Induction of highly specific antibodies to a hapten but not to a carrier peptide by immunization
Inventors
Alving, Carl R. • Matyas, Gary R. • Jacobson, Arthur E. • Li, Fuying • Iyer, Malliga R. • Rice, Kenner C. • Cheng, Kejun • Mayorov, Alexander
Assignees
US Department of Health and Human Services • United States Department of the Army
Publication Number
US-9193739-B2
Publication Date
2015-11-24
Expiration Date
2033-02-08
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Abstract
In this application is described a composition and method for inducing in a subject anti-hapten antibodies without inducing antibodies to the carrier protein. Kits for designing and making compositions with desired haptens are also described.
Core Innovation
The invention provides a composition and method for inducing anti-hapten antibodies in a subject without inducing antibodies to the carrier protein. The composition comprises liposomes containing monophosphoryl lipid A (MPLA) and an immunoconjugate of a carrier peptide and a hapten. When a hapten is conjugated to a specific carrier peptide derived from the HIV-1 gp41 transmembrane protein (MPER) and presented on liposomes containing MPLA, antibodies to the hapten are induced without induction of antibodies to the carrier peptide.
The problem being addressed is immune interference during immunization with hapten-carrier conjugates. Typically, antibodies generated not only target the hapten but also the carrier, leading to dominant antibody specificity to the carrier, which interferes with subsequent induction of antibodies to the hapten. This interference limits the effectiveness of repeated immunization with the same carrier-hapten complex. Additionally, induction of antibodies to carrier peptides such as HIV-1 MPER could cause false positive diagnostic assays if the subject is not infected.
Claims Coverage
The patent claims encompass six main inventive features focused on novel haptens, specific immunoconjugates using carriers, compositions including these immunoconjugates, methods of inducing anti-heroin immune responses, and antibodies binding these immunoconjugates.
Chemical formulas of specific heroin-related haptens
The invention claims haptens with precise chemical formulas as defined in the claims, including six specific chemical formulas of heroin analog haptens capable of generating an immune response when conjugated.
Immunoconjugates linking haptens to carrier moieties
The invention covers immunoconjugates wherein the defined haptens are covalently linked to carrier moieties such as MPER peptide, tetanus toxin, keyhole limpet hemocyanin (KLH), or CRM to enhance immunogenicity.
Use of a 23 amino acid MPER peptide as carrier moiety
The invention specifies the use of MPER peptide with a particular 23 amino acid sequence (SEQ ID NO:1) as a carrier peptide in the immunoconjugates, sometimes incorporating a 15 amino acid universal T cell epitope spacer (SEQ ID NO:2 or SEQ ID NO:3) to facilitate effective conjugation.
Compositions comprising immunoconjugates with physiologically acceptable vehicles
The invention includes compositions that comprise an immunologically effective amount of the claimed immunoconjugates together with physiologically acceptable vehicles and optionally adjuvants, wherein the adjuvant is liposomes containing monophosphoryl lipid A (L(MPLA)), and the immunoconjugate can be embedded, associated, or attached to the L(MPLA).
Methods for inducing anti-heroin immune responses without inducing carrier antibody responses
Claimed methods involve immunizing a subject with the compositions containing the immunoconjugates to induce anti-heroin immune responses specifically without inducing immune responses to the carrier moieties such as MPER or tetanus toxin.
Antibodies and vaccine compositions targeting the immunoconjugates and heroin hapten
The invention claims antibodies that bind the immunoconjugates and specifically bind heroin, as well as vaccine compositions including the immunoconjugates and adjuvants for inducing protective or therapeutic immune responses.
The claims comprehensively cover the novel heroin-related haptens, their covalent conjugation to specified carrier moieties including MPER and tetanus toxin with optional spacers, formulations with liposomal MPLA adjuvant, methods of inducing targeted anti-heroin antibodies without carrier interference, and associated antibodies and vaccines designed from these compositions.
Stated Advantages
No immune interference due to antibodies to the peptide carrier, enabling effective induction of anti-hapten antibodies upon subsequent immunizations using the same carrier.
Avoidance of false positive diagnostic assays for HIV-1 due to lack of antibodies induced against the HIV-1 MPER peptide carrier.
Potent immune responses to heroin haptens are induced with liposomal MPLA as a safe and effective adjuvant system.
Flexibility in vaccine design allowing multiple haptens and carriers to be used together without immunological competition or interference.
Documented Applications
Vaccination against drug addiction caused by heroin and other drugs of abuse by inducing specific anti-hapten antibodies.
Immunogenic compositions for prophylactic or therapeutic treatment of subjects with specific drug addictions including heroin, morphine, methamphetamine, cocaine, and nicotine.
Production of antibodies for diagnostic assays detecting heroin or heroin analogs in samples.
Use of liposome-hapten-vaccine formulations to prevent intoxication, addiction, or severity of conditions related to drugs or infectious organisms.
Use in passive immunization protocols with antibodies derived from the immunoconjugates for treatment or drug cessation.
Provision of kits for designing and producing liposome-hapten compositions for treatment, vaccination, therapy, or diagnostics.
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