US 12,168,675 B2
Virus-like particles and methods of use
Gary J. Nabel, Chestnut Hill, MA (US); Srinivas Rao, Columbia, MD (US); and Wataru Akahata, Kensington, MD (US)
Assigned to The United States of America, as represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US)
Filed by The United States of America, as represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US)
Filed on Jun. 7, 2023, as Appl. No. 18/331,083.
Application 16/199,671 is a division of application No. 15/279,592, filed on Sep. 29, 2016, granted, now 10,138,277, issued on Nov. 27, 2018.
Application 15/279,592 is a division of application No. 13/982,986, granted, now 9,487,563, issued on Nov. 8, 2016, previously published as PCT/US2012/023361, filed on Jan. 31, 2012.
Application 18/331,083 is a continuation of application No. 17/410,182, filed on Aug. 24, 2021, granted, now 11,718,647.
Application 17/410,182 is a continuation of application No. 16/199,671, filed on Nov. 26, 2018, granted, now 11,098,084, issued on Aug. 24, 2021.
Claims priority of provisional application 61/501,012, filed on Jun. 24, 2011.
Claims priority of provisional application 61/438,236, filed on Jan. 31, 2011.
Prior Publication US 2023/0295242 A1, Sep. 21, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 14/005 (2006.01); A61K 39/12 (2006.01); C12N 7/00 (2006.01); A61K 39/00 (2006.01)
CPC C07K 14/005 (2013.01) [A61K 39/12 (2013.01); C12N 7/00 (2013.01); A61K 2039/5258 (2013.01); A61K 2039/53 (2013.01); A61K 2039/55566 (2013.01); A61K 2039/575 (2013.01); C12N 2770/36122 (2013.01); C12N 2770/36123 (2013.01); C12N 2770/36134 (2013.01); C12N 2770/36151 (2013.01)] 12 Claims
 
1. An immunogenic composition, comprising:
(A) a first virus-like particle (VLP) comprising at least one altered viral protein selected from the group consisting of:
an Eastern equine encephalitis virus (EEEV) E2 protein comprising one or more alterations, relative to the wild-type amino acid sequence, at one or more amino acid locations corresponding to one or more amino acid locations selected from the group consisting of amino acid 170, amino acid 200, amino acid 233, amino acid 234, amino acid 251, and amino acid 256 of Chikungunya virus (CHIKV) E2 protein; and
an EEEV capsid protein comprising one or more alterations, relative to the wild-type amino acid sequence, at a charged amino acid residue in the Nuclear Localization Signal (NLS); and
wherein the at least one altered viral protein is capable of self-assembling into a VLP; and, wherein the one or more alterations enhance VLP production;
(B) a second VLP comprising at least one altered viral protein selected from the group consisting of:
an Western equine encephalitis virus (WEEV) E2 protein comprising one or more alterations, relative to the wild-type amino acid sequence, at one or more amino acid locations corresponding to one or more amino acid locations selected from the group consisting of amino acid 170, amino acid 200, amino acid 233, amino acid 234, amino acid 251, and amino acid 256 of CHIKV E2 protein; and
an EEEV capsid protein comprising one or more alterations, relative to the wild-type amino acid sequence, at a charged amino acid residue in the NLS;
wherein the at least one altered viral protein is capable of self-assembling into a VLP; and, wherein the one or more alterations enhance VLP production; and
(C) a third VLP comprising at least one altered viral protein selected from the group consisting of:
an Venezuelan equine encephalitis virus (VEEV) E2 protein comprising one or more alterations, relative to the wild-type amino acid sequence, at one or more amino acid locations corresponding to one or more amino acid locations selected from the group consisting of amino acid 170, amino acid 200, amino acid 233, amino acid 234, amino acid 251, and amino acid 256 of CHIKV E2 protein; and
an EEEV capsid protein comprising one or more alterations, relative to the wild-type amino acid sequence, at a charged amino acid residue in the NLS; and
wherein the at least one altered viral protein is capable of self-assembling into a VLP; and, wherein the one or more alterations enhance VLP production.