US 7,517,531 B2
Dengue tetravalent vaccine containing a common 30 nucleotide deletion in the 3′-UTR of dengue types 1,2,3, and 4, or antigenic chimeric dengue viruses 1,2,3, and 4
Stephen S. Whitehead, Montgomery Village, Md. (US); Brian R. Murphy, Bethesda, Md. (US); Lewis Markoff, Bethesda, Md. (US); Barry Falgout, Rockville, Md. (US); Joseph Blaney, Frederick, Md. (US); and Kathryn Hanley, Las Cruces, N. Mex. (US)
Assigned to The United States of America as represented by the Department of Health and Human Services, Washington, D.C. (US)
Filed on Oct. 21, 2004, as Appl. No. 10/970,640.
Application 10/970640 is a continuation of application No. PCT/US03/13279, filed on Apr. 25, 2003.
Claims priority of provisional application 60/377860, filed on May 03, 2002.
Claims priority of provisional application 60/436500, filed on Dec. 23, 2002.
Prior Publication US 2007/0009552 A1, Jan. 11, 2007
Int. Cl. A61K 39/295 (2006.01); C12N 7/04 (2006.01)
U.S. Cl. 424—202.1  [424/218.1; 424/199.1; 424/205.1; 435/235.1; 435/320.1; 435/236] 42 Claims
OG exemplary drawing
 
1. A tetravalent immunogenic composition comprising
a) a first attenuated virus that is immunogenic against dengue serotype 1,
b) a second attenuated virus that is immunogenic against dengue serotype 2,
c) a third attenuated virus that is immunogenic against dengue serotype 3, and
d) a fourth attenuated virus that is immunogenic against dengue serotype 4,
wherein each of a), b), c) and d) comprises a nucleic acid comprising
i) a first nucleotide sequence encoding at least one structural protein from a first dengue virus,
ii) a second nucleotide sequence encoding nonstructural proteins from the first dengue virus or a second dengue virus, and
iii) a 3′ untranslated region, wherein the 3′ untranslated region contains a deletion of about 30 nucleotides corresponding to the TL2 stem-loop structure, and wherein both the 3′ untranslated region and the second nucleotide sequence encoding nonstructural proteins are from either the first dengue virus or the second dengue virus;
wherein the tetravalent immunogenic composition is not rDEN1/4Δ30, rDEN2/4Δ30, rDEN3/4Δ30, rDEN4Δ30.