Although mRNA still looms large in discussions about vaccines, the abatement of COVID-19 public-health emergencies has enabled biopharmaceutical companies to resume research and development (R&D) activities for multiple vaccine modalities. BPI’s January–February 2023 featured report takes stock of the growing number of options that are advancing through clinical development. Articles by contributors from ReiThera, the European Vaccine Initiative (EVI), and Nuvonis and Sartorius BIA Separations highlight the promise of several viral-vector systems for vaccine delivery, including human and simian adenoviruses (Ads), modified vaccinia Ankara (MVA), and Newcastle disease virus (NDV). Other articles in the report highlight concerns for vaccine manufacturing and distribution, with a writer from vaccine maker Syngene International laying out a case for expanding mRNA production capabilities around the globe and a contributor from the University of Maryland School of Pharmacy underscoring the industry’s need for simple analytical methods that can quickly identify vaccine products that have experienced adverse freezing events. Read the articles below to learn about obstacles that are hindering emerging vaccine approaches on their journeys to commercialization and distribution to global populations.
The Next Frontier for Viral-Vector Vaccines: Considerations for Manufacturing and Operations
by Brian Gazaille, with Stefano Colloca
Despite the excitement surrounding mRNA, some biopharmaceutical companies continue to develop capabilities for production of genetic vaccines based on simian adenovirus (Ad), adenoassociated virus (AAV), lentivirus (LV), modified vaccinia Ankara (MVA), and other viral vectors. Among those companies is Italian vaccine developer and manufacturer ReiThera, which in November 2022 received approval from regulatory authorities to begin operations at its new facility for large-scale production of viral vectors. Herein, BPI’s managing editor discusses facility requirements for products based on Ad and MVA, which receive less attention than other viral vectors but could play significant roles in mitigating the spread of common infectious diseases.
SARS-CoV-2 Variants: A Case for Expanding mRNA Vaccine Production Globally
by Mahesh Bhalgat
With new SARS-CoV-2 variants surfacing around the globe, mRNA-based vaccines will continue to play a significant role in abating the COVID-19 pandemic. But ensuring that such products are available worldwide is easier said than done. Bhalgat explores technical difficulties associated with manufacturing mRNA vaccines, then explains how such factors are magnified when products need to be produced for regions with limited economic means. Bhalgat argues for development of multiple regional centers for pandemic-vaccine production, highlighting India as a critical site.
Leishmaniasis — a Forgotten Epidemic
by Flavia D’Alessio, Sophie Houard, Stefan Jungbluth, Romina Di Marzo, Catarina Luís, and Ole Olesen
The World Health Organization (WHO) considers leishmaniasis to be one of the world’s most neglected tropical diseases (NTDs). Vaccines remain unavailable for human forms of the disease for several reasons, including the complexity of immune-system reactions to previous vaccine candidates and the need for cost-effective manufacturing processes that can be applied in endemic low- and middle-income countries. Herein, writers from the European Vaccine Initiative (EVI) explore difficulties associated with leishmaniasis-vaccine development and describe recent efforts to advance clinical candidates, including a promising product based on chimpanzee-derived adenoviral (ChAd) vectors.
Water-Proton Nuclear Magnetic Resonance Spectroscopy: Emerging Applications for Vaccine Quality Assessment
by Brian Gazaille, with Marc B. Taraban
Some vaccine drug products, especially those formulated with aluminum adjuvants, are “chill sensitive,” necessitating rigorous cold-chain management and careful examination of each vaccine lot for adverse freezing events. Currently, if a lot is suspected to have frozen during transport, a representative vial undergoes further testing. Available quantitative methods tend to destroy the representative drug product, and inconsistencies can arise with qualitative assessments. Herein, BPI’s managing editor speaks with Marc B. Taraban, an assistant research professor from the University of Maryland School of Pharmacy, about potential advantages from using water-proton nuclear magnetic resonance spectroscopy (wNMR) for nondestructive assessment of drug-product freezing events. The discussion reveals a breadth of possible applications for quality control testing of biopharmaceutical drug products, including vaccines, monoclonal antibodies (MAbs), and even gene therapies.
Production and Purification of Newcastle Disease Virus: A High-Yield Platform Process Based on a Novel Avian Cell Line and Monolith Chromatography
by Hana Jug, Natalija Hosta, Mojca Tajnik Sbaizero, Aleš Štrancar, Daniela Brodesser, Bianca Tisch, Theresa Heger, Markus Wolschek, Joachim Seipelt, and Manfred Reiter
(a sponsored contribution)
Historically, attenuated Newcastle disease virus (NDV) has been produced in embryonated chicken eggs or primary chicken embryo fibroblasts for application in veterinary vaccines. Recently, however, NDV has been evaluated as a vector for human vaccines against SARS-CoV-2, Ebola, H5N1 influenza, West Nile, and simian immunodeficiency viruses. Oncolytic NDV vectors also hold much promise as immunotherapies against various cancers. Regardless of application, NDV particles must meet certain criteria for yield, purity, and concentration. Herein, scientists from Nuvonis and Sartorius BIA Separations describe their optimization of a platform approach to NDV production and purification. Upstream steps leverage a novel quail-derived cell line that eliminates several immunogenic and allergenic properties of egg-based production systems. Downstream purification involves chromatographic separation based on sulfonate monolith columns. Together, the optimized processes result in NDV drug substances of high yield and purity.
