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.
Highlights
Dendritic cells (DC) are efficient experimental vaccine vectors as they can stimulate CD8+ and CD4+ T cells and induce Th1 cytokine profiles, relevant features of efficient vaccines for infectious diseases
We explore the possibility that dendritic cells (DC) vaccines loaded with GAPDH1–22 peptides of Listeria monocytogenes (GAPDH-Listeria monocytogenes: GAPDH1–22 (L1)), Mycobacterium marinum (GAPDH-M1) or Streptococcus pneumoniae (GADPH-Streptococcus pneumoniae GAPDH1–22 (S1)) acted as universal vaccines against these pathogens
DC vaccines loaded with LLO91–99 showed no significant frequencies of CD8+ T cells specific for any GAPDH peptide, indicating the high specificity of the assay. These results strongly suggested that cross-reactive DC vaccines loaded with GAPDH-L1, GAPDH-M1 or GAPDH-S1 peptides provide two types of T cell responses, high-specific CD8+ T cells for the vaccinated epitope, and broader CD8+ T cell responses to GAPDH epitopes sharing more than 98% sequence homology
Summary
Dendritic cells (DC) are efficient experimental vaccine vectors as they can stimulate CD8+ and CD4+ T cells and induce Th1 cytokine profiles, relevant features of efficient vaccines for infectious diseases. In this regard, DC vaccines have been proposed against different viral and bacterial infections such as hepatitis C virus (HCV), human immunodeficiency virus (HIV), type 2 coronavirus (SARS-CoV2), Streptococcus pneumonia, Chlamydia trachomatis, Mycobacterium tuberculosis and Listeria monocytogenes [1,2,3,4,5,6,7,8,9,10]. We explore the possibility that DC vaccines loaded with GAPDH1–22 peptides of Listeria monocytogenes (GAPDH-L1), Mycobacterium marinum (GAPDH-M1) or Streptococcus pneumoniae (GADPH-S1) acted as universal vaccines against these pathogens
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.