Aluminum Oxide Nanoparticles as Carriers and Adjuvants for Eliciting Antibodies from Non-immunogenic Haptens

Abstract

Functionalized nanomaterials have applications yet to be discovered, especially in the biological field and, in particular, the in vivo production of antibodies. In this paper, we show that aluminum oxide nanoparticles that are covalently coupled to haptens (small molecular mass compounds) activate the immune system, eliciting antibodies (polyclonal and monoclonal) specific for the herbicide atrazine, the antibiotic sulfasalazine, and the vitamin biotin in mice and rabbits. The particles play the role of carrier and adjuvant, with the immune response being dependent on size and crystallinity. The affinity constants of the antibodies are similar to those reached with traditional immunization strategies based on the use of carrier proteins. This approach has not been previously described, being of scientific and practical interest, as it can lead to immunogens safer than the conventional ones, potentially applicable to human vaccination. In addition, the useful advantages of this technique include the stability of the metallic particles, the synthesis of immunogens in organic media, the versatility of particle derivatization, the ease of purification, the full chemical characterization of immunogens, the lack of a requirement for an adjuvant, the reduction of the cross reactivity, and the low cost of materials. Also, the analytical performances of the immunoassays developed using these antibodies are comparable to those obtained by the standard protocols. Analytical applications of the developed ELISAs were fully demonstrated. Characterization (IgG nature, affinity constants, etc.) of the immunoreagents were also fully assessed.

Mechanistic understanding of nanoparticles’ interactions with extracellular matrix: the cell and immune system

“…On the other hand, NPs play the role of carrier and adjuvant, with the immune response being dependent on size and crystallinity [26]. Transport of the NPs through the ECM is more complicated due to its’ inherent mesh-like organization [27].…”

Novel approaches for the design, delivery and administration of vaccine technologies

“…Aluminium is a commonly used adjuvant in vaccines [88,[96][97][98]. This stimulated some studies into the conjugation of antigen to aluminium nanoparticles [97,98].…”

“…Aluminium is a commonly used adjuvant in vaccines [88,[96][97][98]. This stimulated some studies into the conjugation of antigen to aluminium nanoparticles [97,98]. These studies showed that the aluminium particles are able to play the role of both carrier and adjuvant to stimulate the immune system, although it has also been shown that aluminium particles are capable of adsorbing antigen so tightly that antigen structure is altered, which reduces vaccine efficacy [98,99].…”

Aluminum oxide nanowires as safe and effective adjuvants for next-generation vaccines

“…Aluminum (Al) salt-based adjuvants (most commonly in the form of aluminum oxyhydroxide (AlOOH), aluminum hydroxide (Al(OH) 3 ) are used in human vaccines since 1930s and are commonly referred to as "alum" [4][5][6]. The presence of oxygencontaining groups on their surface [7][8][9] provides fast antigen adsorption and yield a vigorous response from the immune system compared to alternatives [10]. While aluminum oxide (Al 2 O 3 ) is more robust, it is significantly less effective than other Al-based adjuvants and is commonly much less used.…”