Reverse Vaccinology Approach for a Potential Rhinovirus Vaccine

Shuaibu Abdullahi Hudu,Babazhitsu Makun,Shuaibu Umar,Saadatu Haruna Shinkafi

doi:10.34172/ajcmi.2021.12

Shuaibu Abdullahi Hudu, Babazhitsu Makun + Show 2 more

Open Access

https://doi.org/10.34172/ajcmi.2021.12

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Abstract

Background: Rhinoviruses (RVs) represent the most important aetiological agents of the common cold and are responsible for about two-thirds of acute exacerbations of chronic bronchitis, asthma, and chronic obstructive pulmonary disease (COPD) in both children and adults. This study aimed to design a pan-serotypic vaccine capable of inducing cross-reactive antibodies against most of the RV by using a reverse Vaccinology approach. Methods: Bioinformatics analysis was carried out to characterise the capsid proteins (VP1, VP2, VP3, and VP4) of all known RV serotypes and to predict potential immune motifs. Conserved motifs consisting at least nine-mers common across all RV-A or B serotypes were selected and synthesized chemically. Four tagged full-length genes coding the capsid proteins of an ideal strain (HRV-74), VP1, VP2, VP3, and VP4 were constructed and cloned in vitro. Upon expression , the purified recombinant proteins were also administered subcutaneously to other groups of rabbits. The responses and cross-reactivity of the specific immunoglobulin M (IgM) and G (IgG) to the peptides, proteins, and whole viruses were measured. Results: The obtained anti-peptide antibodies exhibited a cross-neutralizing activity for different RV strains in vitro. Antibodies raised to the synthetic peptides exhibited cross-reactivity against the corresponding recombinant proteins and antigenically distinct RV strains coated on plates via ELISA assay. Conclusions: The study findings indicated that the peptides corresponding to the conserved region of the RV capsid proteins were potent immunogenic; moreover, the findings showed that their combination was crucial for extending the cross-protection against variant RVs.

Highlights

Rhinoviruses (RVs) represent the most important aetiological agents of the common cold and are responsible for about two-thirds of acute exacerbations of chronic bronchitis, asthma, and chronic obstructive pulmonary disease (COPD) in both children and adults
Further analysis showed that HRV-74 had the highest homology to consensus sequence (86%)
The consensus identity within RV-A group ranged from a low level of 64.8% (HRV-8) to a high level of 86% (HRV-74) with median identity of 77.27%

Summary

Introduction

Rhinoviruses (RVs) represent the most important aetiological agents of the common cold and are responsible for about two-thirds of acute exacerbations of chronic bronchitis, asthma, and chronic obstructive pulmonary disease (COPD) in both children and adults. This study aimed to design a pan-serotypic vaccine capable of inducing cross-reactive antibodies against most of the RV by using a reverse Vaccinology approach. Antibodies raised to the synthetic peptides exhibited cross-reactivity against the corresponding recombinant proteins and antigenically distinct RV strains coated on plates via ELISA assay. Conclusions: The study findings indicated that the peptides corresponding to the conserved region of the RV capsid proteins were potent immunogenic; the findings showed that their combination was crucial for extending the cross-protection against variant RVs. Keywords: Antibodies, Cross-protection, Reverse vaccinology, Rhinovirus, Vaccine. Rhinovirus (RV) was first isolated by Pelon et al and Price in 1956 [1] It is considered as the most important cause of common cold and is well recognised as causative agents for the self-limiting disease of the respiratory tract. It is almost impossible to avoid RV infection since millions of these viral particles are transmitted via exhalation during conversation, sneezing, coughing, and direct contact; this virus can remain infectious for a relatively long time [11]

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