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Updated, Annotated Preventive Vaccine Pipeline Table

Information On the Current Preventive HIV Vaccine Pipeline, Annotated With Commentary and Links to Published and Presented Data

May 29, 2008

Preventive HIV Vaccines
ALVAC vCP1521Canarypox vector encoding: HIV-1 CRF01_AE env, clade B gag, the protease- encoding portion of the pol gene and a synthetic polypeptide encompassing several known CD8 T- cell epitopes from the Nef and Pol proteinsSanofi PasteurPhase III
Phase I (in infants)
• Results of USMHRP/Thai phase III trial anticipated in 2009, efficacy considered highly unlikely
Published immunogenicity data showed CD8 responses in only 25% of recipients (although this response was so poor that it was not significantly different from placebo recipients) and Env- specific CD4 responses in 84%. Antibody responses only neutralized laboratory HIV strains.
Published evidence of protective efficacy in infant macaques exposed to SIV via oral exposure to infected milk (to mimic breastfeeding) led to the infant safety trial, preliminary data was presented at the AIDS Vaccine 2007 conference, Late Breakers abstract number P06-48
AIDSVAX B/E (booster only)Recombinant gp120 envelope proteinVaxGenPhase III• Failed to protect against HIV infection in two large efficacy trials, one primarily based in North America, the other in Thailand
• Being used as a booster in the USMHRP/Thai efficacy trial
• The manufacturer, VaxGen, has laid off 70% of their staff and may be on the brink of closure (as of May 2008)
MRKAd5Adenovirus serotype 5 vector containing gag/pol/nef genes from HIV-1 clade BMerckPhase IIb (HVTN 503, HVTN 502/Merck 023)• Trial stopped after interim safety/efficacy analysis by the DSMB on September 18, 2007
• Failed to protect against acquisition or reduce post- infection viral load, enhanced susceptibility in a subset of participants with pre- existing antibody responses to the Ad5 vector see TAGLine article for more information
• Safety and immunogenicity data from phase I studies has been published in Clinical Infectious Diseases online
VRC- HIVDNA016- 00- VP
VRC- HIVADV014- 00- VP
Prime: Six separate DNA plasmids containing gag, pol, and nef genes from HIV-1 clade B, and env genes from clades A, B, and C
Boost: Adenovirus serotype 5 vectors containing gag/pol genes from HIV-1 clade B and env genes from clades A, B, and C
NIH Vaccine Research Center/ GenVec/ VicalPhase IIb (PAVE 100)• On hold due to Merck vaccine failure, being redesigned as a "discovery" trial in MSM (men who have sex with men) who are do not have antibodies against Ad5
• Safety concerns in people with pre-existing immunity to Ad5 (as measured by anti-Ad5 antibodies) will almost certainly preclude further development of Ad5-based HIV vaccines
• Decision on PAVE100 trial to be discussed at a special meeting of the NIAID AIDS Vaccine Research Subcommittee on May 30
• Data from separate phase I studies of the prototype DNA and Ad5 vectors were published in the December 15, 2006 issue of the Journal of Infectious Diseases. Data on the immunogenicity of the prime- boost (DNA+Ad5) approach can be found in the abstracts from the AIDS Vaccine 2007 conference, Late Breakers abstract numbers P06-43, P06-44, P06-47; Oral Sessions, abstract numbers OA08-01, OA08-03, OA08-04; Poster Sessions abstract numbers P06-16, P06-19, & P06-20
• The data indicate that the majority of recipients (∼70% in the largest prime-boost studies) develop HIV-specific T cell responses in response to the vaccine and other presentations suggest that these responses have a more "polyfunctional" profile than those induced by Merck's vaccine
• Very little data on the breadth of the vaccine- induced T cell response has been reported, number of epitopes targeted not yet known
pGA2/JS7 DNA MVA/HIV62DNA prime and MVA booster vaccines encoding gag, pol and env from HIV-1 clade BNIAID, GeovaxPhase IIA• Immunogenicity data reported at CROI 2008 (see the first presentation in the Tuesday webcast of the vaccine session) was not impressive
• From the IAVI Report: "After the second MVA injection at the lower dose, 87% of participants were considered responders based on their CD4+ T-cell responses to any of the HIV immunogens included in the candidates. After the second MVA injection at the higher dose, 77% of participants mounted CD4+ T-cell responses to any of the included HIV immunogens.
• Overall the CD8+ T-cell responses were much lower. At the higher dose, 42% of participants were considered responders, compared to 33% in the low-dose group"
• No data on the breadth of the responses has yet been presented
ISS P-001Recombinant Tat protein from HIV-1 clade BISS, ExcellPhase IIA• The development of this vaccine has been mired in controversy, with recent news reports indicating rifts between the main developer Barbara Ensoli and her former colleague Fernando Aiuti that have led to litigation
• A review from November 2006 describes the development process but does not report on immunogenicity (these manuscripts are said to be in preparation but remain unpublished as of May 2008)
LIPO-55 lipopeptides containing CTL epitopes (from Gag, Pol and Nef proteins)ANRS; AventisPhase II • Preliminary data presented by Larry Corey at CROI 2006 (see Monday webcast, last session of the day) indicated only 3 out of 77 recipients of ALVAC+ LIPO-5 developed detectable CD8 T cell responses, further development appears unlikely
HIVIS 03 DNA-MVA prime- boost HIV-1 vaccine candidate Prime: HIVIS DNA encoding env (A,B,C), gag (A,B), RT (B), rev (B)
Boost: MVA-CMDR encoding env (E), gag (A), pol (E)
Karolinska Institute, SMI, Vecura, USMHRPPhase I/II• A detailed Powerpoint presentation of the phase I data is available on the HIV Vaccine Enterprise website
• In a 38-person phase I trial, responses to both Env and Gag reported in 58%, IL-2- producing T cells in 68%, proliferative responses in 92%
• Breadth of response in terms of number of epitopes targeted is not reported
GTU- Multi- HIV DNA vaccine containing nef, rev, tat, gag, pol, env, and CTL epitopesFIT BiotechPhase I/II• Vaccine contains multiple antigens, designed specifically to cover variability of HIV clades
• Company seeking partners to continue development
• No phase I immunogenicity data from HIV- negative recipients has been publicly presented yet
• The company's presentation of data from a phase I therapeutic study in South Africa are available on the HIV Vaccine Enterprise website
DNA-C + NYVAC-CPrime: DNA vaccine encoding clade C env, gag, pol, nef
Boost: NYVAC-C attenuated vaccinia vector encoding clade C env, gag, pol, nef
EuroVacc Foundation/
Phase I/II• Phase I trial data published in the Journal of Experimental Medcine. While the vaccine- encoded HIV env protein induced T cell responses in most recipients, only 48% developed responses to Gag, Pol or Nef (to quote from the paper: "The responses against Gag, Pol, and Nef were generally transient and substantially lower in magnitude compared with the env- specific responses.")
DNA vaccine + fowlpox boost containing gag, rev, tat, vpu, and truncated env genes from HIV-1 clade A/EUniversity of New South Wales, AustraliaPhase I• Fowlpox vector showed disappointing immunogenicity in a phase I therapeutic trial, results published in Human Vaccines (full text of the paper is available, with the company's spin, on the Virax website)
• The University of New South Wales is conducting a small phase I trial of clade A/E constructs in uninfected volunteers in Thailand, Virax is no longer involved
ADMVAMVA vector containing env/ gag - pol, and nef-tat genes from HIV-1 clade CAaron Diamond AIDS Research Center (ADARC), IAVI, IDTPhase I• Includes additional antigens compared to Merck's vaccine, (Env and Tat), preliminary immunogenicity data presented at AIDS Vaccine 2007 conference, Oral Sessions abstract number OA02-01
• After three immunizations (months 0, 1 & 6) 8/13 recipients of the highest dose developed T cell responses to "any antigen"
• Intended for use as a booster after administration of a DNA vaccine, prime-boost data not yet presented
GSK Protein HIV VaccineRecombinant Tat, Nef, and gp120 proteins in ASO2A adjuvantGlaxoSmith- KlinePhase I• Vaccine does not include HIV's Gag protein which is a critical target for T cell responses, further development unlikely
AdVax 101 (VEE)Venezuelan Equine Encephalitis virus vector containing the gag gene from HIV-1 clade CAlphaVaxPhase I• Preliminary data presented by Larry Corey at CROI 2006 (see Monday webcast, last session of the day) indicated 0 out of 35 recipients developed detectable CD8 T cell responses, further development appears unlikely
TBC-M358 (MVA)
TBC-M335 (MVA)
TBC-F357 (FPV)
TBC-F349 (FPV)
MVA and fowlpox vectors encoding env, gag, tat, rev, nef, and reverse transcriptase genes from HIV-1 clade BNIAID, TherionPhase I• Contains additional antigens compared to Merck's vaccine (Env, Tat & Rev)
• Preliminary immunogenicity data presented at the AIDS Vaccines 2007 conference, abstract number OA02-02
• Results of the small phase I study showed CD8 T cell responses in around half the recipients
LIPO-4T (LPHIV-1)4 lipopeptides containing CTL epitopes (from gag, pol-RT, pol, and nef)ANRS, Biovector SAPhase I• Most recent data, published in PLoS One, is not very encouraging, maximum percentage of responders in terms of CD8 T cell responses was 52% but very few participants responded to more than one epitope
LFn-p24Anthrax- derived polypeptide LFn Gag p24 proteinAVANT, NIAID, WRAIRPhase I• Immunogenicity results from this study were reported at AIDS Vaccines 2007, Poster Sessions, abstract number P06-13
• CD8 T cell responses are reported in 5/12 recipients of various doses, CD4 responses in 12/12
• No data on breadth or function presented
HIV CTL MEP + RC529-SE and GM-CSF adjuvantsDNA vaccine containing CTL epitopes from env or gagNIAID, WyethPhase I• Preliminary data presented by Larry Corey at CROI 2006 (see Monday webcast, last session of the day) indicated 0 out of 65 recipients developed detectable T cell responses
DNA + Protein Vaccine CombinationDNA vaccine containing a gag gene (from HIV-1 clade C) and 5 env genes (from clades A, C, & E + two from clade B), plus a protein boost using recombinant gp120 proteins from the same 5 isolates that supplied the env genes for the DNA componentUniversity of Mass. Medical School, Advanced BioScience Laboratories, Inc.Phase I• Based on the idea that multiple Envs from different clades of HIV stand a better chance of inducing neutralizing antibodies
Some limited evidence of neutralization reported but only against some HIV variants, several viruses tested were completely resistant the antibodies induced by the vaccine
tgAAC09 AAVAdeno- Associated virus vector containing gag, protease, and reverse transcriptase genes from HIV-1 clade CTargeted Genetics, IAVIPhase II• No longer in development due to poor immunogenicity in humans (<20% of recipients developed an HIV- specific CD8 T cell response)
Recent reports suggest the possibility that the vector was not effective because many people have pre- existing AAV- specific CD8 T cell responses
ADVAX DNADNA vaccine containing gag, env, pol, nef, and tat genes from HIV-1 clade CIAVI, ADARC, VicalPhase I • Designed as a priming immunization to be followed by ADARC's MVA vector (see above)
• Includes additional antigens compared to Merck's vaccine, (Env and Tat) but immunogenicity data not yet publicly presented
VRC- HIVDNA- 009- 00- VPDNA vaccine containing gag, pol, and nef genes from HIV-1 clade B, and env genes from clades A, B, and C, together with an adjuvant gene encoding an IL-2 fusion proteinVRC, HVTN, VicalPhase I• Results presented at AIDS Vaccines 2007, Oral Sessions, abstract number OA08-07
• Construct induced IL-2- and interferon- gamma- producing T cells in most participants, but best results (in terms of both % responders and magnitude of the response) were obtained with the highest adjuvant dose given two days after the DNA vaccine
• There was an unusually high drop- out rate (only 49/70 received all four doses), which is not explained in the abstract (only one adverse event, malaise, was reported)
PolyEnv1Vaccinia viruses expressing 23 different env genesSt. Jude Children's Research HospitalPhase I• Limited data available, rationale for the approach outlined in a recent review in Frontiers in Bioscience
EnvDNADNA vaccine encoding multiple env genesSt. Jude Children's Research HospitalPhase I• A short "research letter" describing results of a phase I study of a prototype construct carrying a single Env protein was recently publishing in the journal AIDS
• Non- neutralzing antibodies were induced in all recipients
EP HIV-1090 DNA EP-1043DNA vaccine containing 21 CTL epitopes from gag, pol, env, nef, rev, and vpr (HIV-1 clade B) + recombinant protein vaccine including 18 conserved CD4 T-cell epitopes from the Env, Gag, Pol, and Vpu proteinsNIAID, Pharmexa (formerly Epimmune)Phase I• Preliminary immunogenicity data presented at November 2007 HVTN meeting, data do not appear to be online but a company press release suggests that the majority of recipients of the protein vaccine developed CD4 T cell responses while, reading between the lines, CD8 T cell responses to the DNA vaccine were poor
• This interpretation is supported by preliminary data on the DNA vaccine presented by Larry Corey at CROI 2006 (see Monday webcast, last session of the day) which indicated that 1 out of 26 recipients developed a detectable T cell response
HIV DNA vaccine + IL-12DNA vaccines encoding HIV-1 clade B gag and IL-12NIAID, WyethPhase I• Data reported at AIDS Vaccines 2007 on both this vaccine and the one below including IL-15, Poster Sessions, abstract number P06-11
• From the abstract: "A 3-injection regimen of p37 gag+IL-12 DNA vaccine has shown minimal immunogenicity, whereas gag DNA alone and gag+IL-15 DNA vaccines have shown none"
HIV DNA vaccine + IL-15DNA vaccines encoding HIV-1 clade B gag and IL-15NIAID, WyethPhase ISee above
Soluble subunit protein
Oral vaccine utilizing salmonella typhi encoding gp120-CD4, subunit protein vaccine containing the same gp120-CD4 proteinInstitute of Human VirologyPhase I• Designed with the aim of inducing mucosal responses
Trial still not opened according to
• According to a recent review by the developer, George Lewis, the putative promise of this approach "remains largely unrealized at the level of human clinical trials"
SAAVI DNA-C2DNA plasmids (clade C Gag, RT, Tat, Nef; clade C Env) + MVA vector (clade C Gag, RT, Tat, Nef; clade C gp150CT)South African AIDS Vaccine Initiative (SAAVI), Therion Phase I• No data yet presented
C86P1HIV gp140 V2 loop deleted protein and LTK63 adjuvant delivered intranasally followed by HIV gp140 V2 loop deleted protein + MF59 adjuvant delivered intramuscularlyNovartis Phase I• Trial ongoing, no results yet presented
• Results from a phase I trial using the same antigen, which was designed to improve the potential for inducing neutralizng antibodies, reported no significant breadth of neutralization against a panel of clade B HIV isolates. Further development is unlikely
• These results were presented at AIDS Vaccines 2007, Poster Sessions, abstract number P06-12
VICHREPOLChimeric recombinant protein comprised of C-terminal p17, full p24, and immunoreactive fragment of gp41 with polyoxidonium adjuvantMoscow Institute of Immunology, Russian Federation Ministry of Education and SciencePhase I• Data presented at the International Conference on AIDS in 2006 indicated that the vaccine is safe, immunogenicity data doesn't appear to have been presented yet
ALVAC vCP205ALVAC-HIV vCP205 env, gag, pol (B) (vCP205, HIV-1 env/gag/pol) administered subcutaneously via ex vivo transfected, autologous dendritic cells (intradermally or intramuscularly)US Military HIV Research Program/Sanofi PasteurPhase I• Detailed data presentation from AIDS Vaccines 2007 conference available on the Global HIV/AIDS Vaccine Enterprise website
• Approach induced T cell responses in 3/7 volunteers
• Results may suggest ways to improve dendritic cell- based approaches but this specific strategy is not being developed further
VRC- HIVADV027- 00- VPAdenovirus serotype 35 vector containing an env gene from clade ANIH Vaccine Research Center/ GenVecPhase I• No data yet presented
Ad26.ENVA.01Adenovirus serotype 26 vector containing an env gene from clade ACrucell, National Institutes for Allergy & Infectious Diseases (NIAID)Phase I• No data yet presented

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This article was provided by Treatment Action Group.
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