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Taming the Enemy
Published in Norman Begg, The Remarkable Story of Vaccines, 2023
The first adjuvants were aluminium salts. In the 1930s, they were used to improve the response to diphtheria and tetanus toxoids. Many vaccines in use today still contain aluminium hydroxide or aluminium phosphate – diphtheria, tetanus, whooping cough, hepatitis A and B to name a few. Some people have raised concerns about the safety of aluminium-containing vaccines. Aluminium is the most common metal in the earth’s crust, and we are exposed to it all the time. Most foods, drinking water and breast milk contain aluminium. The amount of aluminium in vaccines is considerably less than we consume on a daily basis.
Evaluation of Live Oral and Inactivated Intramuscular HRV Vaccines in Gn Pigs
Published in Lijuan Yuan, Vaccine Efficacy Evaluation, 2022
In this study, Gn pigs were inoculated IM three times on PID 0, 10, and 21 with 50 µg/dose purified CDC-9 TLP together with 600 µg/dose aluminum phosphate (Al[PO]4) adjuvant. Control pigs received the alum adjuvant only. On PID 28, all pigs were challenged orally with VirHRV Wa strain at the dose of 105FFU. Rectal swabs were collected from PCD 0–10 and virus shedding was measured by an antigen ELISA (Premium Rotaclone kit; Meridian Diagnostics, Cincinnati, OH). All five control pigs shed rotavirus antigen for three to five days; four of them had peak antigen titers of 8–32 on day four or five post-challenge. For six vaccinated animals, three shed no detectable antigen (50% protection rate) and the other three shed very low levels of antigen on day four only. Insignificant partial protection against diarrhea was found in this study and the data was not reported. Rotavirus-specific serum IgG and VN antibodies were induced by the vaccine and were further enhanced for an average of 57- and 11-fold post-challenge at PCD 15 compared to the titers at challenge (PID 28). This encouraging result from the Gn pig study provided supporting evidence for the filing of a US patent on the development of the CDC-9 inactivated vaccine in 2014 and the patent was granted in 2016 (Patent No. US 9,498,526 B2).
Immunization
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Michael F. Para, Susan L. Koletar, Carter L. Diggs
In addition to the antigenic components to be described below, vaccine preparations usually contain other constituents, some active and some inert. Among the most important are adjuvants, i.e., agents which increase immunogenicity. Adjuvants are proving to be especially important in recombinant subunit vaccines which as a group tend to be poorly immunogenic. It is now appreciated that bacterial whole cell vaccines may owe at least a portion of their immunogenicity to naturally occurring materials such as lipid A which act as natural adjuvants. Their particuiate nature may aiso be a contributing factor, since the immune system processes particulate and soluble antigens differently. Currently, the only adjuvant licensed in the United States is alum. Alum consists of either aluminum hydroxide or aluminum phosphate and is an insoluble substance with the property of adsorbing protein to its exposed surfaces. The efficacy of alum in promoting the immune response is poorly understood, but may be related to the concentration on the particles of alum of many molecules of antigen, thus presenting to the immune system particles covered with multiple epitopes. As occurs with cellular vaccines, so with alum-containing vaccines, the persistence of antigen at the injection site due to the decreased solubility of the complex may also play a role in increasing immunogenicity.
Beyond the amyloid hypothesis: how current research implicates autoimmunity in Alzheimer’s disease pathogenesis
Published in Critical Reviews in Clinical Laboratory Sciences, 2023
Miyo K. Chatanaka, Dorsa Sohaei, Eleftherios P. Diamandis, Ioannis Prassas
Aluminum was deemed another antigen that can trigger autoimmunity, due to its increased prevalence in water, processed foods, such as bread, ice cream, and chocolate, and various pharmacological products, such as antiperspirants and vaccines (diphtheria, tetanus, polio, etc.) [204,315]. Aluminum salts (aluminum phosphate, aluminum hydroxide) are used in vaccines to enhance the activation of immune responses, resulting in higher antibody production and T/B cell immunological memory [316]. Due to its high positive charge, it can bind to proteins, act as a cross-linker between proteins, induce protein oligomerization, and conformational changes that hinder degradation by proteases [204]. Specifically, in AD, aluminum has been linked to the oligomerization of Aβ [317,318]. Vodjani et al. examined the immune response to complexes that included aluminum hydroxide (AH-HSA), aluminum citrate (AC-HSA), and aluminum potassium sulfate bound to human serum albumin (HSA) (APS-HSA) in 94 HC, 47 AD, 47 Crohn’s disease, 47 celiac diseases and 47 mixed connective tissue disease (MCTD) patients using ELISA [204]. The results showed that the percentage of samples with elevated anti-AH-HSA, anti-AC-HSA, and anti-APS-HSA was higher in the non-control sera [204], including AD. The percentage of AD patients with increased anti-AH-HSA was 29%, for anti-AC-HSA 53%, and for anti-APS-HSA 63%, whereas for controls it was 10% [204]. This could indicate that aluminum binds to proteins that contain amino acids like histidine, tyrosine, and arginine in the brain, which form neoantigens that can then be targeted by the immune system [317–320].
Aluminum reproductive toxicity: a summary and interpretation of scientific reports
Published in Critical Reviews in Toxicology, 2020
The approximate systemic Al exposures after intramuscular (i.m.) injection of Al hydroxide (0.5%) and aluminum phosphate and amorphous aluminum hydrophosphate sulfate in Merck aluminum adjuvant (1.8%) are based on a study in rabbits (Flarend et al. 1997). The time course of Al absorption from the injection site appears to depend on its chemical species. In their, albeit limited, study addressing the rate and extent of Al absorption after injection, Flarend et al. (1997) gave i.m. injections of 26Al-labeled aluminum hydroxide and aluminum phosphate adjuvants to rabbits and determined the area under the curve (blood concentration x time) for 26Al compared to i.v. injection (which delivers 100% into the blood) of 26Al-labeled aluminum citrate. After i.m. 26Al-labeled aluminum hydroxide adjuvant injection, 17% appeared in the blood within 28 days. After the initial burst of blood 26Al at ∼10 h, blood 26Al was fairly constant for 28 days, suggesting a relatively stable absorption rate. This would equate to ∼0.5% of the dose per day. After i.m. 26Al-labeled aluminum phosphate adjuvant injection the amount in the blood was fairly constant for 28 days, representing a total of 51% of the injected 26Al, equating to 1.8% of the dose per day. The daily approximate systemic Al exposure after i.m. injection was assumed to be 0.5 or 1.8%, to a maximum of 100% if there was sufficient time.
Vaccines against anthrax based on recombinant protective antigen: problems and solutions
Published in Expert Review of Vaccines, 2019
Olga A. Kondakova, Nikolai A. Nikitin, Ekaterina A. Evtushenko, Ekaterina M. Ryabchevskaya, Joseph G. Atabekov, Olga V. Karpova
Over several decades, the aluminum compounds (aluminum hydroxide and aluminum phosphate) forming microparticles with the size of 1–20 μm in aqueous solutions have been used as adjuvants in licensed vaccines. Li et al. [157] have recently synthesized aluminum hydroxide particles of approximately 112 nm in size. The mice immunized with rPA adsorbed onto nanoparticles revealed significantly higher antibody levels than those immunized with rPA adsorbed on aluminum hydroxide microparticles [157]. The authors assume that strong adjuvant activity of aluminum hydroxide nanoparticles is connected with their ability to present antigens to APC, facilitating their processing with higher efficiency. In a number of studies, the nanoparticles of various nature were demonstrated to exhibit a stronger adjuvant activity than microparticles [158,159].