Recombinant vector derived from live attenuated measles virus: potential for flavivirus vaccines

Abstract

The measles vaccine is one of the best vaccines currently available. Over the last 30 years, it has been administered to hundreds of millions of children and has proved to be both effective and safe. This attenuated live virus induces life-long immunity after only one or two injections. It is produced on a large scale, with ease, in many countries and is distributed at low cost. These excellent characteristics led us to consider its use as a pediatric live vector, to simultaneously immunize children or adolescents against measles and other viral infections, such as human immunodeficiency virus (HIV) or flavivirus infections. For this purpose, we have developed a vector derived from the live attenuated Schwarz strain of the measles virus (MV). We have demonstrated the capacity of this vector to strongly and stably express genes encoding proteins from HIV and to induce specific humoral and cellular immune responses in vivo. Importantly, we observed that, at least in animal models, the vector can bypass measles vaccine pre-existing immunity when two doses of recombinant vaccine are administered. Clinical trials are in progress to confirm this observation in immunized adults. We also produced MV vectors expressing proteins from West Nile virus and other flaviviruses, which in the case of West Nile virus, protected against experimental challenge. Recombinant live attenuated MV might be used as bivalent vaccination vector to mass immunize children and adolescents against both measles and flaviviral diseases such as Dengue or Japanese Encephalitis in the developing world.