Keywords
Virus-like Particles (VLPs); RSV; RSV VLPs; Prefusion F RSV VLPs
Abstract
Respiratory Syncytial Virus (RSV) infection is of public health concern worldwide. Globally, it is a common cause of bronchiolitis and pneumonia in childhood, outbreaks occurs every year depending on the locale. Worldwide, it is estimated that 30 million Lower Respiratory Tract Infections (LRI), 3 million hospitalization and 160,000 deaths occur annually. It also causes morbidity/mortality in the elderly/at risk adults. In spite of concentrated efforts of many over more than five decades, vaccine or therapy for this virus has remained elusive. Many conventional and newer vaccine strategies have been evaluated but none have been licensed to date. We are exploring mammalian cell-derived Virus-like Particles (VLPs) composed of the two surface glycoproteins G and prefusion F (RSV fVLPs) and M as vaccine. In prefusion F there is a neutralizing epitope at site zero that induces significantly higher Neutralizing Antibody (NtAb) titers. In preliminary studies, we have shown by Electron Microscopy (EM) that our fVLPs are functional and immunoreactive. We have done western blot with two conformation dependent antibodies AM14, and D25, and Motavizumab which is conformation independent. We have shown also that MPLA-adjuvanted fVLPs induced 8.2Log2±1.13 NtAb titers. With regular F (instead of prefusion F) lower NtAb titers are seen in cotton rats and in mice. On challenge lung virus titers in the homogenate was almost clear.
Citation
Walpita P and Johns LM. Respiratory Syncytial Virus-like Particles Consisting of M, G and Prefusion F. SM Trop Med J. 2016; 1(2): 1008.