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 | ||
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 | ||
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] |