Effect of Various Silicone Oil And Tungsten Levels on the Stability of a Monoclonal Antibody in Nine Commercially Available Prefilled Syringes.

Prefilled syringes are widely used as a primary container for therapeutic proteins because they are more convenient than glass vials. The stability of biologic molecules can be affected by different syringe materials and techniques, such as silicone oil levels and coating method, amount of tungsten remaining in the glass barrel after using a tungsten pin to create the needle hole, and end of the syringe, which can be Luer locked or pre-staked with a needle. We investigated the impact of these parameters by using a monoclonal antibody to collect the antibody's stability profile and the prefilled syringes' functionality data. Silicone oil levels had no impact on aggregation levels, and particle counts were lowest for silicone oil-free syringes. Functionality performance was similar and did not change throughout all stability time points for all syringe configurations. The break-loose force for Ompi syringes was initially lower and increased over time to align with those of the other configurations, all of which remained well below 25 N. Tungsten contaminants and agitation stress from shipping studies did not impact quality attributes. This work can help guide the development of similar products in prefilled syringes to ensure selection of the primary container that provides adequate stability for the protein, as well as maintain the desired functionality features over the shelf life of the drug product.

Structure-Based Design of Nipah Virus Vaccines: A Generalizable Approach to Paramyxovirus Immunogen Development.

Licensed vaccines or therapeutics are rarely available for pathogens with epidemic or pandemic potential. Developing interventions for specific pathogens and defining generalizable approaches for related pathogens is a global priority and inherent to the UN Sustainable Development Goals. Nipah virus (NiV) poses a significant epidemic threat, and zoonotic transmission from bats-to-humans with high fatality rates occurs almost annually. Human-to-human transmission of NiV has been documented in recent outbreaks leading public health officials and government agencies to declare an urgent need for effective vaccines and therapeutics. Here, we evaluate NiV vaccine antigen design options including the fusion glycoprotein (F) and the major attachment glycoprotein (G). A stabilized prefusion F (pre-F), multimeric G constructs, and chimeric proteins containing both pre-F and G were developed as protein subunit candidate vaccines. The proteins were evaluated for antigenicity and structural integrity using kinetic binding assays, electron microscopy, and other biophysical properties. Immunogenicity of the vaccine antigens was evaluated in mice. The stabilized pre-F trimer and hexameric G immunogens both induced serum neutralizing activity in mice, while the post-F trimer immunogen did not elicit neutralizing activity. The pre-F trimer covalently linked to three G monomers (pre-F/G) induced potent neutralizing antibody activity, elicited responses to the greatest diversity of antigenic sites, and is the lead candidate for clinical development. The specific stabilizing mutations and immunogen designs utilized for NiV were successfully applied to other henipaviruses, supporting the concept of identifying generalizable solutions for prototype pathogens as an approach to pandemic preparedness.