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Vol. 25. Issue 3.
Pages 385-402 (July - September 2024)
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Vol. 25. Issue 3.
Pages 385-402 (July - September 2024)
Review article
Immunoinformatics strategy for designing a multi-epitope chimeric vaccine to combat Neisseria gonorrhoeae
Estrategia inmunoinformática para el diseño de una vacuna multiepitópica quimérica para combatir Neisseria gonorrhoeae
P. Priyamvadaa,c,1, Rayapadi G. Swethaa,b,1, Rupsha Dasguptaa,b, Anand Anbarasua,b, Sudha Ramaiaha,c,
Corresponding author
sudhaanand@vit.ac.in

Corresponding author at: SBST, VIT, Vellore 632014, India.
a Medical and Biological Computing Laboratory, School of Biosciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore 632014, India
b Department of Biotechnology, SBST, VIT, Vellore 632014, India
c Department of Biosciences, SBST, VIT, Vellore 632014, India
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Tables (8)
Table 1. Antigenicity and solubility of 4 finalized OMPs (membrane protein_1, biopolymer transporter, membrane protein_2, outer membrane protein assembly factor BamA).
Table 2. The immunogenicity, antigenicity, and toxicity of 21 MHC class-I T-cell epitopes. The epitopes in green are the finalized MHC class-I T-cell epitopes.
Table 3. The immunogenicity, antigenicity, and toxicity of 35 MHC class-II T-cell epitopes. The epitopes in green are the finalized MHC class-II T-cell epitopes.
Table 4. Combined results of MHC class-I T-cell, MHC class-II T-cell and B cell epitope prediction in 3 filtered proteins.
Table 5. Allergenicity, antigenicity, solubility, and physio-chemical properties of predicted 20 vaccine constructs. The highlighted vaccine constructs were considered as potent vaccine candidates.
Table 6. Structural quality comparison of the modeled vaccine constructs.
Table 7. The relative binding energies of the docked complexes obtained from ClusPro.
Table 8. Total binding free energy including van der waal, electrostatic energy, Generalized Born contribution and surface area interactions of different target molecules interactions with V13.
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Abstract
Introduction

The increasing prevalence of Neisseria gonorrhoeae has become a significant global concern. Consequently, it is of utmost importance to explore prophylactic approaches to combat the anti-microbial resistance in N. gonorrhoeae.

Objective

The present study aims to design a multi-epitopic vaccine construct using immunoinformatics and pan-genomic methodology.

Methods

The initial phase involves retrieving and re-annotating the 133 complete genome sets of N. gonorrhoeae. Subsequently, a pan-genome analysis was conducted to identify the core genes, followed by gene mapping. Non-homologous outer-membrane proteins were filtered out and analyzed using various epitope prediction algorithms targeting major histocompatibility complex (MHC-I, MHC-II), and B cells. The optimal epitopes were selected based on immunogenicity, antigenicity, toxicity, and solubility. Then, the vaccine constructs were designed using different combinations of linkers, Histidine (His) tags, adjuvants, and the finalized epitopes.

Results

The vaccine construct, V13 was screened as the most suitable candidate based on its physiochemical and antigenicity properties. Computational techniques assessed the efficacy of V13 against different immune receptors supported by immune simulation, indicating its safety for inducing immune responses against N. gonorrhoeae.

Conclusion

The chimeric multi-epitopic vaccine V13 construct can potentially trigger a diverse array of protective immune responses and serve as a promising starting point for future experimental investigations.

Keywords:
Resistance
Neisseria gonorrhoeae
Vaccine
Pan-genome
Reverse vaccinology
Resumen
Introducción

La prevalencia creciente de Neisseria gonorrhoeae se ha convertido en una preocupación global significativa. Por tanto, es de máxima importancia explorar los enfoques profilácticos para combatir la resistencia antimicrobiana de N. gonorrhoeae.

Objetivo

El objetivo del presente estudio es diseñar un constructo de vacuna multiepitópica utilizando inmunoinformática y metodología pangenómica.

Métodos

La fase inicial implica la extracción y reanotación de los 133 conjuntos de genomas completos de N. gonorrhoeae. A continuación se realizó un análisis pangenómico para identificar los genes principales, seguido de un mapeo genético. Se filtraron y analizaron las proteínas de la membrana externa no homólogas utilizando diversos algoritmos de predicción de epítopos dirigidos a los complejos mayores de histocompatibilidad CMH-I, CMH-II y a las células B. Se seleccionaron los epítopos óptimos sobre la base de inmunogenicidad, antigenicidad, toxicidad y solubilidad. Seguidamente, se diseñaron los constructos de la vacuna utilizando diferentes combinaciones de enlazadores, etiquetas de Histidina (His), adyuvantes y los epítopos finalizados.

Resultados

Se cribó el constructo de la vacuna V13 como el candidato más idóneo, sobre la base de sus propiedades fisioquímicas y de antigenicidad. Las técnicas informáticas evaluaron la eficacia de V13 frente a diferentes receptores inmunes con soporte de simulación inmunológica, indicando su seguridad para la inducción de respuestas inmunológicas frente a N. gonorrhoeae.

Conclusión

El constructo quimérico V13 de la vacuna multiepitópica puede desencadenar potencialmente un conjunto diverso de respuestas inmunológicas protectoras y servir como punto de partida prometedor para investigaciones experimentales futuras.

Palabras clave:
Resistencia
Neisseria gonorrhoeae
Vacuna
Pangenoma
Vacunología inversa

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