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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]