Modified human rotaviruses and uses therefor
AssigneeMurdoch Childrens Research Institute
InventorsCarl Kirkwood, Ruth Frances Bishop, Graeme Laurence Barnes
Life of this patent
Estimating the term…
Abstract
The present disclosure relates generally to the field of viral vaccines. Particularly, the present disclosure provides a modified Vero-adapted human rotavirus strain and a culturing method to produce high titer virus, a rotavirus vaccine, vaccination protocols and diagnostic and prognostic assays.
Claims22
A method for culturing a strain of rotavirus (RV), said method comprising subjecting an aliquot or inoculum of RV to trypsinization and culturing the trypsinized RV in Vero cells or a Vero cell-derived cell line for a time and under conditions sufficient for the RV to undergo a genetic modification resulting in an amino acid change in one or more of VP1, VP3, VP4, NSP4 and/or NSP5/6 and/or nucleotide change in one or more of VP1, VP3, VP4, NSP2, NSP4 and/or NSP5/6.
A method for generating an attenuated RV3 in Vero cells, said method comprising trypsinizing an aliquot or inoculum of an attenuated RV3 and culturing the trypsinized RV3 with Vero cells or a Vero cell-derived cell line for a time and under conditions sufficient for a genetic modification to occur selected from the list provided in Table 2 or Table 5 compared to MA104-adapted RV3.
An isolated Vero-adapted RV3 comprising one or more mutations selected from the list consisting of a codon in NSP4 selected from 53, 76, 85, 162 and 165, a codon in NSP5/6 selected from 46 and 112, a codon in VP1 selected from 886, a codon in VP3 selected from 643 and 785, and a codon in VP4 selected from 43, 374, 385, 388, 442 and 756 and/or a nucleotide in NSP2 selected from 433, a nucleotide in NSP4 selected from 197, 267, 294, 525 and 534, a nucleotide in NSP5/6 selected from 158, 165 and 355, a nucleotide in VP1 selected from 2692, a nucleotide in VP3 selected from 343, 1366, 1744, 1976 and 2402 and/or a nucleotide in VP4 selected from 136, 369, 1130, 1162, 1171, 1334 and 2276.
An attenuated live or killed RV composition comprising an RV having a genetic modification selected from one or more mutations in VP1, VP3, VP4, NSP4 and/or NSP5/6, said composition further comprising one or more pharmaceutically acceptable carriers, diluents and/or excipients.
A method for vaccinating a human subject against RV infection, said method comprising administering to said subject an effective amount of a live, attenuated Vero-adapted RV3 or a killed Vero-adapted RV3 for a time and under conditions sufficient to generate an immune response against RV infection.
A method for treating a human subject with an RV infection or at risk of developing an RV infection or re-infection said method comprising administering to said subject an effective amount of a live, attenuated Vero-adapted RV3 or a killed Vero-adapted RV3 for a time and under conditions sufficient to generate an immune response against RV infection.
Use of a Vero-RV in the manufacture of a medicament in the treatment of RV infection in a subject.
An isolated antibody to a Vero-RV.
A method for detecting or monitoring a Vero-RV said method comprising screening for a genetic modification resulting in an amino acid change in one or more of VP1, VP3, VP4, NSP4 and/or NSP5/6 and/or nucleotide change in one or more of VP1, VP3, VP4, NSP2, NSP4 and/or NSP5/6.
Use of a Vero-RV in the manufacture of a diagnostic to monitor infection, treatment, epidemiology or adaptation of a Vero-RV.
Dependencies are inferred from the claim text.