Document Type Doctoral Thesis Author Weyer, Jacqueline email@example.com URN etd-09222006-123129 Document Title Immune responses against recombinant poxvirus vaccines that express full-length lyssavirus glycoprotein genes Degree PhD (MIcrobiology) Department Microbiology and Plant Pathology Supervisor
Advisor Name Title Prof L H Nel Keywords
- rabies virus
- rabies in animals-vaccination
- Ir genes
- rabies vaccines
- Immune response
- recombinant poxviruses
Date 2006-05-02 Availability unrestricted Abstract
A proven approach is mass oral vaccination of target animals, such as dogs, which indirectly infers protection to susceptible hosts, including man. Currently available vaccines present several disadvantages of use though, including issues of safety or doubtful stability. Safer but effective alternative vaccines that could be used in oral baits would be valuable. Here the use of two candidate host restricted poxvirus vaccine vectors were explored, particularly also in regard to oral innocuity. The construction, convenient isolation and use of a recombinant Lumpy skin disease virus (Neethling strain) expressing rabies virus glycoprotein in a mouse model were investigated. In addition, a recombinant Modified Vaccinia virus Ankara expressing rabies virus glycoprotein was prepared and tested as a vaccine in mice, dogs and raccoons. In both cases it was clear that the severe attenuation of these viruses did affect the efficacy of the recombinant vaccines in the non-permissive hosts. With the recombinant MVA a clear dosage effect could be shown, and equivalent humoral responses could only be attained at much higher titers of vaccine virus as with replication competent counterparts.
Secondly, the cross-protection of rabies vaccines across the spectrum of lyssaviruses was addressed. Lyssaviruses can be divided into two groups based on sequence analysis and pathogenesis. Viruses belonging to the so-called phylogroup II, are the Mokola, Lagos and West Caucasian Bat viruses. Classic rabies biologics fail to fully protect against the viruses attributed to a lack of cross-neutralization.
Here, cross-protection and cross-reactive immune responses induced by recombinant vaccinia viruses expressing rabies, Mokola or West Caucasian Bat virus glycoproteins, in single or dual combinations, were investigated. As expected, there was a lack of cross-protection of rabies and Mokola glycoprotein vaccines. There was also a clear lack of cross-protection of West Caucasian Bat virus glycoprotein vaccine and rabies and Mokola viruses. The dual antigen expressing vaccines did not appear to offer any additional protective effect in the tested model. The Mokola virus glycoprotein vaccines induced neutralizing antibody responses that significantly cross-neutralized Lagos Bat virus.
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28.8 Modem 56K Modem ISDN (64 Kb) ISDN (128 Kb) Higher-speed Access 00front.pdf 190.74 Kb 00:00:52 00:00:27 00:00:23 00:00:11 00:00:01 01chapter1.pdf 896.15 Kb 00:04:08 00:02:08 00:01:52 00:00:56 00:00:04 02chapter2.pdf 901.35 Kb 00:04:10 00:02:08 00:01:52 00:00:56 00:00:04 03chapter3.pdf 436.69 Kb 00:02:01 00:01:02 00:00:54 00:00:27 00:00:02 04chapter4.pdf 431.14 Kb 00:01:59 00:01:01 00:00:53 00:00:26 00:00:02 05chapter5.pdf 692.72 Kb 00:03:12 00:01:38 00:01:26 00:00:43 00:00:03 06chapter6.pdf 686.15 Kb 00:03:10 00:01:38 00:01:25 00:00:42 00:00:03 07chapter7.pdf 734.35 Kb 00:03:23 00:01:44 00:01:31 00:00:45 00:00:03 07chapter7.pdf 734.35 Kb 00:03:23 00:01:44 00:01:31 00:00:45 00:00:03 08chapter8.pdf 171.43 Kb 00:00:47 00:00:24 00:00:21 00:00:10 < 00:00:01 09References.pdf 171.43 Kb 00:00:47 00:00:24 00:00:21 00:00:10 < 00:00:01