Stabilization of tetanus toxoid formulation containing aluminium hydroxide adjuvant against freeze-thawing

Stabilization of a recombinant ricin toxin A subunit vaccine through lyophilization

“…For example, low-temperature excursions, which may cause accidental freezing, occur in 75-100% of liquid vaccine formulations during their distribution [9]. Freezing may result in loss of antigenicity [10]. …”

“…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].…”

Osmolytes in vaccine production, flocculation and storage: a critical review

“…62 This ultimately results in inducing aggregation of the protein antigens or agglomerization of vaccine particle, leading to low efficacy. 63 It has been reported previously that osmolytic agents for instance, trehalose 64 and glucose 65 were capable of protecting aluminium oxyhydroxide gel matrix against freezing-induced agitation. This is because the osmolytes are able to resist the alteration in the gel shape, crystallinity etc., thereby preventing the adjuvant particle from aggregation.…”

“…66 In another development osmolytes for instance, arginine, glucose, and sorbitol (but not trehalose), were shown to be capable of protecting the adjuvant matrix from aggregation or distortion, and helps to retain integrity of tetanus toxoid. 65 Trehalose was however, shown to prevent or minimize the aggregation of alhydroxy gel formulation. 65 The mechanism by which osmolytes protect the gel matrix is believed to be due to maintaining hydration layer formed across the adjuvant matrix, thereby helping to retain the surface layer, and crystallinity of the gel matrix.…”

“…65 Trehalose was however, shown to prevent or minimize the aggregation of alhydroxy gel formulation. 65 The mechanism by which osmolytes protect the gel matrix is believed to be due to maintaining hydration layer formed across the adjuvant matrix, thereby helping to retain the surface layer, and crystallinity of the gel matrix. 65,67 There is no unifying condition under which a particular osmolytes is protective in case of alum adjuvant.…”