Hiv vaccine formulations

Abstract

Provided herein are HIV vaccines comprising HIV polypeptide-encoding DNA adsorbed to PLG and/or HIV proteins. Also provided are methods of using these vaccines to generate immune responses in a subject.

1 . An immunogenic composition comprising oligomeric gp140 (o-gp140) and a pharmaceutically acceptable excipient. 
   
   
       2 . The immunogenic composition of  claim 1 , wherein the concentration of o-gp140 is between about 0.1 and 10 mg/mL. 
   
   
       3 . The immunogenic composition of  claim 1 , wherein the concentration of o-gp140 per dose is approximately 100 μg/dose. 
   
   
       4 . The immunogenic composition of  claim 1 , containing:
 (a) 0.4 mg/ml o-gp140, 2.75 mg/ml sodium citrate dihydrate, 0.15 mg/ml citric acid monohydrate, 17.53 mg/ml sodium chloride; 2 mg Env-DNA/ml, 50 mg PLG/ml, and 2 mg Gag-DNA/ml; or   (b) 0.4 mg/ml Env protein and MF59.   
   
   
       5 . The immunogenic composition of  claim 1 , further comprising an adjuvant. 
   
   
       6 . The immunogenic composition of  claim 5 , wherein the adjuvant is MF59 or CpG. 
   
   
       7 . The immunogenic composition of  claim 6 , wherein the adjuvant is MF59 and MF59 comprises 39 mg/ml squalene, 4.7 mg/ml polysorbate 80, 4.7 mg/ml sorbitan trioleate, 2.68 mg/ml sodium citrate dihydrate, 0.17 mg/ml citric acid monohydrate. 
   
   
       8 . An immunogenic composition comprising:
 (a) an HIV Env DNA immunogenic composition, said HIV Env DNA immunogenic composition comprising at least one HIV Env encoding polynucleotide sequence and PLG;   (b) an HIV Gag DNA immunogenic composition, said HIV Gag DNA immunogenic composition comprising at least one HIV Gag-encoding polynucleotide sequence and PLG: and   (c) an HIV protein immunogenic composition, said HIV immunogenic composition comprising o-gp140 and a pharmaceutically acceptable excipient.   
   
   
       9 . A method of generating an immune response in a subject, said method comprising:
 (a) administering to the subject at least one immunogenic composition, said composition comprising:
 (i) a nucleic acid expression vector comprising at least one HIV Gag- or Env-encoding polynucleotide sequence; or 
 (ii) an HIV ogp140; and 
   (b) administering to the subject, at a time subsequent to the administering of step   (a), at least one immunogenic composition, said composition comprising:
 (i) a nucleic acid expression vector comprising at least one HIV Gag- or Env-encoding polynucleotide sequence; or 
 (ii) an HIV ogp140. 
   
   
   
       10 . A method of generating an immune response in a subject, said method comprising:
 (a) administering to said subject at least one HIV DNA immunogenic composition comprising a nucleic acid expression vector comprising at least one HIV Gag- or Env-encoding sequence; and   (b) administering to the subject, at a time subsequent to the administering of step (a), at least one immunogenic composition comprising HIV ogp140.   
   
   
       11 . The method of  claim 10 , wherein step (a) comprises multiple administrations of said at least one HIV DNA immunogenic composition and step (b) comprises multiple administrations of said at least one immunogenic composition comprising HIV ogp 140. 
   
   
       12 . The method of  claim 11 , wherein step (a) comprises two or three administrations at one month intervals; step (b) comprises two or three administrations at 1, 2 or 3 month intervals; and the time between the administrations of step (a) and step (b) is 1 to 5 months. 
   
   
       13 . The method  claim 10 , wherein step (a) comprises administering at least one HIV Gag DNA immunogenic composition and at least one HIV Env DNA immunogenic composition. 
   
   
       14 . The method of  claim 9  wherein step (b) comprises concurrently administering at least one DNA immunogenic composition comprising a nucleic acid expression vector comprising at least one HIV Gag- or Env-encoding sequence and at least one HIV immunogenic composition comprising ogp140. 
   
   
       15 . The method of  claim 14 , wherein step (a) comprises administering at least one HIV Gag DNA immunogenic composition and at least one HIV Env DNA immunogenic composition. 
   
   
       16 . The method of  claim 9 , wherein at least one administration is intramuscular or intradermal. 
   
   
       17 . A method of making oligomeric HIV Env gp140 proteins, comprising the steps of introducing a nucleic acid encoding gp140 into a host cell; culturing the host cell under conditions such that gp140 is expressed in the cell; and isolating o-gp140 protein from the host cell. 
   
   
       18 . The method of  claim 17 , wherein the o-gp140 is secreted from the cell and isolated from the cell supernatant. 
   
   
       19 . A method of making a composition according to  claim 1 , comprising combining o-gp140 with an adjuvant. 
   
   
       20 . The immunogenic composition of  claim 8 , wherein the concentration of PLG is between about 5 and 100 fold greater than the concentration of the nucleic acid expression Vector. 
   
   
       21 . The immunogenic composition of  claim 20 , wherein the concentration of nucleic acid is between about 10 μg/mL and 5 mg/mL and the concentration of the PLG is between about 100 μg/mL and 100 mg/mL. 
   
   
       22 . The immunogenic composition of  claim 8 , wherein the concentration of nucleic acid per dose is between approximately 1 μg/dose and 5 mg/dose and the concentration of the PLG per dose is between about 10 μg/dose and 100 mg/dose. 
   
   
       23 . The immunogenic composition of  claim 8 , wherein the HIV Env DNA immunogenic composition component is an aqueous solution comprising 50.0 mg/ml PLG, 20 mg/ml plasmid DNA, 0.5 mg/ml hexadecyltrimethylammonium bromide, 44 mg/ml mannitol, 14.7 mg/ml sucrose, 0.37 mg/ml EDTA, 1.4 mg/ml sodium citrate dihydrate, and 0.04 mg/ml citric acid monohydrate; or
 comprises:   10 μg DNA and 0.25 mg PLG;   100 μg DNA and 2.5 mg PLG;   10 μg DNA and 9.25 mg PLG; or   100 μg DNA and 2.5 mg PLG.   
   
   
       24 . The immunogenic composition of  claim 8 , wherein the HIV Gag DNA immunogenic composition component is an aqueous solution comprising 50.0 mg/ml PLG, 2.0 mg/ml plasmid DNA, 0.5 mg/ml hexadecyltrimethylammonium bromide, 44 mg/ml mannitol, 14.7 mg/ml sucrose, 0.37 mg/ml EDTA, 1.4 mg/ml sodium citrate dihydrate, and 0.04 mg/ml citric acid monohydrate; or comprises:
 10 μg DNA and 0.25 mg PLG;   100 μg DNA and 2.5 mg PLG;   10 μg DNA and 9.25 mg PLG; or   100 μg DNA and 2.5 mg PLG.   
   
   
       25 . The immunogenic composition of  claim 8 , wherein the concentration of o-gp140 is between about 0.1 and 10 mg/mL. 
   
   
       26 . The immunogenic composition of  claim 8 , wherein the concentration of o-gp140 per dose is approximately 100 μg/dose. 
   
   
       27 . The immunogenic composition of  claim 8 , wherein the HIV immunogenic composition component contains:
 0.4 mg/ml o-gp140, 2.75 mg/ml sodium citrate dihydrate, 0.15 mg/ml citric acid monohydrate, 17.53 mg/ml sodium chloride;   2 mg Env-DNA/ml, 50 mg PLG/ml, and 2 mg Gag-DNA/ml; or   0.4 mg/ml Env protein and MF59.   
   
   
       28 . The immunogenic composition of  claim 8 , wherein the HIV protein immunogenic composition component further comprises an adjuvant. 
   
   
       29 . The immunogenic composition of  claim 28 , wherein the adjuvant is MF59 or CpG. 
   
   
       30 . The immunogenic composition of  claim 29 , wherein the adjuvant is MF59 and MF59 comprises 39 mg/ml squalene, 4.7 mg/ml polysorbate 80, 4.7 mg/ml sorbitan trioleate 2.68 mg/ml sodium citrate dihydrate, 0.17 mg/ml citric acid monohydrate. 
   
   
       31 . The method of  claim 10 , wherein at least one administration is intramuscular or intradermal. 
   
   
       32 . An HIV immunogenic composition comprising a nucleic acid expression vector comprising at least one HIV Gag- or Env-encoding sequence; and PLG.