NDLI: Designing and comparative analysis of anti-oxidant and heat shock proteins based multi-epitopic filarial vaccines

Content Provider	Springer Nature : BioMed Central
Author	Kumar, Sunil Mishra, Ayushi Kumar, Vipin Singh, Tripti Singh, Amit Kumar Singh, Anchal
Abstract	Background Lymphatic Filariasis (LF) is a neglected tropical disease affecting more than 882 million people in 44 countries of the world. A multi-epitope prophylactic/therapeutic vaccination targeting filarial defense proteins would be invaluable to achieve the current LF elimination goal. Method Two groups of proteins, namely Anti-oxidant (AO) and Heat shock proteins (HSPs), have been implicated in the effective survival of the filarial parasites in their hosts. Several B-cell, CTL, and T-helper epitopes were predicted from the three anti-oxidant proteins GST, GPx, and SOD. Likewise, epitopes were also predicted for HSP110, HSP90, and HSP70. Among the predicted epitopes, screening was applied to include only non-allergenic, non-toxic epitopes to construct two MEVs, PVAO and PVHSP. The epitopes for each group of proteins were connected to each other by the inclusion of suitable linkers and an adjuvant. The 3D models for PVAO and PVHSP were predicted, and validated, followed by prediction of physicochemical properties using bioinformatics tools. The binding free energy of PVAO and PVHSP with Toll like Receptors (TLR) TLR1/2, TLR4, TLR5, TLR6, and TLR9 was calculated with HawkDock. The immunogenicity of both the MEVs were assessed by Immune simulation after which codon adaptation and in-silico cloning were carried out. Results Conservation of the selected AOs and HSPs in other parasitic nematode species suggested that both the generated chimera could be helpful in cross-protection too. The 3D models of both MEVs contained more than 97% residues in allowed regions, as predicted by PROCHECK server. High MMGBSA and docking scores were obtained between MEVs and TLR4, TLR1/2, TLR6, and TLR9. Molecular dynamics simulation confirmed the stability of candidate vaccines in dynamic conditions present in the biological systems. The in-silico immune simulation indicated significantly high levels of IgG1, T-helper, T-cytotoxic cells, INF-γ, and IL-2 responses following immunization with PVAO and PVHSP. Conclusion The immunoinformatics approaches used in this study confirmed that, the designed vaccines are capable of eliciting sustained immunity against LF, however, additional in-vivo studies would be required to confirm their efficacy. Furthermore, by employing multi-epitope structures and constructing two different cocktail vaccines for LF, this study can form an important milestone in the development of future LF vaccine/s.
Related Links	https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-024-10272-9.pdf
Ending Page	25
Page Count	25
Starting Page	1
File Format	HTM / HTML
ISSN	14712334
DOI	10.1186/s12879-024-10272-9
Journal	BMC Infectious Diseases
Issue Number	1
Volume Number	24
Language	English
Publisher	BioMed Central
Publisher Date	2024-12-18
Access Restriction	Open
Subject Keyword	Infectious Diseases Parasitology Medical Microbiology Tropical Medicine Internal Medicine Filarial anti-oxidant proteins Filarial heat shock proteins Filarial cocktail vaccine Multi-epitope vaccines
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases
Journal Impact Factor	3.4/2023
5-Year Journal Impact Factor	3.3/2023

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