Journal Article

Protection against feline immunodeficiency virus using replication defective proviral DNA vaccines with feline interleukin-12 and -18

Hanlon, Linda, Harbour, David A, Macdonald, Julie, Golder, Matthew C, Mackay, Nancy A, Dunham, Stephen P, Jarrett, Oswald, Neil, James C, Flynn, J.Norman, Rigby, Mark A, Bruce, Jennifer, Cannon, Celia, Spibey, Norman

2002

Overview

A molecular clone of the Glasgow-8 isolate of FIV (FIV GL8) was rendered replication defective by an in-frame deletion in either reverse transcriptase (ΔRT) or integrase (ΔIN) genes for use as DNA vaccines. To test the ability of these multi-gene vaccines to protect against two feline immunodeficiency virus (FIV) isolates of differing virulence, cats were immunized using either DNA vaccine alone or co-administered with interleukin-12 (IL-12) and/or interleukin-18 (IL-18) cytokine DNA. Animals were challenged sequentially with FIV-Petaluma (FIV PET) an FIV isolate of relatively low virulence and subsequently with the more virulent FIV GL8. A proportion of vaccinates (5/18 ΔIN and 2/12 ΔRT) were protected against primary challenge with FIV PET. Five of the vaccinated-protected cats were re-challenged with FIV PET; four (all ΔIN) remained free of viraemia whilst all naive controls became viraemic. Following subsequent challenge with the more virulent FIV GL8 these four vaccinated-protected animals all became viraemic but showed lower proviral loads than naive cats. This study suggests that while our current DNA vaccines may not produce sterilizing immunity against more virulent isolates of FIV, they may nevertheless significantly reduce the impact of infection.

• Publisher: Elsevier Ltd,Elsevier
• Subject: Amino Acid Sequence / Animals / Antibodies, Viral - biosynthesis / Base Sequence / Biological and medical sciences / Cats / Cytokine / Defective Viruses - enzymology / Defective Viruses - genetics / Defective Viruses - immunology / DNA vaccination / DNA, Viral - genetics / Epidemiology. Vaccinations / Feline Acquired Immunodeficiency Syndrome - immunology / Feline Acquired Immunodeficiency Syndrome - prevention & control / Feline immunodeficiency virus / FIV / Fundamental and applied biological sciences. Psychology / General aspects / Genes, Viral / Immunodeficiency Virus, Feline - enzymology / Immunodeficiency Virus, Feline - genetics / Immunodeficiency Virus, Feline - immunology / Immunodeficiency Virus, Feline - pathogenicity / Infectious diseases / Integrases - genetics / Interleukin-12 - administration & dosage / Interleukin-18 - administration & dosage / Medical sciences / Microbiology / Molecular Sequence Data / Proviruses - isolation & purification / RNA-Directed DNA Polymerase - genetics / Sequence Deletion / T-Lymphocytes, Cytotoxic - immunology / Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies / Vaccines, DNA - administration & dosage / Vaccines, DNA - pharmacology / Viral Vaccines - administration & dosage / Viral Vaccines - pharmacology / Virology / Virulence / Virus Replication - genetics