An immunoinformatics approach to epitope-based vaccine design against PspA in Streptococcus pneumoniae

Abstract

Background Streptococcus pneumoniae (SPN) is the agent responsible for causing respiratory diseases, including pneumonia, which causes severe health hazards and child deaths globally. Antibiotics are used to treat SPN as a first-line treatment, but nowadays, SPN is showing resistance to several antibiotics. A vaccine can overcome this global problem by preventing this deadly pathogen. The conventional methods of wet-laboratory vaccine design and development are an intense, lengthy, and costly procedure. In contrast, epitope-based in silico vaccine designing can save time, money, and energy. In this study, pneumococcal surface protein A (PspA), one of the major virulence factors of SPN, is used to design a multi-epitope vaccine. Methods For designing the vaccine, the sequence of PspA was retrieved, and then, phylogenetic analysis was performed. Several CTL epitopes, HTL epitopes, and LBL epitopes of PspA were all predicted by using several bioinformatics tools. After checking the antigenicity, allergenicity, and toxicity scores, the best epitopes were selected for the vaccine construction, and then, physicochemical and immunological properties were analyzed. Subsequently, vaccine 3D structure prediction, refinement, and validation were performed. Molecular docking, molecular dynamic simulation, and immune simulation were performed to ensure the binding between HLA and TLR4. Finally, codon adaptation and in silico cloning were performed to transfer into a suitable vector. Results The constructed multi-epitope vaccine showed a strong binding affinity with the receptor molecule TLR4. Analysis of molecular dynamic simulation, C-immune simulation, codon adaptation, and in silico cloning validated that our designed vaccine is a suitable candidate against SPN. Conclusion The in silico analysis has proven the vaccine as an alternative medication to combat against S. pneumoniae. The designated vaccine can be further tested in the wet lab, and a novel vaccine can be developed.

Multiepitope-based vaccine design against DiiA inStreptococcus pneumoniae, An immunoinformatics approach

“…Streptococcus pneumoniae (SPN), commonly known as pneumococcus, is a significant causative agent of community-acquired pneumonia, leading to a substantial number of deaths worldwide (Mazumder, Shahab et al 2023). A variety of infections brought on by this bacterium are referred to as pneumococcal diseases, which can have serious effects on global health (Brooks and Mias 2018).…”

“…Infected people have a nasopharyngeal infection that is initially asymptomatic until SPN establishes itself as a commensal flora in the upper respiratory tract (URT ) (Varghese, Jayaraman et al 2017) (Bittaye and Cash 2015). This gram-positive bacterium exhibits an elongated, round shape, is alpha-hemolytic, and possesses a capsule, while being non-motile and non-spore-forming (Mazumder, Shahab et al 2023). Beyond pneumonia, pneumococcal infections can result in various other serious health conditions, including bronchitis, brain abscess, otitis media, septicemia, meningitis, osteomyelitis, cellulitis, pericarditis, endocarditis, conjunctivitis, peritonitis, and acute sinusitis (Mitchell and Mitchell 2010, Brooks and Mias 2018, Mazumder, Shahab et al 2023).…”

“…This gram-positive bacterium exhibits an elongated, round shape, is alpha-hemolytic, and possesses a capsule, while being non-motile and non-spore-forming (Mazumder, Shahab et al 2023). Beyond pneumonia, pneumococcal infections can result in various other serious health conditions, including bronchitis, brain abscess, otitis media, septicemia, meningitis, osteomyelitis, cellulitis, pericarditis, endocarditis, conjunctivitis, peritonitis, and acute sinusitis (Mitchell and Mitchell 2010, Brooks and Mias 2018, Mazumder, Shahab et al 2023). By interfering with immune responses and producing harmful toxins, these pathogens disrupt the normal functioning of the human body.…”

“…Age plays a crucial role in the risk of developing pneumococcal pneumonia, with a significantly higher incidence observed in children under 2 years of age and adults over 65 years of age compared to adolescents (Ortqvist, Hedlund et al 2005). The impact of SPN infections is particularly severe among vulnerable populations, as evidenced by the substantial number of deaths, approximately 335,000, attributed to pneumococcal diseases in children in 2015 (Mazumder, Shahab et al 2023). Notably, regions such as South Asia and South Africa have experienced notable mortality rates, emphasizing the global burden of pneumococcal infections (Kumar, Arora et al 2016, von Mollendorf, Tempia et al 2017).…”

“…Many in-silico studies evaluated these virulence proteins as vaccine candidates for epitope-based vaccine design against SPN (Mazumder, Shahab et al 2023). SPN expresses several virulence factors, such as Polysaccharide capsule, the pore□forming toxin, pneumolysin (PLY), LPXTG motif-anchored surface proteins containing hyaluronidase, neuraminidase, and serine protease PrtA, pili, choline-binding proteins (CBPs),, pneumococcal surface proteins (PspA and PspC), pneumococcal histidine triad (Pht) proteins (PhtD and PhtE), and the lipoprotein components of iron uptake ATP-binding cassette (ABC) transporters (PiuA, PiaA, and PsaA) (Subramanian, Henriques-Normark et al 2019, Mazumder, Shahab et al 2023).…”