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

Autor: Kumar S; Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, UP, 221005, India., Mishra A; Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, UP, 221005, India., Kumar V; Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, UP, 221005, India., Singh T; Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, UP, 221005, India., Singh AK; Department of Medical Health and Family Welfare, Malaria and Vector Borne Disease, Filaria Control Unit Varanasi, Varanasi, UP, 221005, India., Singh A; Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, UP, 221005, India. anchalsinghbhu@yahoo.com.
Jazyk: angličtina
Zdroj: BMC infectious diseases [BMC Infect Dis] 2024 Dec 18; Vol. 24 (1), pp. 1436. Date of Electronic Publication: 2024 Dec 18.
DOI: 10.1186/s12879-024-10272-9
Abstrakt: 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, PV AO and PV HSP . 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 PV AO and PV HSP were predicted, and validated, followed by prediction of physicochemical properties using bioinformatics tools. The binding free energy of PV AO and PV HSP 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 IgG 1 , T-helper, T-cytotoxic cells, INF-γ, and IL-2 responses following immunization with PV AO and PV HSP .
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.
Competing Interests: Declarations. Ethical approval: This study does not involve any human or animal subject. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje