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

Álvarez-Domínguez, Carmen; Salcines-Cuevas, David; Teran-Navarro, Hector; Calderon-Gonzalez, Ricardo; Tobes, Raquel; Garcı́a, Isabel; Grijalvo, Santiago; Paradela, Alberto; Seoane, Asunción; Sangari, Félix J.; Fresno, Manuel; Calvo-Montes, Jorge; Bernal, Inmaculada C. Pérez del Molino; Yañez-Diaz, Sonsoles

doi:10.3389/fcimb.2020.573348

Cited by 6 publications

(13 citation statements)

References 31 publications

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“…While streptococcal infections are the most prevalent ones in Cantabria with annual incidences of 77 cases per 100,000 inhabitants, the incidences of listeriosis and mycobacteria were lower but significant, with 4.4 and 1.41 cases per 100,000 inhabitants, respectively. These annual incidences, together with GAPDH homologies higher than 90%, justified preparing universal vaccines for adults based in a single antigen as GAPDH [23]. 1 Bacterial strains isolated at the Microbiology Department of HUMV from 2014 to 2018, whose GAPDH sequence homologies were higher than 90%.…”

Section: Resultsmentioning

confidence: 99%

“…To explore ADP-ribosylation abilities of GAPDH peptides onto GST-Rab5a, 3 µg of purified protein were incubated with 50 µM NAD-biotin at 37 °C in buffer 2X ADPRT (Tris-ClH 50 mM, pH 7.6, 10 mM ATP, 200 mM MgCl 2 , 20 mM NAD, 2 mM ADP-ribose) and 30 µg of a cytosolic extract of DC in the presence of the following sources: 3 µg of bacterial pathogen extracts (LM, MM or SP), E. coli (Ec) extract or different GAPDH-LM peptides of 22 amino acids, GAPDH 1–22 (L1), GAPDH 23–45 (L2) or GAPDH 315–337 (Lc). Western blots are developed with Streptavidin-HRP [ 19 , 23 , 28 ].…”

Section: Methodsmentioning

confidence: 99%

“…Purification of recombinant proteins was evaluated after SDS-PAGE gels loading 3 µg of protein per lane and Coomasie stain as previously reported by our group [ 7 , 23 ]. Verification of protein purification was evaluated after cutting the bands from gels, TCA precipitation and proteomic identification at the Centro Nacional of Biotechnology (Madrid).…”

Section: Methodsmentioning

confidence: 99%

“…Purification of recombinant proteins was evaluated after SDS-PAGE gels loading 3 µg of protein per lane and Coomasie stain as previously reported by our group [7,23].…”

Section: Recombinant Proteins Purification and Enzymatic And Quality mentioning

confidence: 99%

“…These studies are based on a common virulence factor, the glyceraldehyde-3-phosphate-dehydrogenase (GAPDH). GAPDH is a glycolytic enzyme that in Gram-positive bacteria (i.e., Listeria or Streptococcus) and mycobacteria presents analogous ADP-ribosylating abilities and MHC binding properties, that localized at the N-terminal 22 amino acid peptides (GAPDH 1-22 ) with 98.5% sequence homology [ 19 , 23 ]. Here we explore the possibility that DC vaccines loaded with GAPDH 1–22 peptides of Listeria monocytogenes (GAPDH-L1), Mycobacterium marinum (GAPDH-M1) or Streptococcus pneumoniae (GADPH-S1) acted as universal vaccines against these pathogens.…”

Section: Introductionmentioning

confidence: 99%

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Glyceraldehyde-3-phosphate Dehydrogenase Common Peptides of Listeria monocytogenes, Mycobacterium marinum and Streptococcus pneumoniae as Universal Vaccines

et al. 2021

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Universal vaccines can be prepared with antigens common to different pathogens. In this regard, the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a common virulence factor among pathogenic bacteria of the genera Listeria, Mycobacterium and Streptococcus. Their N-terminal 22 amino acid peptides, GAPDH-L1 (Listeria), GAPDH-M1 (Mycobacterium) and GAPDH-S1 (Streptococcus), share 95–98.55% sequence homology, biochemical and MHC binding abilities and, therefore, are good candidates for universal vaccine designs. Here, we used dendritic cells (DC) as vaccine platforms to test GAPDH epitopes that conferred protection against Listeria monocytogenes, Mycobacterium marinum or Streptococcus pneumoniae in our search of epitopes for universal vaccines. DC loaded with GAPDH-L1, GAPDH-M1 or GAPDH-S1 peptides show high immunogenicity measured by the cellular DTH responses in mice, lacked toxicity and were capable of cross-protection immunity against mice infections with each one of the pathogens. Vaccine efficiency correlated with high titers of anti-GAPDH-L1 antibodies in sera of vaccinated mice, a Th1 cytokine pattern and high frequencies of GAPDH-L1-specific CD4+ and CD8+ T cells and IFN-γ producers in the spleens. We concluded that GAPDH-L1 peptide was the best epitope for universal vaccines in the Listeria, Mycobacterium or Streptococcus taxonomic groups, whose pathogenic strains caused relevant morbidities in adults and especially in the elderly.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Purification of recombinant proteins was evaluated after SDS-PAGE gels loading 3 µg of protein per lane and Coomasie stain as previously reported by our group [7,23].…”

Section: Recombinant Proteins Purification and Enzymatic And Quality mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Glyceraldehyde-3-phosphate Dehydrogenase Common Peptides of Listeria monocytogenes, Mycobacterium marinum and Streptococcus pneumoniae as Universal Vaccines

et al. 2021

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Targeting <em>Plasmodium </em>Population Bottlenecks with Parasite Ligands as Vaccine Antigens

Khan,

Patel,

Patni

et al. 2024

Preprint

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WHO reported an estimated 249 million malaria cases and 608,000 malaria deaths in 85 countries in 2022. A total of 94% of malaria deaths occurred in Africa, 80 % of which were children under 5. In other words, one child dies every minute from malaria. The RTS,S/AS01 malaria vaccine, that uses the Plasmodium falciparum circumsporozoite protein (CSP) to target sporozoite infection of the liver, achieved modest efficacy. The Malaria Vaccine Implementation Program (MVIP), coordinated by the WHO and completed at the end of 2023, found that immunization reduced mortality by only 13%. To further reduce malaria death, development of a more effective malaria vaccine is a high priority. Three major malaria vaccine targets being considered are the level of sporozoite liver infection, merozoite red blood cell (RBC) infection, and mosquito midgut infection. These targets involve specific ligand-receptor interactions. However, current malaria vaccine candidates that target two major parasite population bottlenecks, liver infection and mosquito midgut infection, do not focus on such parasite ligands. Here we evaluate the potential of newly identified parasite ligands as novel malaria vaccine antigens.

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A Comparison Between Recombinant Listeria GAPDH Proteins and GAPDH Encoding mRNA Conjugated to Lipids as Cross-Reactive Vaccines for Listeria, Mycobacterium, and Streptococcus

et al. 2021

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Cross-reactive vaccines recognize common molecular patterns in pathogens and are able to confer broad spectrum protection against different infections. Antigens common to pathogenic bacteria that induce broad immune responses, such as the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of the genera Listeria, Mycobacterium, or Streptococcus, whose sequences present more than 95% homology at the N-terminal GAPDH1−22 peptide, are putative candidates for universal vaccines. Here, we explore vaccine formulations based on dendritic cells (DC) loaded with two molecular forms of Listeria monocytogenes GAPDH (LM-GAPDH), such as mRNA carriers or recombinant proteins, and compare them with the same molecular forms of three other antigens used in experimental vaccines, listeriolysin O of Listeria monocytogeness, Ag85A of Mycobacterium marinum, and pneumolysin of Streptococcus pneumoniae. DC loaded with LM-GAPDH recombinant proteins proved to be the safest and most immunogenic vaccine vectors, followed by mRNA encoding LM-GAPDH conjugated to lipid carriers. In addition, macrophages lacked sufficient safety as vaccines for all LM-GAPDH molecular forms. The ability of DC loaded with LM-GAPDH recombinant proteins to induce non-specific DC activation explains their adjuvant potency and their capacity to trigger strong CD4+ and CD8+ T cell responses explains their high immunogenicity. Moreover, their capacity to confer protection in vaccinated mice against challenges with L. monocytogenes, M. marinum, or S. pneumoniae validated their efficiency as cross-reactive vaccines. Cross-protection appears to involve the induction of high percentages of GAPDH1−22 specific CD4+ and CD8+ T cells stained for intracellular IFN-γ, and significant levels of peptide-specific antibodies in vaccinated mice. We concluded that DC vaccines loaded with L. monocytogenes GAPDH recombinant proteins are cross-reactive vaccines that seem to be valuable tools in adult vaccination against Listeria, Mycobacterium, and Streptococcus taxonomic groups.

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

Abstract: 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.

Cited by 6 publications

References 31 publications

Glyceraldehyde-3-phosphate Dehydrogenase Common Peptides of Listeria monocytogenes, Mycobacterium marinum and Streptococcus pneumoniae as Universal Vaccines

Glyceraldehyde-3-phosphate Dehydrogenase Common Peptides of Listeria monocytogenes, Mycobacterium marinum and Streptococcus pneumoniae as Universal Vaccines

Targeting <em>Plasmodium </em>Population Bottlenecks with Parasite Ligands as Vaccine Antigens

A Comparison Between Recombinant Listeria GAPDH Proteins and GAPDH Encoding mRNA Conjugated to Lipids as Cross-Reactive Vaccines for Listeria, Mycobacterium, and Streptococcus

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