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 TLR9 agonist and a TLR 2/6 agonist to the individual.
1. A method of inhibiting or attenuating a bacteria infection comprising administering a pharmaceutically acceptable composition comprising an effective amount of a type C CpG oligodeoxynucleotide (ODN) and PAM2CSK4 to an individual that has or is at risk of developing or acquiring a bacteria infection, wherein the composition does not have an antigen as an active ingredient, and wherein administering both the Type C ODN and PAM2CSK4 inhibits or attenuates said bacterial infection.
2. The method of claim 1 , wherein the type C CpG ODN comprises
1) one or more TCG sequences at 5′ end of the nucleic acid or
2) (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.
3. The method of claim 2 , wherein the type C CpG ODN comprises the sequence TCGTCG.
4. The method of claim 3 , wherein the type C CpG ODN is ODN2395 or ODNM362 or ODN10101.
5. The method of claim 1 , wherein the bacteria is Bacillus anthracis, Yersinia pestis, Francisella tularensis, Pseudomonas aeruginosa, Staphylococcus aureus, S. maltophilia, Burkholderia spp. or Moraxella spp.
6. The method of claim 1 , wherein the type C CpG ODN and the PAM2CSK4 are administered in a nebulized or aerosolized formulation.
7. The method of claim 1 , wherein the effective amount of the type C CpG ODN and the PAM2CSK4 is deposited in the lungs of the individual.
8. The method of claim 1 , wherein the type C CpG ODN and the PAM2CSK4 is administered in an amount of from about 0.1 mg/kg to about 100 mg/kg of the individual's body weight.
9. The method of claim 6 , wherein the individual is administered the type C CpG ODN in a concentration of 20 μg/ml.
10. A method of inhibiting or attenuating a bacteria infection comprising administering an effective amount of a type C CpG oligodeoxynucleotide (ODN) and PAM2CSK4 in the same or separate compositions to an individual that has or is at risk of developing or acquiring the bacteria infection, wherein the same or separate compositions does not have an antigen as an active ingredient, and wherein administering both the type C ODN and PAM2CSK4 inhibits or attenuates said bacterial infection.
11. The method of claim 10 , wherein the type C CpG ODN comprises
1) one or more TCG sequences at 5′ end of the nucleic acid or
2) (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.
12. The method of claim 10 , wherein the type C CpG ODN comprises the sequence TCGTCG and comprises phosphorothioate.
13. The method of claim 10 , wherein the type C CpG ODN is ODN2395 or ODNM362 or ODN10101.
14. The method of claim 10 , wherein the bacteria is Bacillus anthracis, Yersinia pestis, Francisella tularensis, Pseudomonas aeruginosa, Staphylococcus aureus, S. maltophilia, Burkholderia spp. or Moraxella spp.
15. The method of claim 10 , wherein the type C CpG ODN is ODN2395 or ODNM362 or ODN10101.
16. The method of claim 4 , wherein the type C CpG ODN is ODNM362.
17. The method of claim 15 , wherein the type C CpG ODN is ODNM362.
18. A method of stimulating innate resistance in an individual comprising administering a type C CpG oligodeoxynucleotide (ODN) and PAM2CSK4 in the same or separate compositions to an individual that has or is at risk of developing or acquiring a bacteria infection, wherein the same or separate compositions does not have an antigen as an active ingredient, wherein administering both the type C ODN and PAM2CSK4 stimulates innate resistance that inhibits a bacterial infection in the individual.
19. The method of claim 18 , wherein the type C CpG ODN comprises
1) one or more TCG sequences at 5′ end of the nucleic acid or
2) (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.
20. The method of claim 18 , wherein the type C CpG ODN is ODN2395 or ODNM362 or ODN10101.
21. The method of claim 20 , wherein the type C CpG ODN is ODNM362.
22. The method of claim 1 , wherein the ODN and PAM2CSK4 are essentially free of pathogenic microbes.
23. The method of claim 10 , wherein the composition(s) are essentially free of pathogenic microbes.
24. The method of claim 18 , wherein the composition(s) are essentially free of pathogenic microbes.