Halogenated Xanthenes as Vaccine Adjuvants

An improved vaccine composition that contains a vaccine-effective amount of a predetermined immunogen and about 0.001% by weight to about 10% by weight of one or more excipients dissolved or dispersed in a pharmaceutically acceptable diluent in which the improvement comprises an adjuvant-effective amount of a halogenated xanthene (HX) compound as discussed above that is also dissolved or dispersed with the immunogen in that pharmaceutically acceptable diluent.

A method of inducing Type I interferon (IFN) response in a mammalian subject that presents with a microbial infection that comprises administering a STING dimerization-inducing amount of a halogenated xanthene (HX), a pharmaceutically acceptable salt, an amide thereof whose nitrogen atom is unsubstituted, substituted with one or two C1-C4 alkyl groups that are the same or different or together with the amido nitrogen form a 5- or 6-membered ring, a C1-C4 alkyl ester thereof, an aromatic derivative thereof, wherein the aromatic derivative is an ester or amide formed from an alcohol or monosubstituted amine having a 5- or 6-membered aromatic ring, or a 5,6- or 6,6-fused aromatic ring system that contains 0, 1 or 2 hetero ring atoms that are independently nitrogen, oxygen or sulfur.

A method of inducing Type I interferon (IFN) response in a mammalian subject having a cancerous tumor or a hematologic malignancy that comprises systemically administering a STING dimerization-inducing amount of a halogenated xanthene (HX), a pharmaceutically acceptable salt, an amide thereof whose nitrogen atom is unsubstituted, substituted with one or two C1-C4 alkyl groups that are the same or different or together with the amido nitrogen form a 5- or 6-membered ring, a C1-C4 alkyl ester thereof, an aromatic derivative thereof, wherein the aromatic derivative is an ester or amide formed from an alcohol or monosubstituted amine having a 5- or 6-membered aromatic ring, or a 5,6- or 6,6-fused aromatic ring system that contains 0, 1 or 2 hetero ring atoms that are independently nitrogen, oxygen or sulfur.

A method of enhancing a mammalian immunogen-specific immune response that comprises contacting mammalian cells present in vivo with an adjuvant-effective amount of a halogenated xanthene (HX), a pharmaceutically acceptable salt, an amide thereof whose nitrogen atom is unsubstituted, substituted with one or two C1-C4 alkyl groups that are the same or different or together with the amido nitrogen form a 5- or 6-membered ring, a C1-C4 alkyl ester thereof, an aromatic derivative thereof, wherein the aromatic derivative is an ester or amide formed from an alcohol or monosubstituted amine having a 5- or 6-membered aromatic ring, or a 5,6- or 6,6-fused aromatic ring system that contains 0, 1 or 2 hetero ring atoms that are independently nitrogen, oxygen or sulfur, and an immunogen to which said response is to be enhanced.