THE POTENTIAL USEFULNESS OF THE VIRAL CAPSID SURFACE PROTEINS (VP1, VP2, VP3 & VP4) FOR VACCINATION AGAINST COMMON COLD

AHMED SUBEH ALSHRARI
medical microbiology and parasitology, Universiti Putra Malaysia
September, 2015
 

Abstract

Rhinoviruses (RVs) represent the most important etiological agents of the common cold and it is 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 was carried out with the aim to develop a pan-serotypic vaccine that is capable of inducing the production of cross-reactive antibodies that cover all or most of the RV serotypes.

Firstly, a 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. On the other hand, 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.


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. Moreover, the specific immunoglobulin G (IgG) response to the peptides given in combination exhibited greater reactivity. Interestingly, the anti-peptide antibodies obtained exhibited a cross-neutralizing activity for different RV strains in vitro. In addition, the induced antibodies against recombinant proteins also reacted successfully with relevant proteins and with whole virus particle (HRV-74) and other variant strains, as shown by ELISA. They also showed strong cross-neutralizing ability against various variants of RVs.

The findings have indicated that the peptides corresponding to the conserved region of the RV capsid proteins are potent immunogenic and suggest that their combination is crucial for extending the cross-protection against variant RVs.