The present invention is based on the development of a dual promoter
system (preferably a RNA pol I-pol II system) for the efficient
intracellular synthesis of viral RNA. The resultant minimal plasmid-based
system may be used to synthesize any RNA virus, preferably viruses with a
negative single stranded RNA genome. The viral product of the system is
produced when the plasmids of the system are introduced into a suitable
host cell. One application of the system is production of attenuated,
reassortant influenza viruses for use as antigens in vaccines. The
reassortant viruses generated by cotransfection of plasmids may comprise
genes encoding the surface glycoproteins hemagglutinin and neuraminidase
from an influenza virus currently infecting the population and the
internal genes from an attenuated influenza virus. An advantageous
property of the present invention is its versatility; the system may be
quickly and easily adapted to synthesize an attenuated version of any RNA
virus. Attenuated or inactivated RNA viruses produced by the present
invention may be administered to a patient in need of vaccination by any
of several routes including intranasally or intramuscularly.