Influence of Formulation pH and Suspension State on Freezing-Induced Agglomeration of Aluminum Adjuvants

Salnikova, Maya S.; Davis, Harrison; Mensch, Christopher; Celano, Lauren; Thiriot, David S.

doi:10.1002/jps.22815

Cited by 23 publications

(17 citation statements)

References 6 publications

(11 reference statements)

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“…Unfortunately, colloidal suspensions of aluminum adjuvant particles are unstable, and freezing-induced concentration of adjuvant suspensions causes aggregation during freeze-thawing [10,17,18,19,20]. Larger particles are less efficiently internalized by dendritic cells [21] and thus might be expected to produce a weaker immune response [22].…”

Section: Introductionmentioning

confidence: 99%

Stabilization of a recombinant ricin toxin A subunit vaccine through lyophilization

Hassett

Cousins

Rabia

et al. 2013

European Journal of Pharmaceutics and Biopharmaceutics

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Lyophilization was used to prepare dry, glassy solid vaccine formulations of recombinant ricin toxin A-chain containing suspensions of colloidal aluminum hydroxide adjuvant. Four lyophilized formulations were prepared by using combinations of rapid or slow cooling during lyophilization and one of two buffers, histidine or ammonium acetate. Trehalose was used as the stabilizing excipient. Aggregation of the colloidal aluminum hydroxide suspension was reduced in formulations processed with a rapid cooling rate. Aluminum hydroxide particle size distributions, glass transition temperatures, water contents, and immunogenicities of lyophilized vaccines were independent of incubation time at 40°C for up to 15 weeks. Mice immunized with reconstituted ricin toxin subunit A (RTA) vaccines produced RTA-specific antibodies and toxin-neutralizing antibodies (TNA) regardless of the length of high temperature vaccine storage or the degree of aluminum adjuvant aggregation that occurred during lyophilization. In murine studies, lyophilized formulations of vaccines conferred protection against exposure to lethal doses of ricin, even after the lyophilized formulations had been stored at 40°C for 4 weeks. A corresponding liquid formulation of vaccine stored at 40°C elicited RTA-specific antibody titers but failed to confer immunity during a ricin challenge.

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Section: Introductionmentioning

confidence: 99%

Stabilization of a recombinant ricin toxin A subunit vaccine through lyophilization

Hassett

Cousins

Rabia

et al. 2013

European Journal of Pharmaceutics and Biopharmaceutics

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“…Hence, viral diseases that usually require a Th1-mediated immunity and CTL activation for protection may not fully benefit from employing aluminum as an adjuvant. Importantly, aluminum salts render absorbed vaccines more susceptible to freeze and thaw stress resulting in vaccine structural damages and agglomeration [59,60]. In addition, alum absorption can induce destabilization of the conformational structure of the antigen or epitopes [61].…”

Section: Classes Of Adjuvants Tested For Vlp-based Vaccinesmentioning

confidence: 99%

Adjuvant formulations for virus-like particle (VLP) based vaccines

Cimica

Galarza

2017

Clinical Immunology

102

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The development of virus-like particle (VLP) technology has had an enormous impact on modern vaccinology. In order to optimize the efficacy and safety of VLP-based vaccines, adjuvants are included in most vaccine formulations. To date, most licensed VLP-based vaccines utilize the classic aluminum adjuvant compositions. Certain challenging pathogens and weak immune responder subjects may require further optimization of the adjuvant formulation to maximize the magnitude and duration of the protective immunity. Indeed, novel classes of adjuvants such as liposomes, agonists of pathogen recognition receptors, polymeric particles, emulsions, cytokines and bacterial toxins, can be used to optimize the immunostimulatory activity of a VLP-based vaccine. This review describes the current advances in adjuvant technology for VLP-based vaccines directed at viral diseases, and discusses the basic principles for designing adjuvant formulations for enhancing the vaccine immunogenicity.

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“…53 The extent of aluminum salt flocculation appears to depend on a number of factors, including charge on the particles at the formulation pH, excipients, ionic strength of formulation, and concentration of aluminum adjuvant. 54…”

Section: Physical Mechanisms Of Degradation Aggregationmentioning

confidence: 99%

Forced degradation studies: an essential tool for the formulation development of vaccines

Hasija¹,

Li²,

Rahman³

et al. 2013

VDT

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Forced degradation studies are typically conducted during the early development phase of vaccine candidates to obtain information on potential degradation pathways, support analytical methods development, and identify potential vaccine stabilizers and optimal conditions for long-term storage. The regulatory guidelines for forced degradation regarding biologics have few to no procedural instructions on how to approach forced degradation studies. In this review, we provide an overview of methods used to study forced degradation in vaccines, mechanisms of degradation, analytical methodology, forced degradation examples conducted for vaccine products, and a summary of stabilizers that are used to influence the results of new vaccine candidates.

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Influence of Formulation pH and Suspension State on Freezing-Induced Agglomeration of Aluminum Adjuvants

Cited by 23 publications

References 6 publications

Stabilization of a recombinant ricin toxin A subunit vaccine through lyophilization

Stabilization of a recombinant ricin toxin A subunit vaccine through lyophilization

Adjuvant formulations for virus-like particle (VLP) based vaccines

Forced degradation studies: an essential tool for the formulation development of vaccines

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