We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Heroin-HIV-1 (H2) vaccine: induction of dual immunologic effects with a heroin hapten-conjugate and an HIV-1 envelope V2 peptide with liposomal lipid A as an adjuvant.
- Authors
Torres, Oscar B.; Matyas, Gary R.; Rao, Mangala; Peachman, Kristina K.; Jalah, Rashmi; Beck, Zoltan; Michael, Nelson L.; Rice, Kenner C.; Jacobson, Arthur E.; Alving, Carl R.
- Abstract
A synthetic heroin analog (MorHap) and a synthetic 42 amino acid V2 loop peptide from A/E strain of HIV-1 gp120 envelope protein that was previously used in a successful phase III vaccine trial were constructed as antigens together with liposomes containing monophosphoryl lipid A as an adjuvant, to explore the feasibility of producing a dual use vaccine both for treatment of heroin addiction and prevention of HIV-1 infection among injection drug users. The V2 peptide was tethered by a palmitoyl fatty acyl tail embedded in the liposomal lipid bilayer, and the heroin analog was conjugated to tetanus toxoid as a carrier protein that was mixed with the adjuvant. Upon comparison of a linear V2 peptide with a cyclic peptide, differences were found in the secondary configurations by circular dichroism, with the tethered cyclic peptide (palm-cyclic peptide) entirely in a random coil, and the tethered linear V2 peptide (palm-linear V2 peptide) entirely in a beta-sheet. Upon immunization of mice, palm-cyclic peptide induced anti-cyclic peptide endpoint titers >106 and was considered to be a better immunogen overall than palm-linear V2 peptide for inducing antibodies to gp120 and gp70-V1V2. The antibodies also inhibited the binding of V2 peptide to the HIV-1 α4β7 integrin receptor. Antibody titers to MorHap, even with the presence of injected cyclic peptide, were very high, and resulted in inhibition of the hyper-locomotion and antinociception effects of injected heroin. From these initial experiments, we conclude that with a potent adjuvant and mostly synthetic constituents, a vaccine directed to heroin and HIV-1 (H2 vaccine) could be a feasible objective. Drug addiction: Dual-use vaccine shows promise for heroin and HIV A vaccine designed to treat heroin addiction while at the same time preventing HIV infection elicited strong immune responses in mice. Scientists from the US government led by Carl Alving from the Walter Reed Army Institute of Research in Bethesda, Maryland, created a dual vaccine formulated with three main components: a segment of a protein expressed on the surface of HIV; synthetic molecules that resemble heroin and its degradation products; and a potent adjuvant to stimulate the immune system. Mice immunized with this vaccine had high antibody titers against the HIV surface protein as well as heroin and its derivatives. These mice also showed dulled responses to injected heroin. The findings suggest this vaccine strategy could help fight heroin abuse and the high risk of HIV infection among intravenous drug users.
- Subjects
HEROIN; HIV; AIDS vaccines; HAPTENS; IMMUNOLOGICAL adjuvants; HEROIN abuse
- Publication
NPJ Vaccines, 2017, Vol 2, Issue 1, pN.PAG
- ISSN
2059-0105
- Publication type
Article
- DOI
10.1038/s41541-017-0013-9