this renal involvement could include virus-mediated injury, cytokine storm, angiotensin II pathway activation, complement dysregulation, hyper-coagulation, and microangiopathy. We present the renal histological findings from a patient who developed acute kidney injury and de novo nephrotic syndrome, highly suggestive of acute IgA-dominant infection-associated glomerulonephritis (IgA-DIAGN) after SARS-CoV-2 infection, as evidenced by the presence of this virus detected in the renal tissue of the patient via immunohistochemistry assay. In summary, we document the first case of IgA-DIAGN associated to SARS-CoV-2. Thus, SARS-CoV-2 S may act as a super antigen driving the development of multisystem inflammatory syndrome as well as cytokine storm in patients affected by COVID-19, reaching the glomerulus and leading to the development of this novel IgA-DIAGN.
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http://dx.doi.org/10.3390/v13040587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066364PMC
March 2021

An Efficient Agrobacterium-Mediated Transformation Protocol for Hexaploid and Tetraploid Wheat.

Curr Protoc 2021 Mar;1(3):e58

John Innes Centre, Department of Crop Genetics, Norwich Research Park, Norwich, Norfolk, UK.

Wheat, though a key crop plant with considerable influence on world food security, has nonetheless trailed behind other major cereals in the advancement of gene transformation technology for its improvement. New breeding technologies such as genome editing allow precise DNA manipulation, but their potential is limited by low regeneration efficiencies in tissue culture and the lack of transformable genotypes. We developed, in the hexaploid spring wheat cultivar "Fielder," a robust, reproducible Agrobacterium tumefaciens-mediated transformation system with transformation efficiencies of up to 33%. The system requires immature embryos as starting material and includes a centrifugation pretreatment before the inoculation with Agrobacterium. This high-throughput, highly efficient, and repeatable transformation system has been used effectively to introduce genes of interest for overexpression, RNA interference, and CRISPR-Cas-based genome editing. With slight modifications reported here, the standard protocol can be applied to the hexaploid wheat "Cadenza" and the tetraploid durum wheat "Kronos" with efficiencies of up to 4% and 10%, respectively. The system has also been employed to assess the developmental gene fusion GRF-GIF with outstanding results. In our hands, this technology combined with our transformation system improved transformation efficiency to 77.5% in Fielder. This combination should help alleviate the genotype dependence of wheat transformation, allowing new genome-editing tools to be used directly in more elite wheat varieties. © 2021 The Authors. Basic Protocol 1: Growing of donor plants Basic Protocol 2: Transformation of Agrobacterium with vector by electroporation Basic Protocol 3: Starting material collection, sterilization, and embryo inoculation Basic Protocol 4: Selection, regeneration, rooting, and acclimatization of transformants.
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http://dx.doi.org/10.1002/cpz1.58DOI Listing
March 2021

Swine T-Cells and Specific Antibodies Evoked by Peptide Dendrimers Displaying Different FMDV T-Cell Epitopes.

Front Immunol 2020 3;11:621537. Epub 2021 Feb 3.

Microbes in Health and Welfare Unit, Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Madrid, Spain.

Dendrimeric peptide constructs based on a lysine core that comprises both B- and T-cell epitopes of foot-and-mouth disease virus (FMDV) have proven a successful strategy for the development of FMD vaccines. Specifically, BT dendrimers displaying two copies of the major type O FMDV antigenic B-cell epitope located on the virus capsid [VP1 (140-158)], covalently linked to a heterotypic T-cell epitope from either non-structural protein 3A [3A (21-35)] or 3D [3D (56-70)], named BT-3A and BT-3D, respectively, elicit high levels of neutralizing antibodies (nAbs) and IFN-γ-producing cells in pigs. To assess whether the inclusion and orientation of T-3A and T-3D T-cell epitopes in a single molecule could modulate immunogenicity, dendrimers with T epitopes juxtaposed in both possible orientations, i.e., constructs BTT-3A3D and BTT-3D3A, were made and tested in pigs. Both dendrimers elicited high nAbs titers that broadly neutralized type O FMDVs, although BTT-3D3A did not respond to boosting, and induced lower IgGs titers, in particular IgG2, than BTT-3A3D. Pigs immunized with B a control dendrimer displaying two B-cell epitope copies and no T-cell epitope, gave no nABs, confirming T-3A and T-3D as T helper epitopes. The T-3D peptide was found to be an immunodominant, as it produced more IFN-γ expressing cells than T-3A in the recall assay. Besides, in pigs immunized with the different dendrimeric peptides, CD4 T-cells were the major subset contributing to IFN-γ expression upon recall, and depletion of CD4 cells from PBMCs abolished the production of this cytokine. Most CD4IFN-γ cells showed a memory (CD42E3) and a multifunctional phenotype, as they expressed both IFN-γ and TNF-α, suggesting that the peptides induced a potent Th1 pro-inflammatory response. Furthermore, not only the presence, but also the orientation of T-cell epitopes influenced the T-cell response, as BTT-3D3A and B groups had fewer cells expressing both cytokines. These results help understand how BT-type dendrimers triggers T-cell populations, highlighting their potential as next-generation FMD vaccines.
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http://dx.doi.org/10.3389/fimmu.2020.621537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886804PMC
June 2021
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