Abstract
Rhinoviruses (RVs) are the main cause of the common cold worldwide. To date, more than 160 types of the virus have been recognized, categorized into three major species - A, B, and C. There are currently no approved vaccines available to prevent infection with RVs. To elicit antibodies against conserved regions located on capsid proteins of RV A viruses, mice were sequentially vaccinated with DNA plasmids encoding capsid proteins of different RV A types. After a final boost with whole virus, antibody-expressing hybridomas were generated. After isotyping, 11 monoclonal antibodies (mAbs) expressing an IgG subtype Fc-domain were selected for further expansion and purification. Three mAbs showed cross-reactivity against multiple strains of RV A viruses by ELISA, including strains A1A, A1B, A15, A16 and A49. Other mAbs had strain-specific binding patterns, with the majority of mAbs showing reactivity to RV-A15, the strain used for the final vaccination. We found that the RV-A15-specific mAbs, but not the cross-reactive mAbs, had neutralizing activity against RV-A15. An antibody dependent cellular phagocytosis (ADCP) assay revealed substantial ADCP activity for one of the cross-reactive mAbs. Epitope mapping of the neutralizing mAbs via escape mutant virus generation revealed a shared binding epitope on VP1 of RV-A15 for several neutralizing mAbs. The epitope of the ADCP-active, non-neutralizing mAb was determined by microarray analysis of peptides generated from the VP1 capsid protein. VP1-specific, cross-reactive antibodies, especially those with ADCP activity, could contribute to protection against RV infections.
Highlights
Rhinoviruses (RVs) are the main cause of the common cold worldwide
We utilized a sequential DNA vaccination approach expressing the capsid proteins of heterologous types of RV, followed by a final whole virus boost with RV-A15 to elicit cross-reactive antibodies
Four of the neutralizing RV-A15-specific monoclonal antibodies (mAbs) were isolated from the same mouse and likely were clonally related, based on their binding of a shared epitope on VP1
Summary
Rhinoviruses (RVs) are the main cause of the common cold worldwide. To date, more than 160 types of the virus have been recognized, categorized into three major species - A, B, and C. Neutralizing antibodies elicited by infection can reduce viral replication, only limited cross-protection against heterologous strains is provided because of the large antigenic diversity of RVs17. Previous attempts to establish cross-type protection using vaccines containing multiple conserved regions of the virus had some success in eliciting neutralizing responses[18,19,20,21]. Despite these early successes, whether or not viable cross-reactive targets for cross-protective vaccines exist remains an open question. We identified three cross-reactive monoclonal antibodies (mAbs) While these mAbs did not exhibit neutralizing activity, one mAb interestingly showed a high level of activity in an antibody-dependent cellular phagocytosis (ADCP) assay
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