LENTIVIRAL VECTORS

• Lenti- latent-slow• Retroviridae• Enveloped , spherical viruses with a genome size of

~ 8kb• Can replicate in the non dividing cells-making them

one of the most efficient gene delivery vector• Although transmission is generally via infectious

particles, lentiviruses are capable of infecting neighboring cells in direct contact with the host cells, without having to form extracellular particles.

INTRODUCTION

•Human Immunodeficiency Virus 1 and 2•Simian Immunodeficiency Virus•Feline Immunodeficiency Virus•Bovine immunodeficiency virus

•Equine infectious anemia virus•Caprine arthritis•Caprine encephalitis virus•Puma lentivirus

MEMBERS

HOW TO MAKE A VIRAL VECTOR FROM THE VIRUS?

LENTIVIRUS GENOME

PROCESS

THE STEPS INVOLVED

EXPERIMENTALLY

NO HELPER VIRUS- NO GOI!

THE PROBLEM-GENETIC RECOMBINATION!

SOLUTION

TYPE CARRIER TARGETLive attenuated virus SIVmac239 ( carries

deletion in nef gene)SIV (primates)

Inactivated whole virus vaccines

Chemical inactivation FIV (cats)

Subunit vaccines ISCOM (envelop and core protein) in addition to nef peptides

SIV (primates) - developed neutralizing Abs and MHC I restricted CTL responses against the virus

VLP based HBcAg and AbsAg are self aggregating proteins. Fusions of the V3 domain from HIV -1 to either the N- or C-terminal of HBcAg.

HIV-1 (induction of neutralizing antibodies)

VACCINES CURRENTLY AVAILABLE

TYPE CARRIER TARGETLive, recombinant, viral and bacterial carriers

VLP based Salmonella strains

Nucleic acid immunization

Viral-vector based HIV challenge produced neutralizing antibodies and specific CTL responses

• Lentiviruses have a high mutation rate due to low fidelity of the lentivirus reverse transcriptase and the absence of proofreading activity. This results in the constant generation of mutants that escape from surveillance either by antibodies or specific T -cells.

• Following integration of the proviral DNA into the host genome lentiviruses can remain in a quiescent state, invisible for the immune system. The initial site of infection is usually at the mucosae of the genital tracts or the intestine where the virus can replicate in the dendritic cells.

• To limit viral replication in this initial stage of infection the induction of an effective mucosal immune response will be necessary. Unfortunately most vaccine strategies pursued currently do not induce mucosal immune responses.

• Another problem in the immunologic control of lentivirus infection is that they destroy or interfere with the functioning of T helper cells which have a key role in the immune system.

SAFETY ISSUES

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