Methods of inducing human immunodeficiency virus-specific immune responses in a host comprising nasally administering compositions comprising a naonemulsion and recombinant GP120 immunogen
The present invention relates to methods and compositions for the stimulation of immune responses. Specifically, the present invention provides methods of inducing an immune response to human immunodeficiency virus (HIV) in a subject (e.g., a human subject) and compositions useful in such methods (e.g., a nanoemulsion comprising HIV or antigenic portion thereof).
1. A method of inducing a human immunodeficiency virus (HIV) specific immune response in a subject comprising nasally administering to the subject an effective amount of an immunogenic composition comprising a nanoemulsion and an immunogen, wherein the immunogen comprises recombinant gp120 and wherein the nanoemulsion comprises oil, ethanol, TWEEN 20 or TWEEN 80, cetylpyridinium chloride and water, to generate a HIV specific immune response comprising generation of broadly reactive gp120-specific antibodies with HIV-neutralizing activity.
2. The method of claim 1 , wherein the gp120-specific antibodies with HIV-neutralizing activity display neutralizing activity against three or more primary HIV isolates selected from the group consisting of BG1168.1, SS1196.11, 3988.25, QH0692.42 and 5768.4.
3. The method of claim 1 , wherein the gp120-specific antibodies with HIV-neutralizing activity display neutralizing activity against four or more primary HIV isolates selected from the group consisting of BG1168.1, SS1196.11, 3988.25, QH0692.42 and 5768.4.
4. The method of claim 1 , wherein the gp120-specific antibodies with HIV-neutralizing activity display neutralizing activity against HIV isolates BG1168.1, SS1196.11, 3988.25, QH0692.42 and 5768.4.
5. The method of claim 4 , wherein the gp120-specific antibodies with HIV-neutralizing activity are detectable in bronchial and vaginal mucosal surfaces in the subject.
6. The method of claim 1 , wherein the immune response comprises generation of a Th1 type cellular immune response against both autologous and heterologous gp120.
7. The method of claim 6 , wherein the Th1 type cellular immune response comprises generation of a level of IFN-γ that is at least ten fold greater than the level of IFN-γ generated in a control subject administered an equal amount of recombinant gp120 suspended in saline.
8. The method of claim 1 , wherein the immune response comprises a systemic IgG response to the HIV.
9. The method of claim 8 , wherein the systemic 1gG response comprises generation of a gp120-specific IgG antibody titer that is at least two fold greater than the gp120-specific IgG antibody titer generated in a control subject administered an equal amount of recombinant gp120 suspended in saline.
10. The method of claim 8 , wherein the systemic IgG response comprises generation of a gp120-specific IgG antibody titer that is at least 100fold greater than the gp120-specific IgG antibody titer generated in a control subject administered an equal amount of recombinant gp120 suspended in saline.
11. The method of claim 8 , wherein the systemic IgG response comprises generation of a gp120-specific IgG antibody titer that is at least 1000fold greater than the gp120-specific IgG antibody titer generated in a control subject administered an equal amount of recombinant gp120 suspended in saline.
12. The method of claim 1 , wherein the immune response comprises a mucosal IgA response to the HIV.
13. The method of claim 1 , wherein the immunogenic composition comprises between 15 and 75 μg of recombinant gp120.
14. The method of claim 1 , wherein the immunogenic composition comprises 0.1 - 20% nanoemulsion solution.
15. The method of claim 1 , wherein the nanoemulsion has a mean droplet size of about 200-800 nanometers.