Relationship between tightness of binding and immunogenicity in an aluminum-containing adjuvant-adsorbed hepatitis B vaccine

Egan, Patricia M.; Belfast, Mary; Giménez, Juliana; Sitrin, Robert D.; Mancinelli, Ralph

doi:10.1016/j.vaccine.2009.03.054

Cited by 49 publications

(36 citation statements)

References 23 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: 59%

Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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Section: Degree and Strength Of Adsorption Vs Immunogenicitysupporting

confidence: 59%

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: 98%

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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“…Although the halflife of enterally absorbed Al elimination from the body is short (approximately 24 h), the same cannot be assumed for adjuvant-Al; because of ''depot effect'' a longer elimination is one of the very functions of adjuvants. Indeed a tightness of bonding between the aluminum adjuvant and the antigen is a desired feature that can be used to predict immunogenicity of vaccines (Egan et al, 2009). …”

Section: Discussionmentioning

confidence: 99%

Infants' exposure to aluminum from vaccines and breast milk during the first 6 months

Dórea

Marques

2009

J Expo Sci Environ Epidemiol

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The success of vaccination programs in reducing and eliminating infectious diseases has contributed to an ever-increasing number of vaccines given at earlier ages (newborns and infants). Exposure to low levels of environmental toxic substances (including metals) at an early age raises plausible concerns over increasingly lower neuro-cognitive rates. Current immunization schedules with vaccines containing aluminum (as adjuvant) are given to infants, but thimerosal (as preservative) is found mostly in vaccines used in non-industrialized countries. Exclusively, breastfed infants (in Brazil) receiving a full recommended schedule of immunizations showed an exceedingly high exposure of Al (225 to 1750 mg per dose) when compared with estimated levels absorbed from breast milk (2.0 mg). This study does not dispute the safety of vaccines but reinforces the need to study long-term effects of early exposure to neuro-toxic substances on the developing brain. Pragmatic vaccine safety needs to embrace conventional toxicology, addressing especial characteristics of unborn fetuses, neonates and infants exposed to low levels of aluminum, and ethylmercury traditionally considered innocuous to the central nervous system.

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Relationship between tightness of binding and immunogenicity in an aluminum-containing adjuvant-adsorbed hepatitis B vaccine

Cited by 49 publications

References 23 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

Infants' exposure to aluminum from vaccines and breast milk during the first 6 months

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