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The Inducible System: Antigens
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Adjuvants (from the Latin adjuvare, meaning to help) are substances added to antigen preparations to enhance their immunogenicity. This type of help is important if the antigen is not very immunogenic or in short supply. Adjuvants may or may not be immunogenic in themselves. They are frequently irritating and cause mild inflammation, thus activating cells of the immune system and attracting them to the site of antigen deposition. Some adjuvants bind the antigen tightly and release it slowly after injection, thus prolonging the antigenic stimulation. Most vaccines used in human and veterinary medicine contain adjuvants. Alum (aluminum potassium sulfate) is the most commonly used adjuvant in human medicine. In addition to delaying the release of the antigen, the high salt concentration precipitates the antigen, making it a larger target for phagocytosis by antigen presenting cells.
Byzantium
Published in Michael J. O’Dowd, The History of Medications for Women, 2020
During the Byzantine era Paul of Aegina advised powdered round alum wirh herbs as an application for hemorrhoids and described its use: as a vaginal contraceptive; for soothing genital lesions; for uterine hemorrhage; and for fissures or condylomata in the genital area (Adams, 1844 vol. 1, p. 603). Alum retained its popularity as a medication in obstetrics and gynecology through the centuries. James Wolveridge advised a tutia of burnt alum, red lead, pompholyx, and sugar candy for application to the breast to suppress milk formation and to prevent inflammation (1671 p. 139). In France, the most famous obstetrician of the seventeenth century, François Mauriceau, the Parisian accoucheur, wrote in 1683 of painful nipples during breastfeeding ‘to these sore nipples desiccative Medicines may be applied, as Allum ... but especially care must be taken, that nothing be applied to disgust the Childe, wherefore many content themselves to use only Honey of Roses’. Mauriceau prescribed alum for application to bleeding hemorrhoids in pregnancy, and also to the newborn’s cord.
Chimeric VLPs
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
Finally, the PP7 and MS2 VLPs displaying the L2 epitope 17–31, as presented in the vaccine Table 22.1, were subjected to thorough preclinical refinements (Tumban et al. 2015). As shown above, the immunization with the vaccine candidate VLPs carrying the L2 epitope of HPV16, or, in other words, 16L2 VLPs, elicited high titer and broadly cross-reactive and cross-neutralizing antibodies against diverse HPV types. The two refinements were introduced for the candidate vaccines, with an eye toward enhancing efficacy and clinical applicability in the developing world. First, the role of antigen dose and boosting on immunogenicity was addressed. The 16L2-MS2 VLPs at doses ranging from 2−25 μg with or without alum demonstrated high immunogenicity in mice at all doses. Alum appeared to have an adjuvant effect at the lowest dose. Although boosting enhanced antibody titers, even a single immunization could elicit strong and long-lasting antibody responses. Second, a method to enhance the vaccine stability was elaborated, generating dry powder vaccine formulations by a spray dry apparatus and protein stabilizers.
Preclinical developments in the delivery of protein antigens for vaccination
Published in Expert Opinion on Drug Delivery, 2023
Dylan A. Hendy, Alex Haven, Eric M. Bachelder, Kristy M. Ainslie
From simple beginnings of the administration of vaccinia to protect against cowpox, there has been an explosion in the development of new vaccine platforms. While attenuated and inactivated vaccines have shown clinical success, there is increasing public concern related to the safety of these types of vaccines. Due to this, the development of subunit vaccines is of great interest; however, subunit vaccines introduce many potential barriers to clinical translation. For example, subunit antigens are often not immunogenic enough on their own and require the delivery of immunopotentiating adjuvants. Currently, alum is a commonly used FDA-approved adjuvant that is found in many clinically available vaccines. However, alum falls short in that is does not promote a balanced Th1/Th2 response that is desired for increased efficacy. Due to this, there has been application of other adjuvants such as MPL, CpG, and QS-21 that produce a better Th1 response.
Cyclodextrin metal-organic framework as vaccine adjuvants enhances immune responses
Published in Drug Delivery, 2021
Congcong Li, Chaoxi Chen, Yucai Wei, Min Tan, Shuo Zhai, Juebo Zhao, Lu Wang, Tao Dai
Vaccination is effective and powerful in preventing and treating infections. Compared with the traditional inactivated and attenuated vaccines, protein antigen-based vaccines have better safety and lower cost, but protein antigens are easy to degrade, with poor immunogens when administered alone (Bobbala & Hook, 2016). Therefore, the application of antigen-based vaccines in biomedicine is limited. Thus, it is essential to use the delivery vehicle and adjuvant to improve immune response (Baldwin et al., 2008; Zhao et al., 2020). Freund’s complete adjuvant (FCA), the most common adjuvants, has been extensively used in animal vaccines because of its particular strong stimulant to both cellular and humoral immunities (Li et al., 2019). However, FCA can cause serious adverse reactions, including persistent pain, local tissue necrosis, and tumor-like hyperplasia at the injection site (Lukacs et al., 2015; Nakamura et al., 2020). Currently, alum with high safety is the only adjuvant approved by the Food and Drug Administration (FDA) for human vaccines. However, alum also has some disadvantages, such as anergy to cellular immunity and poor immunogenicity (Kool et al., 2012). Therefore, it is urgent to develop new vaccine adjuvants with great potency but much lower toxicity.
Cancer immunotherapy using a polysaccharide from Codium fragile in a murine model
Published in OncoImmunology, 2020
Hae-Bin Park, Seong-Min Lim, Juyoung Hwang, Wei Zhang, SangGuan You, Jun-O Jin
Induction of cancer Ag-specific immune activation is one of the immunotherapy strategies used to treat cancer.26,27,40 Although cancer cells over-express Ag candidate proteins, these proteins are not immunogenic as they are produced from the somatic cells without mutation. Therefore, immune stimulatory molecules or adjuvants are required to elicit cancer Ag-specific immune activation.41 Adjuvants activate APCs including DCs, macrophages, and B cells, which promote Ag-specific T-cell immunity.27,41 DCs are the most potent population involved in the induction of T-cell proliferation and activation.27 Therefore, many types of DC-targeting adjuvants have been developed and tested. Alum is one of the adjuvants approved by the US FDA that is known to enhance Ag-specific immune-response activation in humans.16 Many types of vaccines contain alum as an adjuvant.42 However, alum-induced immune activation is limited to Ab production or humoral immunity.16,42,43 In addition, monophosphoryl lipid A (MPLA), a toll-like receptor 4 (TLR4) ligand, is used as an adjuvant to enhance anti-cancer immunity, but MPLA is not water soluble and remains toxic to humans. The MPLA was modified for reducing toxicity from LPS.44 In this study, we found a novel adjuvant CFP which promotes immune activation including Th1 and CTL responses. CFP is a natural product and water soluble. As shown the conversion of LPS into less cytotoxic MPLA, the CFP will further study for modify to reduce cytotoxicity in the animal and human by composition analysis and development of derivatives.