Epitopes for Multivalent Vaccines Against Listeria, Mycobacterium and Streptococcus spp: A Novel Role for Glyceraldehyde-3-Phosphate Dehydrogenase

The glycolytic enzyme and bacterial virulence factor of Listeria monocytogenes, the glyceraldehyde-3-phosphate dehydrogenase (GAPDH, Lmo2459), ADP-ribosylated the small GTPase, Rab5a, and blocked phagosome maturation. This inhibitory activity localized within the NAD binding domain of GAPDH at the N-terminal 1?22 peptides, also conferred listeriosis protection when used in dendritic cell-based vaccines. In this study, we explore GAPDH of Listeria, Mycobacterium, and Streptococcus spp. taxonomic groups to search for epitopes that confer broad protection against pathogenic strains of these bacteria. GAPDH multivalent epitopes are selected if they induce inhibitory actions and wide-ranging immune responses. Proteomic isolation of GAPDH from dendritic cells infected with Listeria, Mycobacterium, or Streptococcus confirmed similar enzymatic, Rab5a inhibitory and immune stimulation abilities. We identified by bioinformatics and functional analyses GAPDH N-terminal 1?22 peptides from Listeria, Mycobacterium, and Streptococcus that shared 95% sequence homology, enzymatic activity, and B and T cell immune domains. Sera obtained from patients or mice infected with hypervirulent pathogenic Listeria, Mycobacterium, or Streptococcus presented high levels of anti-GAPDH 1?22 antibodies and Th2 cytokines. Monocyte derived dendritic cells from healthy donors loaded with GAPDH 1?22 peptides from Listeria, Mycobacterium, or Streptococcus showed activation patterns that correspond to cross-immunity abilities. In summary, GAPDH 1?22 peptides appeared as putative candidates to include in multivalent dendritic based vaccine platforms for Listeria, Mycobacterium, or Streptococcus

First computational design using lambda-superstrings and in vivo validation of SARS-CoV-2 vaccine

Coronavirus disease 2019 (COVID-19) is the greatest threat to global health at the present time, and considerable public and private effort is being devoted to fighting this recently emerged disease. Despite the undoubted advances in the development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, uncertainty remains about their future efficacy and the duration of the immunity induced. It is therefore prudent to continue designing and testing vaccines against this pathogen. In this article we computationally designed two candidate vaccines, one monopeptide and one multipeptide, using a technique involving optimizing lambda-superstrings, which was introduced and developed by our research group. We tested the monopeptide vaccine, thus establishing a proof of concept for the validity of the technique. We synthesized a peptide of 22 amino acids in length, corresponding to one of the candidate vaccines, and prepared a dendritic cell (DC) vaccine vector loaded with the 22 amino acids SARS-CoV-2 peptide (positions 50-71) contained in the NTD domain (DC-CoVPSA) of the Spike protein. Next, we tested the immunogenicity, the type of immune response elicited, and the cytokine profile induced by the vaccine, using a non-related bacterial peptide as negative control. Our results indicated that the CoVPSA peptide of the Spike protein elicits noticeable immunogenicity in vivo using a DC vaccine vector and remarkable cellular and humoral immune responses. This DC vaccine vector loaded with the NTD peptide of the Spike protein elicited a predominant Th1-Th17 cytokine profile, indicative of an effective anti-viral response. Finally, we performed a proof of concept experiment in humans that included the following groups: asymptomatic non-active COVID-19 patients, vaccinated volunteers, and control donors that tested negative for SARS-CoV-2. The positive control was the current receptor binding domain epitope of COVID-19 RNA-vaccines. We successfully developed a vaccine candidate technique involving optimizing lambda-superstrings and provided proof of concept in human subjects. We conclude that it is a valid method to decipher the best epitopes of the Spike protein of SARS-CoV-2 to prepare peptide-based vaccines for different vector platforms, including DC vaccines.Luis Martínez and Iker Malaina were supported by the Basque Government, grants IT974-16 and KK-2018/00090 and by the UPV/EHU and Basque Center of Applied Mathematics, grants US18/21 and US21/27. Carmen Alvarez-Dominguez was funded by the Instituto de Salud Carlos III, grants DTS18-00022 and PI19-01580, co-funded in part with European FEDER funds “A new way of making Europe”, the Instituto de Investigación Marqués de Valdecilla, grant INNVAL20/01, and the COST European action ENOVA CA-16231. David Salcines-Cuevas was supported by a predoctoral contract for the BioHealth research program of the Cantabria government. Hector Teran-Navarro salary was supported by the Instituto de Investigación Marqués de Valdecilla, grant INNVAL19/26. Andrea Zeoli was an Erasmus student from the University of Milan “La Statale” (Milan, Italy) performing a stay at IDIVAL.Peer reviewe

Pregnancy Vaccination with Gold Glyco-Nanoparticles Carrying Listeria monocytogenes Peptides Protects against Listeriosis and Brain- and Cutaneous-Associated Morbidities

Listeriosis is a fatal infection for fetuses and newborns with two clinical main morbidities in the neonatal period, meningitis and diffused cutaneous lesions. In this study, we vaccinated pregnant females with two gold glyconanoparticles (GNP) loaded with two peptides, listeriolysin peptide 91–99 (LLO91–99) or glyceraldehyde-3-phosphate dehydrogenase 1–22 peptide (GAPDH1–22). Neonates born to vaccinated mothers were free of bacteria and healthy, while non-vaccinated mice presented clear brain affections and cutaneous diminishment of melanocytes. Therefore, these nanoparticle vaccines are effective measures to offer pregnant mothers at high risk of listeriosis interesting therapies that cross the placenta

Ecología política latinoamericana : pensamiento crítico, diferencia latinoamericana y rearticulación epistémica. Volúmen 2

La Ecología Política de América Latina desde su emergencia se viene constituyendo en una relación activa de permanente intercambio y retroalimentación con los muy diversos movimientos y luchas que protagonizan conflictos en diferentes escalas y circunstancias, recogiendo las críticas a los modelos de desarrollo de vigencia hegemónica y delineando con ellos otros futuros posibles. En este sentido, los dos volúmenes que presentamos mantienen el diálogo sobre los debates epistemológicos de la Ecología Política latinoamericana a la vez que se entrocan con las prácticas teóricas, políticas y territoriales, que han caracterizado a nuestra región. Esta marca de origen, se basa en la convicción del vínculo, por momentos tenso y conflictivo pero también creativo y productivo, entre el imperativo del refinamiento de las herramientas teórico-políticas para asumir el análisis crítico y la construcción sostenida de alternativas frente al saqueo, el despojo y la devastación socio-ambiental. De la Presentación de Catalina Toro Pérez y Facundo Martín