US 7,846,455 B2 · Attenuated chimeric respiratory syncytial virus

Abstract

Chimeric respiratory syncytial virus (RSV) and vaccine compositions thereof are produced by introducing one or more heterologous gene(s) or gene segment(s) from one RSV subgroup or strain into a recipient RSV backround of a different subgroup or strain. The resulting chimeric RSV virus or subviral particle is infectious and attenuated, preferably by introduction of selected mutations specifying attenuated phenotypes into a chimeric genome or antigenome to yield, for example, temperature sensitive (ts) and/or cold adapted (ca) vaccine strains. Alternatively, chimeric RSV and vaccine compositions thereof incorporate other mutations specifying desired structural and/or phenotypic characteristics in an infectious chimeric RSV. Such chimeric RSV incorporate desired mutations specified by insertion, deletion, substitution or rearrangement of one or more selected nucleotide sequence(s), gene(s), or gene segment(s) in a chimeric RSV clone. This provides a method for development of novel vaccines against diverse RSV strains by using a common attenuated backbone as a vector to express protective antigens of heterologous strains. The immune system of an individual is stimulated to induce protection against natural RSV infection, preferably in a multivalent manner to achieve protection against multiple RSV strains and/or subgroups.

Claims11

Dependent claims

An infectious chimeric respiratory syncytial virus (RSV) comprising a major nucleocapsid (N) protein, a nucleocapsid phosphoprotein (P), a large polymerase protein (L), a RSV M2 ORF1 RNA polymerase elongation factor (M2(ORF1)), and a partial or complete genome or antigenome of RSV A comprising genome segments encoding antigenic determinants of RSV B F and G glycoproteins, wherein the RSV A genome or antigenome contains the following attenuating mutations:

i) a mutation encoding V267I in the N gene;
ii) a mutation encoding C319Y in the L gene;
iii) a mutation encoding H1690Y in the L gene;
iv) a mutation encoding Q831L in the L gene;
v) a mutation encoding D1183E in the L gene;
vi) a point mutation T to C at nucleotide 7605 of the gene start of the M2 gene;
and wherein the RSV A genome or antigenome further contains at least one of the following:
a mutation encoding Y1321N in the L gene;
or
a deletion of the SH open reading frame.

7 more elements

Dependencies are inferred from the claim text.

Attenuated chimeric respiratory syncytial virus

Life of this patent

Attenuated chimeric respiratory syncytial virus

Life of this patent

Abstract

Claims11