US 6,982,087 B2
Vectors derived from South African Arbovirus No. 86
Robert E. Johnston, Chapel Hill, N.C. (US); Mark T. Heise, Durham, N.C. (US); and Dennis Simpson, Hillsborough, N.C. (US)
Assigned to The University of North Carolina at Chapel Hill, Chapel Hill, N.C. (US)
Appl. No. 10/363,603
PCT Filed Sep. 06, 2001, PCT No. PCT/US01/27644
§ 371(c)(1), (2), (4) Date Jul. 07, 2003,
PCT Pub. No. WO02/20721, PCT Pub. Date Mar. 14, 2002.
Claims priority of provisional application 60/230663, filed on Sep. 07, 2000.
Prior Publication US 2004/0030117 A1, Feb. 12, 2004
Int. Cl. A61K 39/12 (2006.01); C12N 7/01 (2006.01); C12N 15/40 (2006.01); C12N 15/86 (2006.01)
U.S. Cl. 424—199.1 48 Claims
 
1. A South African Arbovirus No. 86 (S.A.AR86) genomic RNA, said S.A.AR86 genomic RNA comprising:
(a) S.A.AR86 nonstructural protein (nsp) and/or S.A.AR86 structural protein coding sequences, wherein the S.A.AR86 nonstructural protein and/or structural protein coding sequences encode an attenuating mutation selected from the group consisting of:
(i) an attenuating mutation in the cleavage domain between the nsp1 and nsp2 coding sequences;
(ii) an attenuating mutation that results in a termination codon at nsp3 amino acid position 537,
(iii) an attenuating mutation comprising a substitution mutation at nsp3 amino acid position 385,
(iv) an attenuating mutation comprising an insertion of at least 8 amino acids following nsp3 amino acid position 385,
(v) an attenuating mutation comprising a substitution at E2 amino acid position 243, and
(vi) a combination of the attenuating mutations of (i) to (v)
(b) a heterologous nucleotide sequence; and
(c) an alphavirus capsid enhancer sequence operatively associated with said heterologous nucleotide sequence.