Author : Anzhong Li (Virologist)
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (141 download)
Book Synopsis Non-segmented Negative-sense RNA Viruses as Vectors for Developing Vaccine Candidates Against Zika Virus Infection by : Anzhong Li (Virologist)
Download or read book Non-segmented Negative-sense RNA Viruses as Vectors for Developing Vaccine Candidates Against Zika Virus Infection written by Anzhong Li (Virologist) and published by . This book was released on 2020 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Zika virus (ZIKV) is a member of the family Flaviviridae which includes many other important mosquito-borne viruses such as dengue virus (DENV), West Nile virus (WNV), and yellow fever virus (YFV). Since it was discovered in 1947, sporadic outbreaks of ZIKV have been reported in Africa and Asia. Historically people infected with ZIKV often have no or mild symptoms. However, in 2015 a ZIKV pandemic began in South America, Central America, the Caribbean, and the USA, suddenly becoming a global public health issue. Importantly, ZIKV from these recent outbreaks can cause Congenital Zika Syndrome (including microcephaly), Guillain-Barre syndrome, and other severe neurological disorders. Thus, a safe and efficacious vaccine is urgently needed for ZIKV. Similar to other flaviviruses, the ZIKV genome encodes a single polyprotein that is cleaved into three structural proteins (capsid, C; premembrane, prM, and envelope, E) and seven nonstructural proteins. The E protein mediates cellular attachment and membrane fusion, and is the target for most neutralizing antibodies. Flavivirus prM protein typically associates with E to form heterodimers and is important for proper folding of E. Therefore, prM and E proteins have been the primary targets for subunit and recombinant ZIKV vaccine studies. Meanwhile, the nonstructural protein NS1 of several flaviviruses has been shown to confer some protection against flavivirus infection in animal models in the absence of detectable neutralizing antibody. Whether immunization with the ZIKV NS1 protein has certain protective capabilities is unclear. The goal of my research is to develop vesicular stomatitis virus (VSV) and measles virus (MeV)-based vaccine candidates for ZIKV. Both VSV and MeV are non-segmented negative-sense (NNS) RNA viruses. VSV is an animal virus and has been shown to be an excellent vaccine vector because of its high genetic stability and expression efficiency and no pre-existing immunity in the human population. In 2019, a VSV-based Ebola virus vaccine was approved by FDA for human uses. MeV is another excellent vector to deliver vaccines for human pathogens primarily because of its high safety and efficacy even in the presence of pre-existing anti-MeV vector immunity. Several MeV-based vaccine candidates are highly efficacious in human clinical trials. In Chapter 2, I developed a methyltransferase (MTase)-defective recombinant VSV (mtdVSV)-based ZIKV vaccine platform. The full-length E, E truncation mutants, prM-E, NS1, and prM-E-NS1 of ZIKV were inserted individually into a VSV vector that carrying an MTase mutation in the large polymerase protein.