Development of a New Lyophilized Live-Attenuated Measles-Rubella (MR) Vaccine Formulation Designed for Lower Cost Production in Africa (dataset)

This work describes a new, lyophilized, live-attenuated measles-rubella (MR) vaccine formulation designed for lower-cost production in Africa. The MR formulation consists of a newly developed stabilizer solution (containing only animal-free excipients) added to high-titer MR viral vaccine bulks (made in MRC-5 cells via a new production process) prior to lyophilization. Thus, this MR formulation contains relatively smaller proportional volumes of viral bulks and larger proportional volumes of viral bulks and stabilizers (5% and 95% (v/v), respectively). A lab-scale freeze-drying cycle and a qPCR-based viral infectivity assay were both implemented, followed by development of excipient screening conditions to identify stable MR formulations. First, we established that protein-based bulking agents (used in many commercial MR containing vaccines) could be avoided in lieu of sucrose/mannitol mixtures. Next, ~50 different excipients were screened, and two additional key stabilizing components were identified (both previously reported to stabilize MR viruses): sodium phosphate buffer and urea. A stability assessment of variations of a candidate lyophilized MR formulation was then performed using fixed levels of urea and sodium phosphate buffer, with varying amounts of sucrose and mannitol. Results revealed two key findings: (1) the inter-relationships between sucrose:mannitol ratios, physical cake integrity, and MR virus stability profiles, and (2) the optimized component concentrations in a top candidate formulation of 5% (w/v) mannitol, 5% (w/v) sucrose, 50 mM urea, 25 mM sodium phosphate buffer (pH 6.5), and 5% (v/v) viral bulks. This MR formulation was lyophilized at lab-scale in a single-dose format and displayed promising MR stability profiles during real-time and accelerated stability studies. Next, a 5-dose format was evaluated in a pilot-scale freeze-dryer (i.e., larger volumes of a 2X formulation filled into larger volume vials, lyophilized, and reconstituted to 1X concentration). Results demonstrated the feasibility of a new, lower-cost, lyophilized, multidose formulation for potential use with a live-attenuated MR vaccine candidate targeted for local production in Africa.