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 HIV DNA vaccine composition comprising 
 a nucleic acid expression vector comprising at least one HIV Gag- or Env-encoding sequence; and    PLG.    
   
   
       2 . The vaccine composition of  claim 1 , wherein the concentration of PLG is between about 5 and 100 fold greater than the concentration of the nucleic acid expression vector.  
   
   
       3 . The vaccine composition of  claim 2 , 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.  
   
   
       4 . The vaccine composition of  claim 1 , wherein the nucleic acid concentration per dose is between approximately 1 μg/dose and 5 mg/dose and the PLG concentration per dose is between approximately 10 μg/dose and 100 mg/dose.  
   
   
       5 . The vaccine composition of  claim 1 , as set forth in Table 1 or Table 2.  
   
   
       6 . The vaccine composition of  claim 1 , as set forth in column 2 of Table 9.  
   
   
       7 . An HIV vaccine composition comprising 
 oligomeric gp140 (o-gp140); and    a pharmaceutically acceptable excipient.    
   
   
       8 . The HIV vaccine of  claim 7 , wherein the concentration of o-gp140 is between about 0.1 and 10 mg/mL.  
   
   
       9 . The HIV vaccine of  claim 7 , wherein the concentration of o-gp140 per dose is approximately 100 μg/dose.  
   
   
       10 . The HIV vaccine of  claim 7 , as set forth in Table 3 or Table 11.  
   
   
       11 . The HIV vaccine of  claim 7 , further comprising an adjuvant.  
   
   
       12 . The HIV vaccine of  claim 11 , wherein the adjuvant is MF59 or CpG.  
   
   
       13 . The HIV vaccine of  claim 12 , wherein the adjuvant is MF59 and MF59 is as set forth in Table 4.  
   
   
       14 . An HIV vaccine comprising an HIV Env DNA vaccine composition, said HIV Env DNA vaccine composition comprising at least one HIV Env-encoding sequence and PLG; an HIV Gag DNA vaccine composition, said HIV Gag DNA vaccine composition comprising at least one HIV Gag-encoding sequence and PLG; and an HIV vaccine composition, said HIV vaccine composition comprising oligomeric gp140 (o-gp140) and a pharmaceutically acceptable excipient  
   
   
       15 . A method of generating an immune response in a subject, said method comprising: 
 (a) administering to the subject at least one HIV vaccine composition, said composition comprising: (i) a nucleic acid expression vector comprising at least one HIV Gag- or Env-encoding sequence or (ii) an HIV oligomeric gp 140; and    (b) administering to the subject, at a time subsequent to the administering of step (a), at least one HIV vaccine composition, said composition comprising: (i) a nucleic acid expression vector comprising at least one HIV Gag- or Env-encoding sequence or (ii) an HIV oligomeric up 140.    
   
   
       16 . A method of generating an immune response in a subject, said method comprising: (a) administering to said subject at least one HIV DNA vaccine 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 vaccine composition comprising HIV oligomeric gp140.  
   
   
       17 . The method of  claim 16 , wherein step (a) comprises multiple administrations of said at least one HIV DNA vaccine composition and step (b) comprises multiple administrations of said at least one vaccine composition comprising HIV oligomeric gp 140.  
   
   
       18 . The method of  claim 17 , 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.  
   
   
       19 . The method  claim 16 , wherein step (a) comprises administering at least one HIV Gag DNA vaccine and at least one HIV Env DNA vaccine.  
   
   
       20 . The method of  claim 15  wherein step (b) comprises concurrently administering at least one DNA vaccine comprising a nucleic acid expression vector comprising at least one HIV Gag- or Env-encoding sequence and at least one HIV vaccine comprising oligomeric gp 140.  
   
   
       21 . The method of  claim 20 , wherein step (a) comprises administering at least one HIV Gag DNA vaccine and at least one HIV Env DNA vaccine.  
   
   
       22 . The method of  claim 15 , wherein at least one administration is intramuscular or intradermal.  
   
   
       23 . 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 oligomeric gp140 (o-gp140) protein from the host cell.    
   
   
       24 . The method of  claim 23 , wherein the o-gp140 is secreted from the cell and isolated from the cell supernatant.  
   
   
       25 . A method of making an HIV DNA vaccine according to  claim 1 , comprising the step of 
 combining a nucleic acid expression vector comprising a sequence encoding one or more HIV polypeptides with aseptic PLG microparticles such that the nucleic acid binds to the PLG microparticles to form a DNA/PLG HIV vaccine.    
   
   
       26 . The method of  claim 25 , further comprising the step of lyophilizing the DNA/PLG HIV vaccines.  
   
   
       27 . A method of making an HIV vaccine according  claim 7 , comprising combining o-gp140 with an adjuvant.  
   
   
       28 . The HIV vaccine of  claim 14 , wherein the concentration of PLG is between about 5 and 100 fold greater than the concentration of the nucleic acid expression vector.  
   
   
       29 . The HIV vaccine of  claim 28 , 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.  
   
   
       30 . The HIV vaccine of  claim 14 , 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.  
   
   
       31 . The HIV vaccine of  claim 14 , wherein the HIV Env DNA vaccine composition component is as set forth in Table 1 or column 2 of Table 9.  
   
   
       32 . The HIV vaccine of  claim 14 , wherein the HIV Gag DNA vaccine composition component is as set forth in Table 2 or column 2 of Table 9.  
   
   
       33 . The HIV vaccine of  claim 14 , wherein the concentration of o-gp140 is between about 0.1 and 10 mg/mL.  
   
   
       34 . The HIV vaccine of  claim 14 , wherein the concentration of o-gp140 per dose is approximately 100 μg/dose.  
   
   
       35 . The HIV vaccine of  claim 14 , wherein the HIV vaccine composition component is as set forth in Table 3 or Table 11.  
   
   
       36 . The HIV vaccine of  claim 14 , wherein the HIV vaccine composition component further comprising an adjuvant.  
   
   
       37 . The HIV vaccine of  claim 36 , wherein the adjuvant is MF59 or CpG.  
   
   
       38 . The HIV vaccine of  claim 37 , wherein the adjuvant is MF59 and MF59 is as set forth in Table 4.  
   
   
       39 . The method of  claim 16 , wherein at least one administration is intramuscular or intradermal.