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The role of virus neutralisation in immunity to feline immunodeficiency virus infection

Samman, Ayman (2010) The role of virus neutralisation in immunity to feline immunodeficiency virus infection. PhD thesis, University of Glasgow.

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Abstract

Feline immunodeficiency virus (FIV) is an important veterinary pathogen with comparative significance because of its similarities to its human counterpart HIV. Since FIV is the only non-primate lentivirus which induces AIDS-like symptoms in its natural host, it serves as a valuable animal model for both prophylactic and therapeutic studies of HIV. It is accepted that the induction of neutralising antibodies (NAbs) is a key element in the control of lentiviral infection, since T-cell based vaccines alone failed to prevent infection in most experimental animal model systems. In this project a robust and reproducible in vitro neutralisation assay was developed and optimised, permitting the assessment of the NAb response in naturally infected cats and with the potential to evaluate candidate vaccines. It was demonstrated that, in general, primary FIV strains in the UK belong to subtype A, and therefore the development of a regional, subtype A-specific, FIV vaccine could be considered for use in the UK. The identification of a neutralisation resistant isolate of FIV led to the finding that a linear neutralisation determinant was located within the V5 region of Env and mutations in this region may lead to immune evasion in vivo. In addition, a second neutralisation determinant was identified in the C3/V4 region of Env. Finally, it was observed that a small proportion of naturally infected cats generated NAbs against FIV. Of these, only a very small proportion of the cats had antibodies with the potential to cross neutralise strains within the same subtype as the homologous isolate. Nonetheless, a plasma sample from a single cat was identified that neutralised all strains tested, including strains from different subtypes and geographical regions. It is likely that studies of the homologous isolate that induced the broad NAb response may be capable of inducing a similar broad response in vaccinated cats. Such a finding would have important implications for the design of potential novel lentiviral immunogens.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Feline Immunodeficiency Virus, FIV, neutralising antibodies, NAbs, virus neutralisation assay, VNA, N-linked glycosylation, PNGS, mutagenesis, luciferase, enhancement, aNAbs, bNAbs, HIV, phylogeny, UK, subtype A, neutralisation determinant, V3, C3-V4, V5, V1/V2 analogue, cat, Env, vaccine
Subjects: Q Science > QR Microbiology > QR180 Immunology
Q Science > QR Microbiology
R Medicine > RB Pathology
Q Science > QR Microbiology > QR355 Virology
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Supervisor's Name: Hosie, Prof. Margaret and Willett, Prof. Brian
Date of Award: 2010
Depositing User: Dr Ayman Samman
Unique ID: glathesis:2010-1554
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 02 Mar 2010
Last Modified: 10 Dec 2012 13:42
URI: http://theses.gla.ac.uk/id/eprint/1554

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