RT Journal Article
SR Electronic
T1 Quantitative Analysis of Vaccine Antigen Adsorption to Aluminum Adjuvant Using an Automated High-Throughput Method
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP 149
OP 162
DO 10.5731/pdajpst.2017.008250
VO 72
IS 2
A1 Patrick L. Ahl
A1 Sheng-Ching Wang
A1 Ramesh Chintala
A1 Christopher Mensch
A1 William J. Smith
A1 Marc Wenger
A1 Jeffrey Blue
YR 2018
UL http://journal.pda.org/content/72/2/149.abstract
AB Aluminum-containing adjuvants have been widely used in vaccine formulations to safely and effectively potentiate the immune response. The examination of the extent of antigen adsorption to aluminum adjuvant is always evaluated during the development of aluminum adjuvant containing vaccines. A rapid, automated, high-throughput assay was developed to measure antigen adsorption in a 96-well plate format using a TECAN Freedom EVO® (TECAN). The antigen adsorption levels at a constant adjuvant concentration for each sample were accurately measured at 12 antigen/adjuvant (w/w) formulation ratios. These measurements were done at aluminum adjuvant concentrations similar to normal vaccine formulations, unlike previous non-automated and automated adjuvant adsorption studies. Two high-sensitivity analytical methods were used to detect the non-absorbed antigens. The antigen-to-adjuvant adsorption curves were fit to a simple Langmuir adsorption model for quantitatively analyzing the antigen to the adjuvant adsorption level and strength. The interaction of two model antigens, bovine serum albumin and lysozyme, with three types of aluminum adjuvant, were quantitatively analyzed in this report. Automated, high-throughput methodologies combined with sensitive analytical methods are useful for accelerating practical vaccine formulation development.LAY ABSTRACT: Vaccines are probably the most effective public health method to prevent epidemics of many infectious diseases. Many of the most effective vaccines contain aluminum adjuvant. This report describes novel technology that can be used to better optimize the efficacy and stability of aluminum adjuvant–containing vaccines.AAHSamorphous aluminum hydroxyphosphate sulfate adjuvantAlelemental aluminumAlOHaluminum hydroxide adjuvantAPaluminum phosphate adjuvantBPPBiologics Pilot PlantBSAbovine serum albuminBSA-Alexa488bovine serum albumin labeled with Alexa488 fluorophoreDtap-IVP/Hibdiphtheria, tetanus, cellular pertussis, inactivated polio virus, haemophilus influenza b vaccineCV%coefficient of variation %FDAFood and Drug AdministrationHep Ahepatitis A virusHep Bhepatitis B virusHPVhuman papilloma virusHThigh-throughputLINESTMicrosoft Excel® function that calculates the statistics of values fitting a line using the least squares methodLysolysozymeLyso-FITClysozyme labeled with FITC fluorophoreMMDMerck Manufacturing Division (West Point, PA)MWmolecular weightPelemental phosphorousPCV13pneumo conjugate vaccine 13 serotype antigenspIprotein isoelectric pointPZCpoint of zero chargeTECANTECAN Freedom EVO® laboratory automation instrumentVLPvirus-like particle