Nutrition and Immunity
R. J. Jarrett in Nutrition and Disease, 1979
There are major differences in the immune response when stimulated via the gut rather than systemically. The first experimental observation was that the oral administration of a hapten produces a state of specific systemic tolerance. A hapten is a small chemical radical with which an antibody can specifically react, but is too small in itself to directly induce an immune response. It has to combine with a protein before it becomes active, and if administered uncombined may link with the proteins of the recipient. If picryl chloride or 2-4 dinitro chloro-benzene are injected into the skin, a cell mediated and antibody response normally follows, causing an inflammatory lesion at the site. Prior ingestion of the hapten prevents this sensitisation from taking place. This is known, after its discoverers, as the Chase-Sulzberger phenomenon. Recent work has shown that partial tolerance to soluble protein antigens can be produced similarly.
The Immune System and its Function
Istvan Berczi in Pituitary Function and Immunity, 2019
All substances capable of eliciting an immune response are defined as antigens.59 The response induced may manifest as immunity (elicited by an immunogen) or tolerance (induced by a tolerogen). Depending on the conditions of antigen-lymphocyte interactions, the same compound may function as an immunogen, tolerogen, or both (e.g., by the induction of partial or split tolerance). Antibodies, or immune effector cells, generated during an immune response will have the potency of interacting specifically with the antigen, and also frequently with chemically related (cross-reactive) compounds. A memory exists for most antigens that were encountered by the immune system in the past, and a faster, more efficient immune response is induced upon secondary exposure (secondary or anamnestic reaction). The duration of this memory is variable. A great variety of small molecules that are not capable of inducing an immune response on their own are designated as haptens. Haptens may be rendered immunogenic, if covalently linked to an antigenic carrier molecule, or tolerogenic if coupled with a tolerogenic carrier.
Dictionary
Mario P. Iturralde in Dictionary and Handbook of Nuclear Medicine and Clinical Imaging, 1990
Carrier. A substance in ponderable amount which when associated with a trace of another substance will carry the trace with it through a chemical or physical process, especially a precipitation process. If the added substance is a different element from the trace, the carrier is called a nonisotopic carrier. A transmission signal upon which other signals can be piggybacked (modulated) for transmission. A carrier signal is a continuous signal transmitted over some medium at a particular frequency that is capable of being amplitude or frequency modulated to carry other signals containing data or information. An immunogenic substance that, when coupled to a hapten, renders the hapten immunogenic. An individual who harbors and sheds pathogens but who lacks overt symptoms of disease.
Vaccine development against methamphetamine drug addiction
Published in Expert Review of Vaccines, 2020
Md Kamal Hossain, Majid Hassanzadeganroudsari, Kulmira Nurgali, Vasso Apostolopoulos
The conjugate vaccines development strategies through hapten design have been studied most extensively for all the drugs of abuse including METH [8,9]. METH is a small molecule and the body’s immune system cannot recognize it. Therefore, METH or METH with a linker (hapten) needs to be tagged with a known immunogenic carrier to be recognized by the immune system and its effective processing (Figure 2) [8,29]. This strategy has been shown to be effective for both nicotine and cocaine vaccines and the strategy is viable for the application of developing a vaccine against METH [8]. In order to prevent METH from entering the central nervous system (CNS), a high concentration of anti-METH antibodies is required. The selectivity and affinity of the anti-METH antibody largely depend on an effective METH hapten molecule. This is a significant challenge as METH is a small molecule with limited chemical epitope [8,20]. Inclusion of a linker at the appropriate position of the ‘hapten’ (METH) is crucial for the generation of high antibody titers and antibody specificity [30]. Hence, the proper design of hapten is important for immune recognition due to its role in the presentation of target antigen to the antigen presenting cell. A series of METH haptens have been investigated (Table 1) by various research groups in the last few decades in regards to their efforts to develop a METH vaccine (hapten-carrier approach).
Is it possible to design a clinically viable heroin vaccine? The progress and pitfalls
Published in Expert Opinion on Drug Discovery, 2022
Therese J. Ziaks, Candy S. Hwang
The first proof-of-concept anti-heroin vaccine was developed in 1974 and produced a modest decrease in heroin self-administration in monkeys [10]. A heroin vaccine is comprised of three primary components: a hapten, an immunogenic carrier protein, and adjuvants. Haptens are structurally similar to heroin and are chemically linked to an immunogenic carrier protein to stimulate an immune response. This immunoconjugate is then paired with various adjuvants (i.e. additives that function as delivery vehicles or further stimulate the adaptive immune response) to enhance the vaccine profile [1]. During vaccination, the immune system generates polyclonal antibodies with specificity to heroin. If a subject uses heroin, these antibodies bind to the drug and form an antibody-drug complex which cannot pass through the blood-brain barrier (BBB), thus preventing a psychoactive high [11]. Given the vaccine’s inherent high-affinity and selectivity for heroin and the fact that antibodies do not directly interact with opioid receptors, a heroin vaccine could be administered with opioid medications.
Novel chimeric monoclonal antibodies that block fentanyl effects and alter fentanyl biodistribution in mice
Published in mAbs, 2021
Bhupal Ban, Rodell C. Barrientos, Therese Oertel, Essie Komla, Connor Whalen, Megan Sopko, Yingjian You, Partha Banerjee, Agnieszka Sulima, Arthur E. Jacobson, Kenner C. Rice, Gary R. Matyas, Vidadi Yusibov
Current research efforts are focused on developing alternatives or complementary modalities to the four approved products. An alternative approach to treat substance use disorders is use of vaccines or biologics that target specific drugs of abuse (DoA). Although the proof-of-concept for vaccines against DoA was demonstrated over 40 years ago,12,13 it has taken decades for the use of vaccines to treat SUDs to gain momentum. In the early 1970s, seminal efforts were devoted to hapten design that mimicked morphine, methamphetamine, and nicotine. These haptens, primarily, were used to generate antibodies for the detection of DoA. This area of research waned by the 1980s, but, over the past 15–20 years, interest in drug-specific antibodies resurfaced. As such, continued efforts to improve hapten design have led to vaccine candidates that can induce effective antibodies.14,15 When the DoA enters the bloodstream, these antibodies bind the drug and impede it from crossing the blood–brain barrier, thereby preventing it from interacting with its molecular target (e.g., the µ-opioid receptor) in the central nervous system (CNS).
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