期刊
NPJ VACCINES
卷 2, 期 -, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41541-017-0013-9
关键词
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资金
- NIH Intramural Research Program of NIDA
- NIH Intramural Research Program of NIAAA
- Henry M. Jackson Foundation [W81XWH-07-2-067]
- U.S. Army Medical Research and Materiel Command
- NIDA (NIH) [1DP1DA034787-01]
- NATIONAL INSTITUTE ON DRUG ABUSE [DP1DA034787] Funding Source: NIH RePORTER
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 > 10(6) 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 alpha(4)beta(7) 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.
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