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An approach based on a dendrimer display of B- and T-cell epitopes relevant for antibody induction has been shown to be effective as a foot-and-mouth disease (FMD) vaccine. B2T dendrimers combining two copies of the major FMD virus (FMDV) type O B-cell epitope (capsid proteinVP1 (140–158)) covalently linked to a heterotypic T-cell epitope from non-structural protein 3A (21–35), henceforth B2T-3A, has previously been shown to elicit high neutralizing antibody (nAb) titers and IFN-γ-producing cells in both mice and pigs. Here, we provide evidence that the B- and T-cell epitopes need to be tethered to a single molecular platform for successful T-cell help, leading to efficient nAb induction in mice. In addition, mice immunized with a non-covalent mixture of B2T-3A dendrimers containing the B-cell epitopes of FMDV types O and C induced similarly high nAb levels against both serotypes, opening the way for a multivalent vaccine platform against a variety of serologically different FMDVs. These findings are relevant for the design of vaccine strategies based on B- and T-cell epitope combinations.
Rodrigo Cañas-Arranz; Patricia de León; Sira Defaus; Elisa Torres; Mar Forner; María Bustos; David Andreu; Esther Blanco; Francisco Sobrino. Immunogenicity of Foot-and-Mouth Disease Virus Dendrimer Peptides: Need for a T-Cell Epitope and Ability to Elicit Heterotypic Responses. Molecules 2021, 26, 4714 .
AMA StyleRodrigo Cañas-Arranz, Patricia de León, Sira Defaus, Elisa Torres, Mar Forner, María Bustos, David Andreu, Esther Blanco, Francisco Sobrino. Immunogenicity of Foot-and-Mouth Disease Virus Dendrimer Peptides: Need for a T-Cell Epitope and Ability to Elicit Heterotypic Responses. Molecules. 2021; 26 (16):4714.
Chicago/Turabian StyleRodrigo Cañas-Arranz; Patricia de León; Sira Defaus; Elisa Torres; Mar Forner; María Bustos; David Andreu; Esther Blanco; Francisco Sobrino. 2021. "Immunogenicity of Foot-and-Mouth Disease Virus Dendrimer Peptides: Need for a T-Cell Epitope and Ability to Elicit Heterotypic Responses." Molecules 26, no. 16: 4714.
Mesoporous silica nanoparticles have drawn increasing attention as promising candidates in vaccine delivery. Previous studies evaluating silica-based vaccine delivery systems concentrated largely on macromolecular antigens, such as inactivated whole viruses. In this study, we synthesized dendritic mesoporous silica nanoparticles (DMSNs), and we evaluated their effectiveness as delivery platforms for peptide-based subunit vaccines. We encapsulated and tested in vivo an earlier reported foot-and-mouth disease virus (FMDV) peptide vaccine (B2T). The [email protected] formulation contained the peptide vaccine and the DMSNs without further need of other compounds neither adjuvants nor emulsions. We measured in vitro a sustained release up to 930 h. [email protected] and [email protected] released 23.7% (135 µg) and 22.8% (132 µg) of the total B2T. The formation of a corona of serum proteins around the DMSNs increased the B2T release up to 61% (348 µg/mg) and 80% (464 µg/mg) for [email protected] and [email protected] In vitro results point out to a longer sustained release, assisted by the formation of a protein corona around DMSNs, compared to the reference formulation (i.e., B2T emulsified in Montanide). We further confirmed in vivo immunogenicity of [email protected] in a particle size-dependent manner. Since [email protected] elicited specific immune responses in mice with high IgG production like the reference [email protected]™, self-adjuvant properties of the DMSNs could be ascribed. Our results display DMSNs as efficacious nanocarriers for peptide-based vaccine administration.
Weiteng An; Sira Defaus; David Andreu; Pilar Rivera-Gil. In Vivo Sustained Release of Peptide Vaccine Mediated by Dendritic Mesoporous Silica Nanocarriers. Frontiers in Immunology 2021, 12, 1 .
AMA StyleWeiteng An, Sira Defaus, David Andreu, Pilar Rivera-Gil. In Vivo Sustained Release of Peptide Vaccine Mediated by Dendritic Mesoporous Silica Nanocarriers. Frontiers in Immunology. 2021; 12 ():1.
Chicago/Turabian StyleWeiteng An; Sira Defaus; David Andreu; Pilar Rivera-Gil. 2021. "In Vivo Sustained Release of Peptide Vaccine Mediated by Dendritic Mesoporous Silica Nanocarriers." Frontiers in Immunology 12, no. : 1.
Passing through the blood-brain barrier (BBB) to treat neurological conditions is one of the main hurdles in modern medicine. Many drugs with promising in vitro profiles become ineffective in vivo due to BBB restrictive permeability. In particular, this includes drugs such as antiviral porphyrins, with the ability to fight brain-resident viruses causing diseases such as HIV-associated neurocognitive disorders (HAND). In the last two decades, BBB shuttles, particularly peptide-based ones, have shown promise in carrying various payloads across the BBB. Thus, peptide–drug conjugates (PDCs) formed by covalent attachment of a BBB peptide shuttle and an antiviral drug may become key therapeutic tools in treating neurological disorders of viral origin. In this study, we have used various approaches (guanidinium, phosphonium, and carbodiimide-based couplings) for on-resin synthesis of new peptide–porphyrin conjugates (PPCs) with BBB-crossing and potential antiviral activity. After careful fine-tuning of the synthetic chemistry, DIC/oxyma has emerged as a preferred method, by which 14 different PPCs have been made and satisfactorily characterized. The PPCs are prepared by coupling a porphyrin carboxyl group to an amino group (either N-terminal or a Lys side chain) of the peptide shuttle and show effective in vitro BBB translocation ability, low cytotoxicity toward mouse brain endothelial cells, and low hemolytic activity. Three of the PPCs, MP-P5, P4-MP, and P4-L-MP, effectively inhibiting HIV infectivity in vitro, stand out as most promising. Their efficacy against other brain-targeting viruses (Dengue, Zika, and SARS-CoV-2) is currently under evaluation, with preliminary results confirming that PPCs are a promising strategy to treat viral brain infections.
Diogo A. Mendonça; Mariët Bakker; Christine Cruz-Oliveira; Vera Neves; Maria Angeles Jiménez; Sira Defaus; Marco Cavaco; Ana Salomé Veiga; Iris Cadima-Couto; Miguel A. R. B. Castanho; David Andreu; Toni Todorovski. Penetrating the Blood-Brain Barrier with New Peptide–Porphyrin Conjugates Having anti-HIV Activity. Bioconjugate Chemistry 2021, 32, 1067 -1077.
AMA StyleDiogo A. Mendonça, Mariët Bakker, Christine Cruz-Oliveira, Vera Neves, Maria Angeles Jiménez, Sira Defaus, Marco Cavaco, Ana Salomé Veiga, Iris Cadima-Couto, Miguel A. R. B. Castanho, David Andreu, Toni Todorovski. Penetrating the Blood-Brain Barrier with New Peptide–Porphyrin Conjugates Having anti-HIV Activity. Bioconjugate Chemistry. 2021; 32 (6):1067-1077.
Chicago/Turabian StyleDiogo A. Mendonça; Mariët Bakker; Christine Cruz-Oliveira; Vera Neves; Maria Angeles Jiménez; Sira Defaus; Marco Cavaco; Ana Salomé Veiga; Iris Cadima-Couto; Miguel A. R. B. Castanho; David Andreu; Toni Todorovski. 2021. "Penetrating the Blood-Brain Barrier with New Peptide–Porphyrin Conjugates Having anti-HIV Activity." Bioconjugate Chemistry 32, no. 6: 1067-1077.
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.
Mar Forner; Rodrigo Cañas-Arranz; Sira Defaus; Patricia de León; Miguel Rodríguez-Pulido; Llilianne Ganges; Esther Blanco; Francisco Sobrino; David Andreu. Peptide-Based Vaccines: Foot-and-Mouth Disease Virus, a Paradigm in Animal Health. Vaccines 2021, 9, 477 .
AMA StyleMar Forner, Rodrigo Cañas-Arranz, Sira Defaus, Patricia de León, Miguel Rodríguez-Pulido, Llilianne Ganges, Esther Blanco, Francisco Sobrino, David Andreu. Peptide-Based Vaccines: Foot-and-Mouth Disease Virus, a Paradigm in Animal Health. Vaccines. 2021; 9 (5):477.
Chicago/Turabian StyleMar Forner; Rodrigo Cañas-Arranz; Sira Defaus; Patricia de León; Miguel Rodríguez-Pulido; Llilianne Ganges; Esther Blanco; Francisco Sobrino; David Andreu. 2021. "Peptide-Based Vaccines: Foot-and-Mouth Disease Virus, a Paradigm in Animal Health." Vaccines 9, no. 5: 477.
The activation of cannabinoid CB1 receptors (CB1R) by Δ9-tetrahydrocannabinol (THC), the main component of Cannabis sativa, induces analgesia. CB1R activation, however, also causes cognitive impairment via the serotonin 5HT2A receptor (5HT2AR), a component of a CB1R–5HT2AR heteromer, posing a serious drawback for cannabinoid therapeutic use. We have shown that peptides reproducing CB1R transmembrane (TM) helices 5 and 6, fused to a cell-penetrating sequence (CPP), can alter the structure of the CB1R–5HT2AR heteromer and avert THC cognitive impairment while preserving analgesia. Here, we report the optimization of these prototypes into drug-like leads by (i) shortening the TM5, TM6, and CPP sequences, without losing the ability to disturb the CB1R–5HT2AR heteromer, and (ii) extensive sequence remodeling to achieve protease resistance and blood–brain barrier penetration. Our efforts have culminated in the identification of an ideal candidate for cannabis-based pain management, an orally active 16-residue peptide preserving THC-induced analgesia.
Maria Gallo; Estefanía Moreno; Sira Defaus; Antonio Ortega-Alvaro; Angel Gonzalez; Patricia Robledo; Marco Cavaco; Vera Neves; Miguel A. R. B. Castanho; Vicent Casadó; Leonardo Pardo; Rafael Maldonado; David Andreu. Orally Active Peptide Vector Allows Using Cannabis to Fight Pain While Avoiding Side Effects. Journal of Medicinal Chemistry 2021, 64, 6937 -6948.
AMA StyleMaria Gallo, Estefanía Moreno, Sira Defaus, Antonio Ortega-Alvaro, Angel Gonzalez, Patricia Robledo, Marco Cavaco, Vera Neves, Miguel A. R. B. Castanho, Vicent Casadó, Leonardo Pardo, Rafael Maldonado, David Andreu. Orally Active Peptide Vector Allows Using Cannabis to Fight Pain While Avoiding Side Effects. Journal of Medicinal Chemistry. 2021; 64 (10):6937-6948.
Chicago/Turabian StyleMaria Gallo; Estefanía Moreno; Sira Defaus; Antonio Ortega-Alvaro; Angel Gonzalez; Patricia Robledo; Marco Cavaco; Vera Neves; Miguel A. R. B. Castanho; Vicent Casadó; Leonardo Pardo; Rafael Maldonado; David Andreu. 2021. "Orally Active Peptide Vector Allows Using Cannabis to Fight Pain While Avoiding Side Effects." Journal of Medicinal Chemistry 64, no. 10: 6937-6948.
The tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumour necrosis factor ligand family and has been shown to be overexpressed in tumoral cells together with the fibroblast growth factor–inducible 14 (Fn14) receptor. TWEAK-Fn14 interaction triggers a set of intracellular pathways responsible for tumour cell invasion and migration, as well as proliferation and angiogenesis. Hence, modulation of the TWEAK-Fn14 interaction is an important therapeutic goal. The targeting of protein-protein interactions by external agents, e.g., drugs, remains a substantial challenge. Given their intrinsic features, as well as recent advances that improve their pharmacological profiles, peptides have arisen as promising agents in this regard. Here, we report, by in silico structural design validated by cell-based and in vitro assays, the discovery of four peptides able to target TWEAK. Our results show that, when added to TWEAK-dependent cellular cultures, peptides cause a down-regulation of genes that are part of TWEAK-Fn14 signalling pathway. The direct, physical interaction between the peptides and TWEAK was further elucidated in an in vitro assay which confirmed that the bioactivity shown in cell-based assays was due to the targeting of TWEAK. The results presented here are framed within early pre-clinical drug development and therefore these peptide hits represent a starting point for the development of novel therapeutic agents. Our approach exemplifies the powerful combination of in silico and experimental efforts to quickly identify peptides with desirable traits.
Miriam Badia-Villanueva; Sira Defaus; Ruben Foj; David Andreu; Baldo Oliva; Angels Sierra; Narcis Fernandez-Fuentes. Evaluation of Computationally Designed Peptides Against TWEAK, a Cytokine of the Tumour Necrosis Factor Ligand Family. International Journal of Molecular Sciences 2021, 22, 1066 .
AMA StyleMiriam Badia-Villanueva, Sira Defaus, Ruben Foj, David Andreu, Baldo Oliva, Angels Sierra, Narcis Fernandez-Fuentes. Evaluation of Computationally Designed Peptides Against TWEAK, a Cytokine of the Tumour Necrosis Factor Ligand Family. International Journal of Molecular Sciences. 2021; 22 (3):1066.
Chicago/Turabian StyleMiriam Badia-Villanueva; Sira Defaus; Ruben Foj; David Andreu; Baldo Oliva; Angels Sierra; Narcis Fernandez-Fuentes. 2021. "Evaluation of Computationally Designed Peptides Against TWEAK, a Cytokine of the Tumour Necrosis Factor Ligand Family." International Journal of Molecular Sciences 22, no. 3: 1066.
Conjugation of TP10, a cell-penetrating peptide with intrinsic antimalarial activity, to the well-known antimalarial drugs chloroquine and primaquine has been previously shown to enhance the peptide’s action against, respectively, blood- and liver-stage malaria parasites. Yet, this was achieved at the cost of a significant increase in haemolytic activity, as fluorescence microscopy and flow cytometry studies showed the conjugates to be more haemolytic for non-infected than for Plasmodium-infected red blood cells. To gain further insight into how these conjugates distinctively bind, and likely disrupt, membranes of both Plasmodium-infected and non-infected erythrocytes, we used dynamic light scattering and surface plasmon resonance to study the interactions of two representative conjugates and their parent compounds with lipid model membranes. Results obtained are herein reported and confirm that a strong membrane-disruptive character underlies the haemolytic properties of these conjugates, thus hampering their ability to exert selective antimalarial action.
Luísa Aguiar; Marina Pinheiro; Ana Rute Neves; Nuno Vale; Sira Defaus; David Andreu; Salette Reis; Paula Gomes. Insights into the Membranolytic Activity of Antimalarial Drug-Cell Penetrating Peptide Conjugates. Membranes 2020, 11, 4 .
AMA StyleLuísa Aguiar, Marina Pinheiro, Ana Rute Neves, Nuno Vale, Sira Defaus, David Andreu, Salette Reis, Paula Gomes. Insights into the Membranolytic Activity of Antimalarial Drug-Cell Penetrating Peptide Conjugates. Membranes. 2020; 11 (1):4.
Chicago/Turabian StyleLuísa Aguiar; Marina Pinheiro; Ana Rute Neves; Nuno Vale; Sira Defaus; David Andreu; Salette Reis; Paula Gomes. 2020. "Insights into the Membranolytic Activity of Antimalarial Drug-Cell Penetrating Peptide Conjugates." Membranes 11, no. 1: 4.
Dendrimer peptides are promising vaccine candidates against the foot-and-mouth disease virus (FMDV). Several B-cell epitope (B2T) dendrimers, harboring a major FMDV antigenic B-cell site in VP1 protein, are covalently linked to heterotypic T-cell epitopes from 3A and/or 3D proteins, and elicited consistent levels of neutralizing antibodies and IFN-γ-producing cells in pigs. To address the contribution of the highly polymorphic nature of the porcine MHC (SLA, swine leukocyte antigen) on the immunogenicity of B2T dendrimers, low-resolution (Lr) haplotyping was performed. We looked for possible correlations between particular Lr haplotypes with neutralizing antibody and T-cell responses induced by B2T peptides. In this study, 63 pigs immunized with B2T dendrimers and 10 non-immunized (control) animals are analyzed. The results reveal a robust significant correlation between SLA class-II Lr haplotypes and the T-cell response. Similar correlations of T-cell response with SLA class-I Lr haplotypes, and between B-cell antibody response and SLA class-I and SLA class-II Lr haplotypes, were only found when the sample was reduced to animals with Lr haplotypes represented more than once. These results support the contribution of SLA class-II restricted T-cells to the magnitude of the T-cell response and to the antibody response evoked by the B2T dendrimers, being of potential value for peptide vaccine design against FMDV.
Patricia De León; Rodrigo Cañas-Arranz; Yago Saez; Mar Forner; Sira Defaus; Dolores Cuadra; María J. Bustos; Elisa Torres; David Andreu; Esther Blanco; Francisco Sobrino; Sabine E. Hammer. Association of Porcine Swine Leukocyte Antigen (SLA) Haplotypes with B- and T-Cell Immune Response to Foot-and-Mouth Disease Virus (FMDV) Peptides. Vaccines 2020, 8, 513 .
AMA StylePatricia De León, Rodrigo Cañas-Arranz, Yago Saez, Mar Forner, Sira Defaus, Dolores Cuadra, María J. Bustos, Elisa Torres, David Andreu, Esther Blanco, Francisco Sobrino, Sabine E. Hammer. Association of Porcine Swine Leukocyte Antigen (SLA) Haplotypes with B- and T-Cell Immune Response to Foot-and-Mouth Disease Virus (FMDV) Peptides. Vaccines. 2020; 8 (3):513.
Chicago/Turabian StylePatricia De León; Rodrigo Cañas-Arranz; Yago Saez; Mar Forner; Sira Defaus; Dolores Cuadra; María J. Bustos; Elisa Torres; David Andreu; Esther Blanco; Francisco Sobrino; Sabine E. Hammer. 2020. "Association of Porcine Swine Leukocyte Antigen (SLA) Haplotypes with B- and T-Cell Immune Response to Foot-and-Mouth Disease Virus (FMDV) Peptides." Vaccines 8, no. 3: 513.
A broadly protective and biosafe vaccine against foot-and-mouth disease virus (FMDV) remains an unmet need in the animal health sector. We have previously reported solid protection against serotype O FMDV afforded by dendrimeric peptide structures harboring virus-specific B- and T-cell epitopes, and also shown such type of multivalent presentations to be advantageous over simple B-T-epitope linear juxtaposition. Chemically, our vaccine platforms are modular constructions readily made from specified B- and T-cell epitope precursor peptides that are conjugated in solution. With the aim of developing an improved version of our formulations to be used for on-demand vaccine applications, we evaluate in this study a novel design for epitope presentation to the immune system based on a multiple antigen peptide (MAP) containing six immunologically relevant motifs arranged in dendrimeric fashion (named B2T-TB2). Interestingly, two B2T units fused tail-to-tail into a single homodimer platform elicited higher B- and T-cell specific responses than former candidates, with immunization scores remaining stable even after 4 months. Moreover, this macromolecular assembly shows consistent immune response in swine, the natural FMDV host, at reduced dose. Thus, our versatile, immunogenic prototype can find application in the development of peptide-based vaccine candidates for various therapeutic uses using safer and more efficacious vaccination regimens.
Sira Defaus; Mar Forner; Rodrigo Cañas-Arranz; Patricia De León; María J. Bustos; Miguel Rodríguez-Pulido; Esther Blanco; Francisco Sobrino; David Andreu. Designing Functionally Versatile, Highly Immunogenic Peptide-Based Multiepitopic Vaccines against Foot-and-Mouth Disease Virus. Vaccines 2020, 8, 406 .
AMA StyleSira Defaus, Mar Forner, Rodrigo Cañas-Arranz, Patricia De León, María J. Bustos, Miguel Rodríguez-Pulido, Esther Blanco, Francisco Sobrino, David Andreu. Designing Functionally Versatile, Highly Immunogenic Peptide-Based Multiepitopic Vaccines against Foot-and-Mouth Disease Virus. Vaccines. 2020; 8 (3):406.
Chicago/Turabian StyleSira Defaus; Mar Forner; Rodrigo Cañas-Arranz; Patricia De León; María J. Bustos; Miguel Rodríguez-Pulido; Esther Blanco; Francisco Sobrino; David Andreu. 2020. "Designing Functionally Versatile, Highly Immunogenic Peptide-Based Multiepitopic Vaccines against Foot-and-Mouth Disease Virus." Vaccines 8, no. 3: 406.
For decades, natural products in general and snake venoms (SV) in particular have been a rich source of bioactive compounds for drug discovery, and they remain a promising substrate for therapeutic development. Currently, a handful of SV-based drugs for diagnosis and treatment of various cardiovascular disorders and blood abnormalities are on the market. Likewise, far more SV compounds and their mimetics are under investigation today for diverse therapeutic applications, including antibiotic-resistant bacteria and cancer. In this review, we analyze the state of the art regarding SV-derived compounds with therapeutic potential, focusing on the development of antimicrobial and anticancer drugs. Specifically, information about SV peptides experimentally validated or predicted to act as antimicrobial and anticancer peptides (AMPs and ACPs, respectively) has been collected and analyzed. Their principal activities both in vitro and in vivo, structures, mechanisms of action, and attempts at sequence optimization are discussed in order to highlight their potential as drug leads.
Clara Pérez-Peinado; Sira Defaus; David Andreu. Hitchhiking with Nature: Snake Venom Peptides to Fight Cancer and Superbugs. Toxins 2020, 12, 255 .
AMA StyleClara Pérez-Peinado, Sira Defaus, David Andreu. Hitchhiking with Nature: Snake Venom Peptides to Fight Cancer and Superbugs. Toxins. 2020; 12 (4):255.
Chicago/Turabian StyleClara Pérez-Peinado; Sira Defaus; David Andreu. 2020. "Hitchhiking with Nature: Snake Venom Peptides to Fight Cancer and Superbugs." Toxins 12, no. 4: 255.
Foot‐and‐mouth disease virus (FMDV) causes a widely extended contagious disease of livestock. We have previously reported that a synthetic dendrimeric peptide, termed B2T(mal), consisting of two copies of a B‐cell epitope [VP1(140‐158)] linked through maleimide groups to a T‐cell epitope [3A(21‐35)] of FMDV, elicits potent B‐ and T‐cell specific responses and confers solid protection in pigs to type O FMDV challenge. Longer duration of the protective response as well as the possibility of inducing protection after a single dose are important requirements for an efficient FMD vaccine. Herein, we show that administration of two doses of B2T(mal) elicited high levels of specific total IgGs and neutralizing antibodies that lasted 4‐5 months after the peptide boost. Additionally, concomitant levels of IFN‐γ producing specific T‐cells were observed. Immunization with two doses of B2T(mal) conferred a long‐lasting reduced susceptibility to FMDV infection, up to 136 days (19/20 weeks) post‐boost. Remarkably, a similar duration of the protective response was achieved by a single dose of B2T(mal). The effect on the B2T(mal) vaccine of RNA transcripts derived from non‐coding regions in the FMDV genome, known to enhance the immune response and protection induced by a conventional inactivated vaccine, was also analyzed. The contribution of our results to the development of FMD dendrimeric vaccines is discussed.
Rodrigo Cañas‐Arranz; Mar Forner; Sira Defaus; Miguel Rodríguez‐Pulido; Patricia De León; Elisa Torres; María J. Bustos; Belén Borrego; Margarita Sáiz; Esther Blanco; David Andreu; Francisco Sobrino. A bivalent B‐cell epitope dendrimer peptide can confer long‐lasting immunity in swine against foot‐and‐mouth disease. Transboundary and Emerging Diseases 2020, 67, 1614 -1622.
AMA StyleRodrigo Cañas‐Arranz, Mar Forner, Sira Defaus, Miguel Rodríguez‐Pulido, Patricia De León, Elisa Torres, María J. Bustos, Belén Borrego, Margarita Sáiz, Esther Blanco, David Andreu, Francisco Sobrino. A bivalent B‐cell epitope dendrimer peptide can confer long‐lasting immunity in swine against foot‐and‐mouth disease. Transboundary and Emerging Diseases. 2020; 67 (4):1614-1622.
Chicago/Turabian StyleRodrigo Cañas‐Arranz; Mar Forner; Sira Defaus; Miguel Rodríguez‐Pulido; Patricia De León; Elisa Torres; María J. Bustos; Belén Borrego; Margarita Sáiz; Esther Blanco; David Andreu; Francisco Sobrino. 2020. "A bivalent B‐cell epitope dendrimer peptide can confer long‐lasting immunity in swine against foot‐and‐mouth disease." Transboundary and Emerging Diseases 67, no. 4: 1614-1622.
Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals whose control relies on efficient vaccination. We have reported that dendrimer peptide B2T, with two copies of FMDV B-cell epitope VP1 (136–154) linked through maleimide units to T-cell epitope 3A (21–35)], elicits potent B- and T-cell specific responses and confers solid protection in pigs to type-O FMDV challenge after two doses of peptide. Herein we now show that B2T evokes specific protective immune responses after administration of a single dose of either 2 or 0.5 mg of peptide. High titers of ELISA and neutralizing antibodies against FMDV were detectable at day 15 post-immunization. Likewise, activated T cells and induced IFN-γ response to in vitro recall with FMDV peptides were also detected by the same day. Further, in 70% of B2T-vaccinated pigs, full protection—no clinical signs of disease—was observed upon virus challenge at day 25 post-immunization. These results strengthen the potential of B2T as a safe, cost-effective candidate vaccine conferring adequate protection against FMDV with a single dose. The finding is particularly relevant to emergency scenarios permitting only a single shot immunization.
Rodrigo Cañas-Arranz; Mar Forner; Sira Defaus; Patricia De León; María J. Bustos; Elisa Torres; Francisco Sobrino; David Andreu; Esther Blanco. A Single Dose of Dendrimer B2T Peptide Vaccine Partially Protects Pigs against Foot-and-Mouth Disease Virus Infection. Vaccines 2020, 8, 19 .
AMA StyleRodrigo Cañas-Arranz, Mar Forner, Sira Defaus, Patricia De León, María J. Bustos, Elisa Torres, Francisco Sobrino, David Andreu, Esther Blanco. A Single Dose of Dendrimer B2T Peptide Vaccine Partially Protects Pigs against Foot-and-Mouth Disease Virus Infection. Vaccines. 2020; 8 (1):19.
Chicago/Turabian StyleRodrigo Cañas-Arranz; Mar Forner; Sira Defaus; Patricia De León; María J. Bustos; Elisa Torres; Francisco Sobrino; David Andreu; Esther Blanco. 2020. "A Single Dose of Dendrimer B2T Peptide Vaccine Partially Protects Pigs against Foot-and-Mouth Disease Virus Infection." Vaccines 8, no. 1: 19.
In 1988, two unrelated papers reported the discovery of peptide vectors with innate cell translocation properties, setting the ground for a new area of research that over the years has grown into considerable therapeutic potential. The vectors, named cell-penetrating peptides (CPPs), constitute a now large and diversified family, sharing the extraordinary ability to diffuse unaltered across cell membranes while ferrying diverse associated cargos. Such properties have made CPPs ideal tools for delivery of nucleic acids, proteins and other therapeutic/diagnostic molecules to cells and tissues via covalent conjugation or complexation. This year 2018 marks the 30th anniversary of a peptide research landmark opening new perspectives in drug delivery. Given its vastness, exhaustive coverage of the main features and accomplishments in the CPP field is virtually impossible. Hence this manuscript, after saluting the above 30th jubilee, focuses by necessity on the most recent contributions, providing a comprehensive list of recognized CPPs and their latest-reported applications over the last two years. In addition, it thoroughly reviews three areas of peptide vector research of particular interest to us, namely (i) efficient transport of low-bioavailability drugs into the brain; (ii) CPP-delivered disruptors of G protein-coupled receptor (GPCRs) heteromers related to several disorders, and (iii) CPP-mediated delivery of useful but poorly internalized drugs into parasites.
Maria Gallo; Sira Defaus; David Andreu. 1988–2018: Thirty years of drug smuggling at the nano scale. Challenges and opportunities of cell-penetrating peptides in biomedical research. Archives of Biochemistry and Biophysics 2018, 661, 74 -86.
AMA StyleMaria Gallo, Sira Defaus, David Andreu. 1988–2018: Thirty years of drug smuggling at the nano scale. Challenges and opportunities of cell-penetrating peptides in biomedical research. Archives of Biochemistry and Biophysics. 2018; 661 ():74-86.
Chicago/Turabian StyleMaria Gallo; Sira Defaus; David Andreu. 2018. "1988–2018: Thirty years of drug smuggling at the nano scale. Challenges and opportunities of cell-penetrating peptides in biomedical research." Archives of Biochemistry and Biophysics 661, no. : 74-86.
Seminal plasma proteins are relevant for sperm functionality and some appear responsible for establishing sperm interactions with the various environments along the female genital tract towards the oocyte. In recent years, research has focused on characterizing the role of these proteins in the context of reproductive biology, fertility diagnostics and treatment of related problems. Herein, we focus on the main protein of bovine seminal plasma, PDC-109 (BSP-A1/-A2), which by virtue of its lectin properties is involved in fertilization. By means of surface plasmon resonance, the interaction of PDC-109 with a panel of the most relevant glycosidic epitopes of mammals has been qualitatively and quantitatively characterized, and a higher affinity for carbohydrates containing fucose has been observed, in line with previous studies. Additionally, using the orthogonal technique of Carbohydrate REcognition Domain EXcision-Mass Spectrometry (CREDEX-MS), the recognition domain of the interaction complexes between PDC-109 and all fucosylated disaccharides [(Fuc-α1,(3,4,6)-GlcNAc)] has been defined, revealing the specific glycotope and the peptide domain likely to act as the PDC-109 carbohydrate binding site.
Sira Defaus; Manuel Avilés; David Andreu; Ricardo Gutierrez-Gallego. Lectin-Binding Specificity of the Fertilization-Relevant Protein PDC-109 by Means of Surface Plasmon Resonance and Carbohydrate REcognition Domain EXcision-Mass Spectrometry. International Journal of Molecular Sciences 2018, 19, 1076 .
AMA StyleSira Defaus, Manuel Avilés, David Andreu, Ricardo Gutierrez-Gallego. Lectin-Binding Specificity of the Fertilization-Relevant Protein PDC-109 by Means of Surface Plasmon Resonance and Carbohydrate REcognition Domain EXcision-Mass Spectrometry. International Journal of Molecular Sciences. 2018; 19 (4):1076.
Chicago/Turabian StyleSira Defaus; Manuel Avilés; David Andreu; Ricardo Gutierrez-Gallego. 2018. "Lectin-Binding Specificity of the Fertilization-Relevant Protein PDC-109 by Means of Surface Plasmon Resonance and Carbohydrate REcognition Domain EXcision-Mass Spectrometry." International Journal of Molecular Sciences 19, no. 4: 1076.
José Alejandro Bohórquez; Sira Defaus; Sara Muñoz-González; Marta Perez-Simó; Rosa Rosell; Lorenzo Fraile; Francisco Sobrino; David Andreu; Llilianne Ganges. A bivalent dendrimeric peptide bearing a T-cell epitope from foot-and-mouth disease virus protein 3A improves humoral response against classical swine fever virus. Virus Research 2017, 238, 8 -12.
AMA StyleJosé Alejandro Bohórquez, Sira Defaus, Sara Muñoz-González, Marta Perez-Simó, Rosa Rosell, Lorenzo Fraile, Francisco Sobrino, David Andreu, Llilianne Ganges. A bivalent dendrimeric peptide bearing a T-cell epitope from foot-and-mouth disease virus protein 3A improves humoral response against classical swine fever virus. Virus Research. 2017; 238 ():8-12.
Chicago/Turabian StyleJosé Alejandro Bohórquez; Sira Defaus; Sara Muñoz-González; Marta Perez-Simó; Rosa Rosell; Lorenzo Fraile; Francisco Sobrino; David Andreu; Llilianne Ganges. 2017. "A bivalent dendrimeric peptide bearing a T-cell epitope from foot-and-mouth disease virus protein 3A improves humoral response against classical swine fever virus." Virus Research 238, no. : 8-12.
Glycan-protein interactions play a key role in mammalian fertilization, but data on the composition and identities of protein complexes involved in fertilization events are scarce, with the added complication that the glycans in such interactions tend to differ among species. In this study we have used a bovine model to detect, characterize and identify sperm lectins relevant in fertilization. Given the complexity of the sperm-toward-egg journey, two important aspects of the process, both primarily mediated by protein-sugar interactions, have been addressed: (1) formation of the sperm reservoir in the oviductal epithelium, and (2) gamete recognition (oocyte-sperm interaction). Using whole sperm cells and a novel affinity capture method, several groups of proteins with different glycan specificities, including 58 hitherto unreported as lectins, have been identified in sperm surface, underscoring both the efficacy of our selective approach and the complex composition and function of sperm. Based on these results and previous data, we suggest that sperm surface proteins play significant roles in fertilization events such as membrane remodeling, transport, protection and function, thus supporting the hypothesis that rather than a simple lock-and-key model, mammalian fertilization relies on a complex interactome involving multiple ligands/receptors and recognition/binding events.
Sira Defaus; Manuel Avilés; David Andreu; Ricardo Gutiérrez-Gallego. Identification of Bovine Sperm Surface Proteins Involved in Carbohydrate-mediated Fertilization Interactions. Molecular & Cellular Proteomics 2016, 15, 2236 -2251.
AMA StyleSira Defaus, Manuel Avilés, David Andreu, Ricardo Gutiérrez-Gallego. Identification of Bovine Sperm Surface Proteins Involved in Carbohydrate-mediated Fertilization Interactions. Molecular & Cellular Proteomics. 2016; 15 (7):2236-2251.
Chicago/Turabian StyleSira Defaus; Manuel Avilés; David Andreu; Ricardo Gutiérrez-Gallego. 2016. "Identification of Bovine Sperm Surface Proteins Involved in Carbohydrate-mediated Fertilization Interactions." Molecular & Cellular Proteomics 15, no. 7: 2236-2251.
Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. We have reported (Cubillos et al., 2008) that a synthetic dendrimeric peptide consisting of four copies of a B-cell epitope [VP1(136-154)] linked through thioether bonds to a T-cell epitope [3A(21-35)] of FMDV [B4T(thi)] elicits potent B- and T-cell specific responses and confers solid protection in pigs to type C FMDV challenge. Herein we show that downsized versions of this peptide bearing two copies of a B-cell epitope from a type O isolate and using thioether [B2T(thi)] or maleimide [B2T(mal)] conjugation chemistries for their synthesis elicited in swine similar or higher B and T-cell specific responses than tetravalent B4T(thi). Moreover, while partial protection was observed in animals immunized with B4T(thi) (60%) and B2T(thi) (80%), B2T(mal) conferred full (100%) protection against FMDV challenge, associated to high levels of circulating IgG2 and mucosal IgGA, and entirely prevented virus shedding. Interestingly, B2T(mal) is also the most advantageous option in terms of synthetic practicality. Taken together, the results reported here point out to B2T(mal) as a highly valuable, cost-effective FMDV candidate vaccine.
Esther Blanco; Beatriz Guerra; Beatriz G. de la Torre; Sira Defaus; Aldo Dekker; David Andreu; Francisco Sobrino. Full protection of swine against foot-and-mouth disease by a bivalent B-cell epitope dendrimer peptide. Antiviral Research 2016, 129, 74 -80.
AMA StyleEsther Blanco, Beatriz Guerra, Beatriz G. de la Torre, Sira Defaus, Aldo Dekker, David Andreu, Francisco Sobrino. Full protection of swine against foot-and-mouth disease by a bivalent B-cell epitope dendrimer peptide. Antiviral Research. 2016; 129 ():74-80.
Chicago/Turabian StyleEsther Blanco; Beatriz Guerra; Beatriz G. de la Torre; Sira Defaus; Aldo Dekker; David Andreu; Francisco Sobrino. 2016. "Full protection of swine against foot-and-mouth disease by a bivalent B-cell epitope dendrimer peptide." Antiviral Research 129, no. : 74-80.
Interest in powerful, nanosized tools to analyze in detail glycan–protein interactions has increased significantly over recent years. Here, we report two complementary approaches to characterize such interactions with high sensitivity, low sample consumption, and without the need for sample labeling, namely, surface plasmon resonance (SPR) and an approach that combines limited proteolysis and mass spectrometry. Combination of these two approaches to investigate glycan–protein interactions allows (1) to characterize interactions through kinetic and thermodynamic parameters, (2) to capture efficiently the carbohydrate-binding protein, and (3) to identify the interacted protein and its carbohydrate binding site by mass spectrometry. As a proof of principle, the interaction of the galactose-specific legume lectin Erythrina cristagalli agglutinin with several sugars has been characterized in-depth by means of these two approaches.
Carmen Jiménez-Castells; Sira Defaus; Adrian Moise; Michael Przbylski; David Andreu; Ricardo Gutiérrez-Gallego. Surface-Based and Mass Spectrometric Approaches to Deciphering Sugar–Protein Interactions in a Galactose-Specific Agglutinin. Analytical Chemistry 2012, 84, 6515 -6520.
AMA StyleCarmen Jiménez-Castells, Sira Defaus, Adrian Moise, Michael Przbylski, David Andreu, Ricardo Gutiérrez-Gallego. Surface-Based and Mass Spectrometric Approaches to Deciphering Sugar–Protein Interactions in a Galactose-Specific Agglutinin. Analytical Chemistry. 2012; 84 (15):6515-6520.
Chicago/Turabian StyleCarmen Jiménez-Castells; Sira Defaus; Adrian Moise; Michael Przbylski; David Andreu; Ricardo Gutiérrez-Gallego. 2012. "Surface-Based and Mass Spectrometric Approaches to Deciphering Sugar–Protein Interactions in a Galactose-Specific Agglutinin." Analytical Chemistry 84, no. 15: 6515-6520.
Glycosylation is probably the most complex secondary gene event that affects the vast majority of proteins in nature resulting in the occurrence of a heterogeneous mixture of glycoforms for a single protein. Many functions are exerted by single monosaccharides, well-defined oligosaccharides, or larger glycans present in these glycoproteins. To unravel these functions it is of the utmost importance to prepare well-defined single glycans conjugated to the underlying aglycon. In this review, the most recent developments are described to address the preparation of carbohydrate-amino acid (glyco-conjugates). Naturally occurring N- and O-linked glycosylation are described and the preparation of non-natural sugar-amino acid linkages are also included.
Carmen Jiménez-Castells; Sira Defaus; David Andreu; Ricardo Gutiérrez-Gallego. Recent progress in the field of neoglycoconjugate chemistry. Biomolecular Concepts 2010, 1, 85 -96.
AMA StyleCarmen Jiménez-Castells, Sira Defaus, David Andreu, Ricardo Gutiérrez-Gallego. Recent progress in the field of neoglycoconjugate chemistry. Biomolecular Concepts. 2010; 1 (1):85-96.
Chicago/Turabian StyleCarmen Jiménez-Castells; Sira Defaus; David Andreu; Ricardo Gutiérrez-Gallego. 2010. "Recent progress in the field of neoglycoconjugate chemistry." Biomolecular Concepts 1, no. 1: 85-96.