Prophylactic antibody treatment and intramuscular immunization reduce infectious human rhinovirus 16 load in the lower respiratory tract of challenged cotton rats

Jorge C.G Blanco,Susan Core,Lioubov M Pletneva,Thomas H March,Marina S Boukhvalova,Adriana E Kajon

doi:10.1016/j.trivac.2014.02.003

Abstract

Human rhinoviruses (HRV) represent the single most important etiological agents of the common cold and are the most frequent cause of acute respiratory infections in humans. Currently the performance of available animal models for immunization studies using HRV challenge is very limited. The cotton rat (Sigmodon hispidus) is a well-recognized model for the study of human respiratory viral infections. In this work we show that, without requiring any genetic modification of either the host or the virus, intranasal infection of cotton rats with HRV16 resulted in measurable isolation of infective virus, lower respiratory tract pathology, mucus production, and expression of interferon-activated genes. Intramuscular immunization with live HRV16 generated robust protective immunity that correlated with high serum levels of neutralizing antibodies. In addition, cotton rats treated prophylactically with hyperimmune anti-HRV16 serum were protected against HRV16 intranasal challenge. Finally, protection by immunization was efficiently transferred from mothers to newborn animals resulting in a substantial reduction of infectious virus loads in the lung following intranasal challenge. Overall, our results demonstrate that the cotton rat provides valuable additional model development options for testing vaccines and prophylactic therapies against rhinovirus infection.

Highlights

Human rhinoviruses (HRV) represent the most important etiological agents of common colds and the most frequent cause of acute respiratory infections in humans [1,2,3]
We compared the viral load in the lung, between rats infected with the major group HRV16 and rats infected with the minor group HRV1B and found that the course of infection with the 2 viruses was very different (Fig. 1B)
Higher infectious virus titers were recovered from the lungs of animals infected with HRV16 than from animals infected with a similar dose of hRV1B, suggesting that the cotton rat is significantly more permissive to infection by HRV16

Summary

Introduction

Human rhinoviruses (HRV) represent the most important etiological agents of common colds and the most frequent cause of acute respiratory infections in humans [1,2,3]. The recent sequencing and analysis of all known HRV serotypes classified within species A and B and of genomic RNA corresponding to species rhinovirus C allowed a better understanding of evolutionary relations among viruses classified within the 3 species and of some of the structural implications of genetic variability in genes encoding capsid proteins [6,7]. Due to the occurrence of more than 100 HRV serotypes with extensive sequence variability in the antigenic sites and the lack of animal models to test the efficacy of approaches to prevent or treat infection in vivo, no rhinovirus vaccines are available for use in humans. The lack of animal models has limited the ability to conduct preclinical studies of antiviral compounds

Methods

Results

Conclusion