Effect of the strength of adsorption of hepatitis B surface antigen to aluminum hydroxide adjuvant on the immune response

Hansen, Bethany; Belfast, Mary; Soung, George; Song, Liping; Egan, Patricia M.; Capen, Robert; HogenEsch, Harm; Mancinelli, Ralph; Hem, Stanley L.

doi:10.1016/j.vaccine.2008.11.078

Cited by 88 publications

(63 citation statements)

References 17 publications

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“…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]. These results clearly suggest that the immune response could negatively correlate with the degree of adsorption of proteins on aluminum adjuvants [40].…”

Section: Degree and Strength Of Adsorption Vs Immunogenicitysupporting

confidence: 60%

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Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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Section: Degree and Strength Of Adsorption Vs Immunogenicitysupporting

confidence: 60%

“…It often correlates with the adsorption capacities [45,49] and can be significantly different depending on study conditions [53]. Generally, ligand exchange-based adsorption offers more binding strength than that from electrostatic attraction.…”

Section: Antigen Adsorption To Aluminum Saltsmentioning

confidence: 99%

Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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“…A default pathway for Th2 cell induction was recently reported when DCs were matured under suboptimal conditions (42). As the induction of Th1 or Th2 cells is directly influenced by the level of TCR-mediated signaling (43) Given the preserved Th2 responses, the lack of interference of free fluid Ag on B cell responses is readily explained: indeed, Ab responses increase when the tightness of Ag binding to aluminum salts is reduced (53,54). This lack of inhibition of Ab responses (55,56) may explain why this feature was not identified previously as a critical determinant of vaccine immunogenicity/ efficacy.…”

Section: Discussionmentioning

confidence: 97%

Synchronization of Dendritic Cell Activation and Antigen Exposure Is Required for the Induction of Th1/Th17 Responses

Kamath

Mastelic

Christensen

et al. 2012

The Journal of Immunology

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The dendritic cell (DC) targeting/activation patterns required to elicit Th1/Th17 responses remain undefined. One postulated requirement was that of a physical linkage between Ags and immunomodulators. Accordingly, the separate same-site administration of Ag85B–ESAT-6 (hybrid-1 protein; H1), a mycobacterial fusion Ag, and the CAF01 liposome-based adjuvant induced similar Ab and weak Th2 responses as those of coformulated H1/CAF01 but failed to elicit Th1/Th17 responses. Yet, this separate same-site injection generated the same type and number of activated Ag+/adjuvant+ DCs in the draining lymph nodes (LN) as that of protective H1/CAF01 immunization. Thus, targeting/activating the same DC population by Ag and adjuvant is not sufficient to elicit Th1/Th17 responses. To identify the determinants of Th1/Th17 adjuvanticity, in vivo tracking experiments using fluorescently labeled Ag and adjuvant identified that a separate same-site administration elicits an additional early Ag+/adjuvant− DC population with a nonactivated phenotype, resulting from the earlier targeting of LN DCs by H1 than by CAF01 molecules. This asynchronous targeting pattern was mimicked by the injection of free H1 prior to or with, but not after, H1/CAF01 or H1/CpG/ aluminum hydroxide immunization. The injection of soluble OVA similarly prevented the induction of Th1 responses by OVA/CAF01. Using adoptively transferred OT-2 cells, we show that the Ag targeting of LN DCs prior to their activation generates nonactivated Ag-pulsed DCs that recruit Ag-specific T cells, trigger their initial proliferation, but interfere with Th1 induction in a dose-dependent manner. Thus, the synchronization of DC targeting and activation is a critical determinant for Th1/Th17 adjuvanticity.

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“…However, enhanced immunogenicity was seen when a recombinant Candida antigen (rAls3p-N) was diluted with phosphate-buffered saline versus saline alone (44). Similarly, phosphate modulation of aluminum oxyhydroxide in both hepatitis B surface antigen and HIV-1 (SF162dV2gp140) subunit vaccines demonstrated enhancement of immunogenicity (8,9).…”

Section: Discussionmentioning

confidence: 99%

“…These effects include NLRP3 inflammasome activation, prostaglandin production, release of endogenous danger signals such as uric acid or DNA following cell death, binding to membrane lipids, and B cell priming (6,7). In a series of papers, Hansen and colleagues showed that the strength of antigen adsorption to an aluminum-containing adjuvant is inversely related to the immune response (8)(9)(10). They also showed that antigens do not need to be bound to the aluminum salt in order to benefit from the adjuvant effect (11) and that interstitial fluid can contribute to dissociation of the antigen-adjuvant complex in newly formulated vaccines but less so in older samples (12).…”

mentioning

confidence: 99%

Increasing the Potency of an Alhydrogel-Formulated Anthrax Vaccine by Minimizing Antigen-Adjuvant Interactions

Watkinson

Soliakov

Ganesan³

et al. 2013

Clin Vaccine Immunol

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f Aluminum salts are the most widely used vaccine adjuvants, and phosphate is known to modulate antigen-adjuvant interactions. Here we report an unexpected role for phosphate buffer in an anthrax vaccine (SparVax) containing recombinant protective antigen (rPA) and aluminum oxyhydroxide (AlOH) adjuvant (Alhydrogel). Phosphate ions bind to AlOH to produce an aluminum phosphate surface with a reduced rPA adsorption coefficient and binding capacity. However, these effects continued to increase as the free phosphate concentration increased, and the binding of rPA changed from endothermic to exothermic. Crucially, phosphate restored the thermostability of bound rPA so that it resembled the soluble form, even though it remained tightly bound to the surface. Batches of vaccine with either 0.25 mM (subsaturated) or 4 mM (saturated) phosphate were tested in a disease model at batch release, which showed that the latter was significantly more potent. Both formulations retained their potency for 3 years. The strongest aluminum adjuvant effects are thus likely to be via weakly attached or easily released native-state antigen proteins.

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Effect of the strength of adsorption of hepatitis B surface antigen to aluminum hydroxide adjuvant on the immune response

Cited by 88 publications

References 17 publications

Selection of Adjuvants for Enhanced Vaccine Potency

Selection of Adjuvants for Enhanced Vaccine Potency

Synchronization of Dendritic Cell Activation and Antigen Exposure Is Required for the Induction of Th1/Th17 Responses

Increasing the Potency of an Alhydrogel-Formulated Anthrax Vaccine by Minimizing Antigen-Adjuvant Interactions

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