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

Abstract

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.

Testing a vaccine candidate against Hepatitis C virus designed by combinatorial optimization

“…Negative controls encompassed empty DC and DC loaded with PCONT, while positive controls consisted of DC vaccines loaded with a viral SARS-CoV2 peptide (CoVPSA) or a bacterial Listeria peptide (GAPDH1-22), both known for their effective vaccine performance 27 , 28 . Analysis of DTH responses (Fig.…”

“…Lastly, the effectiveness of a vaccine is commonly associated with the generation of specific immune responses, either T cell responses, both CD4 + and CD8 + peptide-specific, or antibodies against the vaccine’s antigen. In this context, we first evaluated the frequencies of HCV peptide-specific CD4 + and CD8 + producing IFN-γ, as a measure of specific immunogenicity associated with protective DC vaccines 27 , 28 . DC vaccines loaded with HCV peptides that showed the highest T cell percentages, DC-DYP and DC-STG (see Fig.…”

Streptococcus pneumoniae extracellular vesicles aggravate alveolar epithelial barrier disruption via autophagic degradation of OCLN (occludin)

“…However, the influence of S. pneumoniae ATP synthase on host autophagy and subsequent effects on host response remains unexplored. Additionally, another pEVs-associated protein Gap (Glyceraldehyde-3-phosphate dehydrogenase, GAPDH) is a common virulence factor among pathogenic bacteria of the genera Listeria , Mycobacterium , and Streptococcus [ 86 ]. It serves as a key enzyme in metabolism and plays an important role in cell autophagy [ 87 ].…”

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

“…Immunization with recombinant GAPDH of Streptococcus dysgalactiae, a bacterial pathogen causing intramammary infections in dairy bovines, improved the survival rates and decreased the bacterial burdens in the mammary glands in immunized mice [24]. Conserved GAPDH peptides among multiple pathogens have been explored for a universal vaccine antigen that target Listeria monocytogenes, Mycobacterium marinum and Streptococcus pneumoniae [25,26]. On the other hand, predicted GAPDH B-cell epitopes and pyruvate dehydrogenase E1 subunit alpha in Streptococcus iniae, a bacterial flounder pathogen, were fused for a multiple epitope vaccine antigen, which increased survival rate in immunized animals compared to single antigen immunized animals [27].…”