Live-attenuated virus vaccines for respiratory syncytial and parainfluenza viruses: applications of reverse genetics
J. Clin. Invest. Brian R. Murphy, et al. 110:21 doi:10.1172/JCI16077 [
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Figure 3Use of reverse genetics to introduce new combinations of mutations into rRSV A2 of subgroup A and to expedite the development of a live-attenuated vaccine virus specific to RSV subgroup B. (
a) Recombinant wild-type RSV (rRSV A2 wt) was used as a backbone for the introduction of the five point mutations of
cpRSV (cp), two attenuating mutations from RSV
cpts248/404 (248-L and 404-M2), and one attenuating mutation from RSV
cpts530/1030 (1030) to create the new vaccine candidate rRSVA2
cpts248/404/1030. (
b) The genes encoding the F and G antigenic determinants of the subgroup B RSV B1 wt virus were substituted into the backbone of rRSV A2 wt to create the chimeric rRSV AB wt virus, which was then attenuated by the introduction of three mutations of
cpRSV, two mutations from RSV
cpts248/404, and one mutation from RSV
cpts530/1030. The level of viral replication in the respiratory tract of rodents or chimpanzees is indicated on the right.