Enabling Lyophilized Pneumococcal Conjugate Vaccines Through Formulation Design and Excipient Selection Suitable for A Multivalent Adjuvanted Vaccine

Abstract

Despite a consistent benefit of existing pneumococcal conjugate vaccine (PCV) on invasive pneumococcal disease and pneumonia across different epidemiological settings a tremendous gap exists towards global PCV coverage. Currently, no lyophilized dosage form exists in the PCV global vaccine marketplace and currently licensed vaccines target some, but not all relevant serotypes of Streptococcus pneumoniae. The development of lyophilized presentations of an adjuvanted multivalent vaccine formulation that aligns with the evolving epidemiological assessment of the pneumococcal disease offers broader coverage with distinct cold chain and thermostability advantages. To make progress towards this goal, we evaluated the feasibility of developing new formulation to enable a lyophilized adjuvanted PCV vaccine containing 15 different serotypes. Our findings successfully demonstrate a formulation design space that enables enhanced physical stability which controls vaccine agglomeration, preserves in-vitro vaccine potency, maintains PCV antigen adsorption, and yields elegant lyophilized cakes with acceptable clinically relevant reconstitution times. This research also demonstrates the benefit of utilizing specific vaccine formulation excipients and the effectiveness of excipient combinations that may be beneficial for other multivalent adjuvant containing vaccines to enable novel lyophilized formulations necessary for improved global vaccine access.

On the role of excipients and their future development

“…For enhanced drug stability [3], excipients can help stabilize drugs and prevent degradation, but it is important to understand their interaction with drug targets to ensure that they do not interfere with drug activity or cause toxicity. Identification of new drug targets [4]. Excipients may have their own biological activity and could potentially be used to modulate specific targets.…”

The Optimal Concentration of Nanoclay Hydrotalcite for Recovery of Reactive and Direct Textile Colorants

“…The next step was to filter the solution by gravity for 48 h through filter paper and measure with the spectrophotometer to calculate the concentration of dye that was not absorbed by the nanoclay [ 73 , 74 ]. The nanoclays with the dye were lyophilized [ 75 , 76 ] to completely extract the water.…”

Direct and Reactive Dyes Recovery in Textile Wastewater Using Calcinated Hydrotalcite

“…until the 24 h. The solution was filtered with clay for 48 h and was spectrophotometrically measured in a Zuzi spectrophotometer (model 4251/50) to calculate the dye concentration that had not been absorbed by clay [24,25]. The nanoclays with the absorbed dye were lyophilized [26,27] to completely extract water in order to be measured in a Jasco V-670 doublebeam spectrophotometer between 190 and 2700 nm. Differences in color and total solar reflectance (TSR) were calculated [28].…”