Compositions for stimulation of mammalian innate immune resistance to pathogens
View Patent ↗Embodiments of the invention are directed to methods of treating, inhibiting or attenuating a microbial infection in an individual who has or is at risk for developing such an infection, comprising the step of administering an effective amount of a StIR composition to the individual.
1. A pharmaceutically acceptable composition comprising a type C CpG oligodeoxynucleotide (ODN) and a TLR2/6 agonist, wherein the TLR2/6 agonist is PAM2CSK4 and wherein the composition does not further comprise an active ingredient that is an antigen.
2. The composition of claim 1 , wherein the composition is formulated for nebulization.
3. The composition of claim 1 , wherein the type C CpG ODN is ODN2395, ODN M362, or ODN10101.
4. The composition of claim 1 , wherein the type C CpG ODN is ODN M362.
5. The composition of claim 1 , wherein the composition is aerosolized.
6. The composition of claim 1 , wherein the type C CpG ODN comprises:
(a) one or more TCG sequences at 5′ end of the nucleic acid or
(b) (TCG)n, where n=1 to 3 and
where the (TCG)n sequence is flanked by one to 5 nucleotides on the 5′ end of the (TCG)n sequence.
7. The composition of claim 1 , wherein the type C CpG ODN comprises the sequence TCGTCG.
8. The composition of claim 1 , wherein the type C CpG ODN is in a concentration of 20 μg/ml.
9. A unit dose comprising the composition of claim 1 , wherein the PAM2CSK4 is in a dosage concentration at which maximal cytokine secretion is stimulated from dendritic cells ([DCmax]).
10. A unit dose comprising the composition of claim 1 , wherein the PAM2CSK4 and type C CpG ODN are in a dosage unit concentration at which neutrophilic infiltration of the lung is induced.
11. A unit dose comprising the composition of claim 1 , wherein the PAM2CSK4 and type C CpG ODN are each in a dosage unit concentration of about 0.01 μg/kg to about 100 μg/kg of the individual's body weight.
12. The unit dose of claim 11 , wherein the PAM2CSK4 and type C CpG ODN are each in a dosage unit concentration of about 0.01 μg/kg to about 1 μg/kg of the individual's body weight.
13. The unit dose of claim 11 , wherein the PAM2CSK4 and type C CpG ODN are each in a dosage unit concentration of about 0.01 μg/kg to about 0.1 μg/kg of the individual's body weight.
14. An inhalation device comprising the pharmaceutical composition of claim 1 .
15. The inhalation device of claim 14 , wherein the device is for the delivery of the pharmaceutical composition by nasal inhalation.
16. The inhalation device of claim 14 , wherein the inhalation device is selected from a nebulizer, a metered-dose inhaler, a sprayer, and a dry-powder inhalation device.
17. A nasal spray comprising the pharmaceutical composition of claim 1 .
18. Nasal drops comprising the pharmaceutical composition of claim 1 .
19. A device for nasal administration comprising a pharmaceutically acceptable composition comprising Pam2CSK4 and ODN M362 and wherein the composition does not further comprise an active ingredient that is an antigen.
20. The composition of claim 1 , wherein the composition comprises glycerol.