Generating Neutralizing Antibody responses using Recombinant Infectious Rhinovirus

Abstract

Abstract Human Rhinovirus (RV), a leading causative agent for common colds and the subsequent development of pneumonia, can exacerbate both asthma and chronic obstructive pulmonary disease (COPD). There is no vaccine against RV yet. As previous studies demonstrated that RV-neutralizing antibodies (nAb) correlates with protection, eliciting robust nAb responses might be a key factor for ideal RV vaccine development. Five neutralizing immunogenic (NIm) sites were identified. NIm-IA, IB, and IV are located on VP1, while NIm-II and III are located on VP2 and VP3, respectively. Since the capsid proteins (VP1, 2, 3 and 4) seem to be immunogenic, we hypothesize that a chimeric virus expressing the capsid proteins is sufficient to elicit nAb responses. The HRV-A76 insert expressing the four capsid proteins and 2A protein was cloned into a bacterial artificial chromosome (BAC) harboring cDNA expressing the full-length genome of HRV-A33. Utilizing reverse genetics, a capsid-chimeric recombinant RV strain, BAC HRV33cap76, was generated using the four capsid proteins and 2A protein from HRV-A76, and the remaining part of the genome from HRV-A33. Following RNA transfection and recovery, we found that the titer of BAC HRV33cap76 was similar to biological HRV33 or HRV76. We next immunized BALB/c mice intramuscularly with inactivated BAC HRV33cap76 mixed with alum adjuvant to determine its immunogenicity. The BAC HRV33cap76 immunization resulted in nAb against only HRV-A76. Our findings demonstrated that the capsid proteins are responsible for the generation of nAb against RV. As a capsid-chimeric recombinant RV was capable of eliciting robust nAb, it could be a novel vaccine platform to generate highly effective and safe vaccine for preventing RV infection.