An HTLV-I/II vaccine: from animal models to clinical trials?
A human T-lymphotropic virus type I/II (HTLV-I/II) vaccine is necessary in view of two etiologically related, life-threatening diseases, namely, adult T-cell leukemia/lymphoma and tropical spastic paraparesis/HTLV-I-associated myelopathy. When the risk of developing autoimmune diseases such as uveitis, polymyositis, and arthritis is included, one can estimate the life-long risk of infected individuals to develop an HTLV associated pathology as approximately 10%. The populations at risk are, in a large majority, from developing countries but the epidemic of HTLV-II infection in intravenous drug users (IVDU) represents a possible reservoir for dissemination in the general population. The number of HTLV-I-infected individuals (15 to 25 million), together with the severity of associated disease, justifies the development of a vaccine. Different vaccine preparations have been developed, using mostly recombinant pox and adenoviruses, but DNA plasmid technology will soon become a feasible approach. Various animal models exist for experimental viral infections, involving rats, rabbits, or monkeys, but up to now, neither hematological nor neurological disorders have been induced by HTLV infection in such animal models. For long-term protection from HTLV-I-associated diseases, vaccination should induce both neutralizing antibodies and specific cell-mediated immunity. This will require the incorporation of both env and gag coding sequences in the vaccine preparations. Preventive clinical trials may involve different cohorts of seronegative young girls from endemic areas prior to sexual activity and IVDU in the industrialized world. In parallel, one should consider therapeutic vaccine trials in HTLV-I-positive mothers and IVDU to protect them against disease development. The observed rate of seroconversion in these different cohorts makes such trials feasible.
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Unité d'Epidémiologie des Virus Oncogènes, Institut Pasteur, Paris, France.
Kazanji
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D000818:Animals; D000917:Antibody Formation; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods*; D004195:Disease Models, Animal; D015683:Gene Products, gag / Q000276:immunology; D000882:Haplorhini; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D015367:Human T-lymphotropic virus 2 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D015458:Leukemia, T-Cell / Q000276:immunology* / Q000517:prevention & control / Q000821:virology*; D015493:Paraparesis, Tropical Spastic / Q000276:immunology* / Q000517:prevention & control; D011817:Rabbits; D051381:Rats; D011995:Recombination, Genetic / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D014759:Viral Envelope Proteins / Q000276:immunology
D019496:Cancer Vaccines; D015683:Gene Products, gag; D014759:Viral Envelope Proteins