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Table 2 HIV-antigen specific therapeutic vaccinations

From: Can immunotherapy be useful as a “functional cure” for infection with Human Immunodeficiency Virus-1?

a) Non dendritic cell-based
Name Trial Species Baseline patients characteristics Type of immune therapy Route and frequency of administration Number of patients Outcome References
Uncontrolled clinical trial Human Therapy naïve Remune® iv 2527 Increased HIV-specific T cell responses. Positive impact on controlling the virus. [78]
P2101B (thai open label trial) Human Therapy naïve Remune® iv every 12 weeks for 132 weeks 223 Increasing CD4 and CD8 T cell counts and stable viral load. [79]
Randomized double blind placebo controlled trial Human HAART ALVAC, ALVAC + Remune, placebo iv injections Alvac @w 8, 12, 16, 20. Remune@w 0, 4, 12, 20 79 Safe and immunogenic. No difference between the three groups after STI on viral rebound. [80]
Placebo controlled Indian rhesus macaque Chronic SIV HAART SIV mac239 gag and env DNA vaccine im 3 injections 23 Increase in HIV specific cellular responses and lower viral rebound in vaccinated animals. [81]
  Indian rhesus macaque Chronic SIV HAART SIV mac239 gag and env DNA vaccine + IL-15 In vivo electroporation 3 Sustained polyfunctional T cells. One log decrease in VL. [82]
  Human HAART DNA vaccine consisting of CTL epitopes im injections w 0, 4, 8, 16 41 Safe and tolerable. In some persons weak responses. Overall no differences with placebo group. [83]
VRC HIV DNA 009-00-VP double blind placebo controlled Human HAART plasmid DNA encoding subtype B Gag-Pol-Nef and multiclade env im injections w 0, 4, 8, 24 20 Poorly immunogenic. No effect on viral rebound after ATI. [84]
  Human HAART Plasmid DNA multiclade Patch 12 Broader and higher HIV specific T-cell responses. No effect on viral rebound after ATI. [85]
ANRS 094 single arm open Human   ALVAC vCP1433 im injections w 0, 4, 8, 12 50 Safe and immunogenic. Delay in treatment resumption of ATI. [86]
ANRS 093 human HAART ALVAC + lipo 6T 4 injections followed by 3 cycles sc IL2 im injections of ALVAC w 0, 4, 8, 12. IL-2@w 16, 24, 32 71 Lower viral set point after ATI, correlated with HIV specific CD4 T cell responses. [87]
ACTG (A5024) randomized partially blinded phase II Human HAART ALVAC ALVAC + sc IL2 sc IL2 alone placebo im injections of ALVAC w 0, 4, 8, 12. IL-2 sc for5 days in 8 week cycles 19 Lower viral rebound after ATI in ALVAC vaccines. IL-2 + vaccine boosted CD4 T cell count but had no influence on VL. [88]
Double blind placebo controlled Human HAART (acute phase) ALVAC ALVAC + Remune iv injection of ALVAC w8, 12, 16, 20. remune w 0, 4, 12, 20 79 No influence on VL after ATI. Increased CD4 and CD8 T cell responses [80]
CTN173 randomized controlled Human HAART ALVAC, ALVAC + remune, placebo im injections of ALVAC w8, 12, 16, 20. Remune w0, 12, 20. ATI w24 52 No lower viral setpoint. Tendency towards delay of rebound [89]
ORVACS Human HAART ALVAC vcp1420 placebo im injections w 0, 4, 8, 20 65 Higher viral rebound in vaccines [90]
  Human HAART Fowlpox gag/pol (PC) 3 im injections (w 0,4, 12). ATI w20 35 Lower man viral rebound in FC group and this is associated with IgG2 antibodies to HIVp24 [91][92]
Fowlpox gag/pol IFN-y (FC
placebo
  Indian rhesus macaque Chronic SIV HAART MVA gag pol and MVA env im injections w10, 16. STI w20 18 Tendency lower viral rebound after ATI but not significant. [93]
  Rhesus macaque Chronic SIV HAART MVA + Ad5 gag and env im injection of Ad5/35 on day 74 and MVA-SIV on day 134   Vaccinated animals had higher CD4 T cell counts, SIV-specific cell-mediated immunity and anti-SIV-neutralizing antibodies. After ATI there was a sustained reduction in VL and increased CD4 T cell responses. [94]
  Human HAART MVA nef sc injections w 0, 4, 16. ATI w 18 14 Well tolerated. Induction HIV specific responses. Lower viral rebound. [95]
  Human HAART MVA clade A p24/17 + CD8 T cell epitopes id 4 week interval 18 Amplification and broadening of CD8 and CD4 T cell responses. Induction of CD8 T cell responses with capacity to inhibit viral replication in vitro [96][97]
  Indian rhesus macaque Chronic SIV HAART Ad5 and Ad35 SIV gag, env, nef + IL15 im injections 15 Increased T cell responses no effect on viral rebound. [98]
w 16, 22, 36, 42
  Human HAART rAd5 gag im injections 114 Safe and well tolerated. 0.5 log lower VL 16 weeks after A-STI [99]
w 0, 4, 26.
ATI w 38 to 54
b) Dendritic cell-based
Species Number and baseline characteristics Loading strategy Antigen Results References
Human 6 therapy- naïeve Pulsing Recombinant HIV-1 MN gp160 or synthetic peptides corresponding to HLA-A2- restricted cytotoxic epitopes of envelope, Gag, and Pol proteins Well tolerated and no effect on viral load. HIV specific responses were enhanced. [100]
Human 4 HAART Pulsing Seven CTL peptides with HLA-A*2402 restriction Well tolerated, discontinuation of HAART after vaccination failed to lower viral set points. CD8 T cell responses induced in 2 out of 4 patients. [101]
Pigtail macaque 36 HAART Pulsing of whole blood Gag proteins or peptides spanning all 9 SIV proteins SIV-specific CD4 and CD8T cell responses during antiretroviral cover and off treatment. Virus levels were 10-fold lower in immunized animals for 1 year. [102]
Chinese rhesus macaques HAART Pulsing AT-2 inactivated virus Effective and durable SIV-specific cellular and humoral immunity is elicited. At week 34 of the study: 50-fold decrease of SIV DNA and a 1,000-fold decrease of SIV RNA. [103]
Human 18 therapy naieve Pulsing AT-2-inactivated virus Plasma viral load levels were decreased by 80% (median) over the first 112 days following immunization. The suppression of viral load was positively correlated with HIV-1-specific interleukin-2 or IFN-γ expressing CD4 T cells and with HIV-1 gag-specific perforin-expressing CD8 effector cells. [104]
Human 12 HAART Pulsing Heat-inactivated virus Safe and well tolerated. Partial viral control 24 weeks after ATI . [105]
Human 24 therapy- naïeve Pulsing Heat-inactivated virus Feasible, safe and well tolerated. Modest decrease in viral load 24 weeks after first vaccination compared to controls. [106]
Human 29 HAART Live virus ALVACvcp1452 Viral load rebounded in both groups no differences in HIV-specific immune responses. [107]
    ALVACvcp1452 + KLH     
    KLH     
Human 9 HAART Electroporation Autologous mRNA encoding Gag, Vpr, Rev and Nef Mild adverse events. Full or partial HIV-specific immune responses in 7/9 subjects. [108]
Human 9 HAART Electroporation Autologous mRNA encoding Gag, Vpr, Rev and Nef Partial viral control . [109]
Human 17 HAART Electroporation mRNA encoding tat rev nef Vaccine was safe, 69 weeks after STI 6/17 patients remains off therapy. [110]
Human 6 HAART Electroporation mRNA encoding gag and mRNA encoding tat rev nef Vaccine was safe. HIV-specific responses against Gag were broader, higher and polyfunctional after vaccination. CD8 T-cells could inhibit superinfection of CD4 T-cells. [111]
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