Relationship between the strength of antigen adsorption to an aluminum-containing adjuvant and the immune response

Hansen, Bethany; Sokolovska, Anna; HogenEsch, Harm; Hem, Stanley L.

doi:10.1016/j.vaccine.2007.06.049

Cited by 117 publications

(115 citation statements)

References 20 publications

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“…Indeed, several studies showed that a tight binding between antigens and aluminum salts would inhibit immunogenicity. Using -casein and dephosphorylated -casein as model antigens and non-treated/phosphatetreated aluminum hydroxide as adjuvants, it was shown that the geometric mean antibody titer in mice was inversely related to the adsorptive coefficient of antigens [58]. Similar results were obtained with HBsAg as a model antigen with aluminum hydroxide [53] or with aluminum hydroxyphosphate sulfate in mice [59].…”

Section: Degree and Strength Of Adsorption Vs Immunogenicitysupporting

confidence: 57%

Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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Section: Degree and Strength Of Adsorption Vs Immunogenicitysupporting

confidence: 57%

Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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“…19 Adsorption of antigen to the various aluminium compounds has long been accepted as important for their ability to induce good immune responses but this has recently been disputed. 44,45 Similarly, the significance of a depot of antigen at the injection site is still unclear; as is the effect on APCs. 21,22,24,25 In a recent study, aluminium, in the form of Imject Ò Alum, was shown to induce uric acid release at the injection site, leading to recruitment of inflammatory monocytes.…”

Section: Discussionmentioning

confidence: 99%

T‐helper 1 and T‐helper 2 adjuvants induce distinct differences in the magnitude, quality and kinetics of the early inflammatory response at the site of injection

et al. 2009

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T-helper 1 and T-helper 2 adjuvants induce distinct differences in the magnitude, quality and kinetics of the early inflammatory response at the site of injection Introduction With the vast amount of information on T-cell differentiation that has been obtained in recent years, and in particular that on the role of pathogen-associated molecular patterns (PAMPs) in the induction of immune responses, it should in theory be possible to tailor vaccines and adjuvants to selectively induce cell-mediated/humoral and T-helper 1/T-helper 2 (Th1/Th2) responses. This would obviously have tremendous impact on the ongoing

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“…Previously, others have reported an inverse correlation between the strength of the interaction of an antigen with an aluminum adjuvant and its ability to elicit an antibody response (15). PA has been determined to bind to an aluminum hydroxide adjuvant primarily through electrostatic interactions (28).…”

Section: Discussionmentioning

confidence: 99%

“…Deamidation of Asn occurs in vivo on a time scale ranging from a few seconds to centuries, depending on the local environment (10). In theory, deamidation might adversely affect the interaction of rPA with the aluminum adjuvant of the vaccine, might alter the epitope structure of the antigen, and/or might affect the ability of the protein to elicit T-cell help for antibody production which, in turn, might affect the vaccine immunogenicity (11)(12)(13)(14)(15).Earlier studies have demonstrated that certain Asn residues of rPA deamidate during the purification process and upon storage (8,16,17). Previously, we generated a mutant form of rPA in which the six Asn residues that are the most prone to deamidation were changed to Asp residues (six-Asp mutant rPA).…”

mentioning

confidence: 99%

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confidence: 99%

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Mechanistic Analysis of the Effect of Deamidation on the Immunogenicity of Anthrax Protective Antigen

Verma

Ngundi

Burns

2016

Clin Vaccine Immunol

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The spontaneous modification of proteins, such as deamidation of asparagine residues, can significantly affect the immunogenicity of protein-based vaccines. Using a "genetically deamidated" form of recombinant protective antigen (rPA), we have previously shown that deamidation can decrease the immunogenicity of rPA, the primary component of new-generation anthrax vaccines. In this study, we investigated the biochemical and immunological mechanisms by which deamidation of rPA might decrease the immunogenicity of the protein. We found that loss of the immunogenicity of rPA vaccine was independent of the presence of adjuvant. We assessed the effect of deamidation on the immunodominant neutralizing B-cell epitopes of rPA and found that these epitopes were not significantly affected by deamidation. In order to assess the effect of deamidation on T-cell help for antibody production elicited by rPA vaccine, we examined the ability of the wild-type and genetically deamidated forms of rPA to serve as hapten carriers. We found that when wild-type and genetically deamidated rPA were modified to similar extents with 2,4-dinitrophenyl hapten (DNP) and then used to immunize mice, higher levels of anti-DNP antibodies were elicited by wild-type DNP-rPA than those elicited by the genetically deamidated DNP-rPA, indicating that wild-type rPA elicits more T-cell help than the genetically deamidated form of the protein. These results suggest that a decrease in the ability of deamidated rPA to elicit T-cell help for antibody production is a possible contributor to its lower immunogenicity. Inhalation anthrax is a serious, often fatal, disease caused by Bacillus anthracis. Because of the fatal nature of the disease and the ease of dispersion of B. anthracis spores, B. anthracis is one of the most feared of all bioterror weapons. Due to the low incidence of natural anthrax disease in humans, anthrax vaccines are not given routinely. However, the potential for the use of B. anthracis as a bioterror agent has prompted stockpiling of anthrax vaccines by national governments. Long-term stability is a highly desired characteristic of a stockpiled vaccine since a long shelf life significantly decreases the cost of the stockpile.Many anthrax vaccines are based on protective antigen (PA), which is a nontoxic component of anthrax toxin. Anthrax toxin is a critical virulence factor of B. anthracis and is essential for disease symptomatology and progression (1, 2). The toxin is composed of PA, lethal factor (LF), and edema factor (EF). PA binds to cell receptors, heptamerizes, and then binds LF or EF to form lethal toxin (LT) and edema toxin (ET), respectively (3). Internalization of LT and ET leads to introduction of the enzymatically active effector proteins LF and EF into the cell cytosol where they exert their cytotoxicity (2). Vaccines based on PA or a recombinant form of PA (rPA) elicit antibodies, in particular functional toxinneutralizing antibodies (TNAs), that have been correlated with protection against the disease (4-6).Unfortunately...

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Relationship between the strength of antigen adsorption to an aluminum-containing adjuvant and the immune response

Cited by 117 publications

References 20 publications

Selection of Adjuvants for Enhanced Vaccine Potency

Selection of Adjuvants for Enhanced Vaccine Potency

T‐helper 1 and T‐helper 2 adjuvants induce distinct differences in the magnitude, quality and kinetics of the early inflammatory response at the site of injection

Mechanistic Analysis of the Effect of Deamidation on the Immunogenicity of Anthrax Protective Antigen

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