US 12,409,213 B2
Live attenuated oral vaccine against shigellosis and typhoid fever
Yun Wu, Rockville, MD (US); Dennis J. Kopecko, Silver Spring, MD (US); B. Kim Lee Sim, Gaithersburg, MD (US); and Stephen L. Hoffman, Gaithersburg, MD (US)
Assigned to Sanaria Inc., Rockville, MD (US)
Filed by Sanaria Inc., Rockville, MD (US)
Filed on Apr. 25, 2022, as Appl. No. 17/660,558.
Application 17/660,558 is a division of application No. 16/897,999, filed on Jun. 10, 2020, granted, now 11,324,814.
Application 16/897,999 is a division of application No. 15/742,459, granted, now 10,695,415, issued on Jun. 30, 2020, previously published as PCT/US2016/041192, filed on Jul. 6, 2016.
Claims priority of provisional application 62/189,083, filed on Jul. 6, 2015.
Prior Publication US 2022/0323562 A1, Oct. 13, 2022
Int. Cl. A61K 39/112 (2006.01); A61K 39/00 (2006.01); A61K 39/116 (2006.01)
CPC A61K 39/0283 (2013.01) [A61K 39/0275 (2013.01); A61K 39/116 (2013.01); A61K 2039/522 (2013.01); A61K 2039/523 (2013.01); A61K 2039/543 (2013.01); A61K 2039/70 (2013.01); Y02A 50/30 (2018.01)] 11 Claims
 
1. A method of treating or reducing the incidence of shigellosis in a human subject comprising oral administration of one or more doses of a vaccine, said vaccine comprising a transgenic Ty21a Salmonella typhi Ty21a, which comprises (i) a heterologous Shigella sonnei O-antigen biosynthetic gene region comprising a wzz gene, wherein the wzz gene comprises a DNA sequence that shares at least 95% sequence identity with the DNA sequence of nucleic acids 4,511,904 to 4,513,010 of SEQ ID NO: 4; and (ii) a heterologous acid resistance biosynthetic gene system comprising one or more YbaS genes; wherein said heterologous Shigella sonnei O-antigen biosynthetic gene region and said heterologous acid resistance biosynthetic gene system are both integrated into the Salmonella typhi Ty21a chromosome, and wherein:
a. the heterologous Shigella sonnei O-antigen is stably expressed;
b. the one or more YbaS genes are stably expressed;
c. said transgenic Salmonella typhi Ty21a is more acid stable at pH 2.5 than Salmonella typhi Ty21a without the integrated acid resistance biosynthetic gene system;
d. an immune response is elicited against virulent Shigella sonnei challenge; and,
e. an immune response is elicited against virulent Salmonella typhi challenge.