Table 1.
Representative clinical studies.
| Study name and phase | Immunogen | Vectors, regimen and route of immunization | Immune responses generated | References |
|---|---|---|---|---|
| (I) HETEROLOGOUS PRIME-BOOST STUDIES | ||||
| HIVCORE002 (Phase I study) | HIVconsv (T cell immunogen based on conserved regions) | ChAdV63/MVA (i.m.) | -CD4+ and CD8+ T cells -In vitro virus inhibition | Borthwick et al., 2014 |
| DNA/ChAdV63/MVA (i.m.) | ||||
| DNA/MVA/ChAdV63 (i.m.) | ||||
| HVTN 505 (Phase IIb study) | VRC-HIVDNA016-00-VP/VRC-HIVADV014-00-VP | DNA-prime (i.m. biojector device)/rAd5 boost (i.m. needle and syringe) | -T cells and gp140 binding IgG antibodies | Hammer et al., 2013 |
| HVTN 503/Phambili (Phase IIb study) | MRKAd5 HIV-1 Gag/Pol/Nef | DNA-prime (i.m.)/Ad5 boost (i.m.) | -CD8+ and CD4+ T cells | Gray et al., 2011 |
| Phase 1 study | Gag and Env DNA and recombinant trimeric Env glycoprotein | DNA-prime (i.m.)/Protein boost with MF59 adjuvant | -Robust B and T cells | Spearman et al., 2011 |
| -Strong NAbs to SF162 | ||||
| -ADCC and neutralization of tier 2 strains | ||||
| Phase I/II study | Multi-clade, multigene: DNA/HIV-1 gp160, p17/p24 Gag and MVA/HIV-1 Gag/Pol | Low dose (i.d.) DNA-prime (x3)/MVA-boost (i.m. x2) | -High magnitude and broad CD4+ and CD8+ T cell responses | Bakari et al., 2011 |
| (DDDMM) | -Env antibodies | |||
| Phase I study DP6-001 | Multigene polyvalent gp120 and Gag DNA and polyvalent gp120 protein | i.m. or i.d. Polyvalent DNA-prime/i.m. protein-boost (with QS21 adjuvant) | -High titer binding and BNAbs, ADCC and multifunctional T cells | Bansal et al., 2008; Vaine et al., 2010 |
| RV144 (Phase III study) | ALVAC-HIV vCP1521/AIDSVAX gp120 B/E | ALVAC-prime (i.m.)/gp120 protein-boost | -T cells and non-neutralizing antibodies to V1/V2 loop | Rerks-Ngarm et al., 2009 |
| Phase I study | Multigenic HIV DNA (gp160- A/B/C; Rev B, Gag A/B and RT- B and HIV-MVA Env/Gag/Pol) | DNA- prime (i.d. with Biojector)/MVA-boost (i.d./i.m.); with or without GM-CSF adjuvant | -Broad and potent cellular immune responses | Sandstrom et al., 2008; Gudmundsdotter et al., 2009 |
| HVTN 502/STEP Study (Phase IIb) | MRKAd5 HIV-1 Gag/Pol/Nef | DNA-prime (i.m.)/Ad5 boost (i.m.) | -Strong CD8+ T cell responses | Buchbinder et al., 2008; McElrath et al., 2008 |
| Phase 1 study | HIVA (HIV-1 clade A and a CTL epitope string) | DNA-prime (i.m.)/MVA-boost (i.m.) | -Multifunctional CD4+ and CD8+ T cells | Mwau et al., 2004; Goonetilleke et al., 2006 |
| Phase I study (EuroVacc: EV02) | HIV-1 clade C-Env/Gag/Pol/Nef (DNA-C and NYVAC-C) | DNA-prime (i.m.)/NYVAC- boost (i.m.) | -Durable, broad and poly-functional CD4+ and CD8+ T cells | Harari et al., 2008; McCormack et al., 2008 |
| Phase I study | ALVAC-HIV(vCP300) | ALVAC-prime (i.m.)/i.m. Protein-boost (with MF59 adjuvant) | -Durable CTLs | Evans et al., 1999 |
| gp120/gp41, Gag, Pro, Nef, Pol and SF-2 rgp120 | -Antibody responses | |||
| Phase I study | ALVAC-HIV(vCP205) | ALVAC-prime (i.m.)/i.m. Protein-boost (with MF59 adjuvant) | -Strong CD8+ T cell responses and NAbs | Belshe et al., 1998 |
| gp120/gp41, Gag, Pol and SF-2 rgp120 | ||||
| (II) HOMOLOGOUS PRIME-BOOST OR SINGLE DOSE STUDIES | ||||
| HVTN-070 and -080 Phase I studies | PV (PENNVAX(R)-B DNA expressing Gag, Pol, Env and DNA/IL-12 | DNA+IL-12 (i.m. or by electroporation) | -CD4+ and CD8+ T cell responses | Kalams et al., 2013 |
| IPCAVD-001 | Ad26.ENVA.01 | Intramuscular delivery of rAd26 | -Binding antibodies | Baden et al., 2013; Barouch et al., 2013 |
| -Multiple CD8+ and CD4+ T cell responses | ||||
| -ADCC and virus inhibition | ||||
| HVTN 090 Phase Ia study | VSVINN4CT1Gag1 (recombinant VSV expressing HIV-1 Gag) | Dose-escalating i.m. delivery | Low level T cell responses detected following initial dosing | Fuchs et al., 2012, 2013 |
| Phase I study | Ad35-GRIN (Gag, RT, Integrase, Nef) and Ad35-GRIN/ENV | Intramuscular delivery of Ad35-GRIN/Env or Ad35-GRIN | -Robust, broad and polyfunctional CD4 and CD8+ T cells | Keefer et al., 2012 |
| Phase I/II study (RISVAC02) | MVA-B (monomeric gp120 and clade B Gag/Pol/Nef poly-protein) | Three doses of MVA (i.m.) | -Durable antibody and cellular immune responses | Garcia et al., 2011; Gomez et al., 2011 |
| Phase I study | ADVAX (multigenic HIV-1 DNA vaccine) | DNA by i.m. electroporation | -CD4 and CD8+ T cells with multiple cytokines | Vasan et al., 2011 |
| VAX 003 (Phase III study) | Bivalent recombinant gp120 vaccine: AIDSVAX B/E | Seven i.m. injections; with Alum adjuvant | -Binding and neutralizing antibodies to gp120 | Pitisuttithum et al., 2006 |
| VAX 004 (Multicentre Phase III study) | Bivalent recombinant gp120 vaccine: AIDSVAX B/B | Seven i.m. injections; with Alum adjuvant | -Binding and neutralizing antibodies to gp120 | Flynn et al., 2005; Gilbert et al., 2005 |
i.m., intramuscular; i.n., intranasal; i.d., intradermal; s.c., subcutaneous; i.p., intraperitoneal; ADCC, antibody dependent cytotoxicity; NAbs, neutralizing antibodies; BNAbs, broadly neutralizing antibodies.