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225 Measles Vaccine as a Potential Vector for AIDS Vaccination
F. Tangy*1, C. Combredet1, V. Labrousse-Najburg1, C. Lorin1, F. Delebecque1, Z. Wang2, M. Caballero2, A. Zuniga2, M. Billeter2, H. Naim2, L. Mollet1, H. McClure3, M. Feinberg 3, M. Kazanji4, and H. Contamin4
1Pasteur Inst., Paris, France; 2Univ. of Zurich, Switzerland; 3Emory Univ., Vaccine Res. Ctr., Atlanta, GA, USA; and 4Pasteur Inst., Cayenne, French Guyana
Background: Because more than 90% of the persons infected by HIV are living in developing countries with no access to HAART, only a preventive vaccine intended for children and adolescents has the potential to contain the AIDS pandemic. This vaccine should be safe, cheap, and effective after a single or a few doses. Live-attenuated measles virus (MV) vaccine has been used for more than 30 years. It is safe, cheap, and induces strong, protective, and long-lasting humoral and cellular immune responses after a single injection in 6- to 12-month-old children.
Methods: With the aim to produce a preventive pediatric candidate AIDS vaccine intended for children living in developing countries, we constructed a set of recombinant attenuated measles viruses (Edmonston B strain) in which different SIV and HIV genes were introduced: Gag, Pol, Env, Tat, Rev, and Nef. Immunization experiments were performed on different animal models (macaques, squirrel monkeys, and transgenic mice made susceptible for MV infection).
Results: The recombinant viruses were produced using a helper-cell-based rescue system. They replicated comparably to the progenitor Edmonston B Measles virus and were genetically stable during at least 12 passages in vitro. The expression of the different SIV and HIV transgenes lasted over all passages. Preliminary experiments showed that in vitro restimulation and in vivo immunization with the recombinant measles viruses induced both humoral and cellular long-lasting responses against measles and the products of the transgenes.
Conclusions: Recombinant attenuated measles viruses have the potential to induce immune responses against HIV proteins. The excellent stability of this live vector and its large capacity of insertion (up to 5 kb can be inserted into the 16-kb MV genome) make it a candidate suited for the development of a safe and effective pediatric vaccine.
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