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Nonsegmented Negative-Strand Viruses as Vaccine Vectors

The live-virus vector era began in 1983, when Smith, Mackett, and Moss constructed a recombinant vaccinia virus expressing hepatitis B surface antigen and demonstrated the induction of hepatitis B-specific antibodies in rabbits immunized with the recombinant virus (113). Subsequently, live-virus vectors were developed with other DNA viruses, such as adenoviruses and herpesviruses, and with positive-strand RNA viruses, such as alphaviruses and flaviviruses. The vaccine vector potential of the large group of nonsegmented negative-strand RNA viruses (NNSV) remained unexplored largely due to the lack of infectivity of their genomic RNA in cell culture and the absence of a mechanism for recombinational insertion of foreign genes. The NNSV (order Mononegavirales) comprise four families: Rhabdoviridae, represented by vesicular stomatitis virus (VSV) and rabies virus (RV); Paramyxoviridae, including Sendai virus (SeV), human parainfluenza virus types 1, 2, 3, and 4 (HPIV1 to -4), measles and mumps viruses, Newcastle disease virus (NDV), and human respiratory syncytial and metapneumoviruses (HRSV and HMPV); Filoviridae, containing Ebola and Marburg viruses; and Bornaviridae, containing Borna disease virus. In 1994, Schnell, Mebatsion, and Conzelmann developed a reverse genetic system for RV that allowed the recovery of infectious virus entirely from cloned cDNA (102). This was followed quickly by the development of reverse genetic systems for numerous other NNSV (17, 22, 33, 50, 55, 69, 73, 76, 83, 133). This review will focus on the use of NNSV, in particular members of the Rhabdoviridae and Paramyxoviridae, as live vaccine vectors.