Drugs

LIPO-5

Other Names: ANRS HIV-LIPO-5, HIV-LIPO-5 Drug Class: Therapeutic Vaccines Organization: French National Agency for Research on AIDS and Viral Hepatitis (ANRS) Phase of Development: LIPO-5 is in Phase II development as a therapeutic HIV vaccine. (LIPO-5 is also being studied as a preventive HIV vaccine.)

(Compound details obtained from ANRS: HIV Vaccine Research Programme,1 AIDS article,2 and Treatment Action Group website3)

Pharmacology


Mechanism of Action: Therapeutic vaccines. LIPO-5 is a therapeutic HIV vaccine made up of lipopeptides. Therapeutic vaccines are being investigated as an immunotherapeutic approach to correcting HIV-associated immune dysfunction, such as impaired dendritic cell (DC) responses to HIV and suboptimal adaptive immune responses (including HIV-specific T cell responses).4-7 A therapeutic vaccine may potentially increase the effectiveness of ART, simplify ART regimens, or allow for periodic structured treatment interruptions. A successful therapeutic vaccine would either completely eradicate the virus or improve an individual’s immune response to the point where it could suppress viral replication without ART. In either case, a therapeutic vaccine would help to circumvent a lifetime of ART.8

The LIPO-5 vaccine consists of the following five synthetic HIV-1 peptide fragments, which contain multiple CD8 and CD4 cell epitopes: Gag (amino acids 17 to 35), Gag (amino acids 253 to 284), Pol (amino acids 325 to 355), Nef (amino acids 66 to 97), and Nef (amino acids 116 to 145). The peptides are covalently attached to a palmitoyl-lysylamide moiety that facilitates entry into antigen-presenting DCs and enhances vaccine immunogenicity.2,9,10 LIPO-5 has been studied in early-phase HIV prevention trials. Its ability to elicit HIV-specific cell-mediated immune responses (when administered alone or in combination with other vaccines in a prime/boost strategy) has been studied in clinical trials involving healthy adults; results thus far appear to be mixed.1,2,9,11 As a therapeutic vaccine, LIPO-5 is being evaluated in a Phase II trial (NCT01492985) as a boost to a DNA vaccine (GTU-MultiHIV B) designed to generate HIV-specific immune responses that could control viral replication without the use of ART.12

The LIPO-5 vaccine antigens have also been developed into another vaccine product, known as LIPO-5-DC vaccine (BIIR/ANRS-HIVax-001). The LIPO-5-DC vaccine is made by ex vivo loading of an individual’s monocyte-derived DCs with the same mixture of antigenic lipopeptides contained in the LIPO-5 vaccine. The LIPO-5-DC vaccine has been studied in a Phase I therapeutic trial (NCT00796770).13,14


Select Clinical Trials


LIPO-5 therapeutic HIV vaccine
Study Identifiers: VRI02/ANRS 149 LIGHT; NCT01492985 
Sponsor: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Phase: II
Status: This study is ongoing, but not recruiting participants.
Study Purpose: The purpose of this proof-of-concept trial is to evaluate whether GTU-MultiHIV B (prime) combined with LIPO-5 (boost) can induce HIV-specific immune responses to control viral replication after treatment interruption.
Study Population

  • Participants are adults with chronic HIV infection who are asymptomatic and have been on ART for at least 18 months. 
  • Participants have had HIV RNA <50 copies/mL and CD4 cell counts ≥600 cells/mm3 for the previous 6 months and at the Week 3 screening visit. Participants have had nadir CD4 counts ≥300 cells/mm3 while on ART.12


Adverse Events


In the VRI02/ANRS 149 LIGHT study (NCT01492985), 103 participants enrolled to receive GTU-MultiHIV B and LIPO-5 vaccines or placebo vaccines. A preliminary safety analysis of 98 participants who had received at least one vaccine injection (93 of whom had received all injections) found that 94 participants experienced at least one adverse event (AE), most of which were mild. One participant experienced a serious adverse event (SAE) – arthritis – which was possibly related to vaccination (study vaccine or placebo). Among 90 participants who underwent a treatment interruption of ART, all had viral rebound. Twenty-three percent of participants had symptoms resembling acute HIV infection after treatment interruption of ART, although symptoms were mostly mild. One participant transmitted HIV infection during the period of treatment interruption.12,15


Drug Interactions


LIPO-5 drug interactions are currently unknown.


References


  1. ANRS HIV Vaccine Network. ANRS: HIV vaccine research programme. http://www.anrs.fr/content/download/1539/10054/file/hiv. Published December 2010. Accessed October 17, 2016.
  2. Salmon-Céron D, Durier C, Desaint C, et al. Immunogenicity and safety of an HIV-1 lipopeptide vaccine in healthy adults: a phase 2 placebo-controlled ANRS trial. AIDS. 2010;24(14):2211-2223.
  3. Treatment Action Group website. Research toward a cure trials. http://www.treatmentactiongroup.org/cure/trials. Accessed January 14, 2019.
  4. Lederman M, Rodriguez B, Sieg S. Immunopathogenesis of HIV Infection. In: Coffey S, Volberding P, eds. HIV InSite Knowledge Base. University of California San Francisco; 2004. http://hivinsite.ucsf.edu/InSite?page=kb-00&doc=kb-02-01-04. Accessed January 14, 2019.
  5. Miller E, Bhardwaj N. Advances in dendritic cell immunotherapies for HIV-1 infection. Expert Opin Biol Ther. 2014;14(11):1545-1549.
  6. Smith PL, Tanner H, Dalgleish A. Developments in HIV-1 immunotherapy and therapeutic vaccination. F1000Prime Rep. 2014;6(43). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047951/. Accessed January 14, 2019.
  7. Routy J-P, Boulassel M-R, Yassine-Diab B, et al. Immunologic activity and safety of autologous HIV RNA–electroporated dendritic cells in HIV-1 infected patients receiving antiretroviral therapy. Clin Immunol. 2010;134(2):140.
  8. Graziani GM, Angel JB. Evaluating the efficacy of therapeutic HIV vaccines through analytical treatment interruptions. J Int AIDS Soc. 2015;18(1):20497.
  9. Frey SE, Peiperl L, McElrath MJ, et al. Phase I/II randomized trial of safety and immunogenicity of LIPO-5 alone, ALVAC-HIV (vCP1452) alone, and ALVAC-HIV (vCP1452) prime/LIPO-5 boost in healthy, HIV-1-uninfected adult participants. Clin Vaccine Immunol. 2014;21(11):1589-1599.
  10. Castelli FA, Szely N, Olivain A, et al. Hierarchy of CD4 T cell epitopes of the ANRS Lipo5 synthetic vaccine relies on the frequencies of pre-existing peptide-specific T cells in healthy donors. J Immunol. 2013;190(11):5757-5763.
  11. Lelièvre J-D, Lacabaratz C, Wiedemann A, et al. Immunogenicity and safety of 4 prime-boost combinations of HIV vaccine candidates (MVA HIV-B; LIPO-5; GTU-MultiHIV B) in healthy volunteers - ANRS/INSERM VRI01 phase I/II randomized trial. Poster presented at: International AIDS Society (IAS) Conference on HIV Science; July 23-26, 2017; Paris, France. Poster WEPEC0971. http://programme.ias2017.org//PAGMaterial/eposters/3520.pdf. Accessed January 14, 2019.
  12. French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS). Evaluation of a therapeutic immunization strategy associating a DNA vaccine (GTU-MultiHIV B) followed by a lipopeptide vaccine (LIPO-5) in the control of viral replication following antiretroviral treatment interruption in HIV-1 infected patients with a CD4 cell count ≥ 600/mm3. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 24, 2011. NLM Identifier: NCT01492985. https://clinicaltrials.gov/ct2/show/NCT01492985. Accessed January 14, 2019.
  13. Baylor Research Institute. Vaccination of HIV-1 infected patients with ex-vivo generated interferon-α dendritic cells loaded with HIV-1 lipopeptides and activated with lipopolysaccharide in addition to antiretroviral treatment: exploratory Phase I study-(DALIA Trial). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 21, 2008. NLM Identifier: NCT00796770. https://clinicaltrials.gov/ct2/show/NCT00796770. Accessed January 14, 2019.
  14. Lévy Y, Thiébaut R, Montes M, et al. Dendritic cell-based therapeutic vaccine elicits polyfunctional HIV-specific T-cell immunity associated with control of viral load. Eur J Immunol. 2014;44(9):2802-2810.
  15. Levy et al. Preliminary safety results from VRI02 ANRS 149 Light (lipopeptide and DNA GTU HIV therapeutic trial). In: Chicago, IL; 2016. https://www.abstractstosubmit.com/hivr4p2016/eposter/main.php?do=YToyOntzOjU6Im1vZHVsIjtzOjY6ImRldGFpbCI7czo4OiJkb2N1bWVudCI7aTo3NTt9&. Accessed January 14, 2019.


Last Reviewed: January 14, 2019