Development and Scalable Production of Newcastle Disease Virus-Vectored Vaccines for Human and Veterinary Use

Abstract

The COVID-19 pandemic has highlighted the need for efficient vaccine platforms that can rapidly be developed and manufactured on a large scale to immunize the population against emerging viruses. Viral-vectored vaccines are prominent vaccine platforms that have been approved for use against the Ebola virus and SARS-CoV-2. The Newcastle Disease Virus is a promising viral vector, as an avian paramyxovirus that infects poultry but is safe for use in humans and other animals. NDV has been extensively studied not only as an oncolytic virus but also a vector for human and veterinary vaccines, with currently ongoing clinical trials for use against SARS-CoV-2. However, there is a gap in NDV research when it comes to process development and scalable manufacturing, which are critical for future approved vaccines. In this review, we summarize the advantages of NDV as a viral vector, describe the steps and limitations to generating recombinant NDV constructs, review the advances in human and veterinary vaccine candidates in pre-clinical and clinical tests, and elaborate on production in embryonated chicken eggs and cell culture. Mainly, we discuss the existing data on NDV propagation from a process development perspective and provide prospects for the next steps necessary to potentially achieve large-scale NDV-vectored vaccine manufacturing.

Delivery of Fc-fusion Protein by a Recombinant Newcastle Disease Virus Vector

“…However, protein yield in eggs varied among different proteins and virus vectors. In particular, compared to other viruses used for protein expression, NDV is an effective vector for vaccine generation for mammals and humans [14,16] and has a good safety in these hosts, highlighting the advantages of this virus as promising vector for FCP delivery.…”

“…Newcastle disease virus (NDV), a member of paramyxovirus, is an important poultry virus, and is also an effective vector to express foreign proteins. The advantages of NDV as a vaccine vector for humans and animals have been extensively reviewed recently [14][15][16], suggesting that this virus may be also potentially used as a vector for in vivo expression and delivery of FCPs.…”

The production of Newcastle disease virus-like particles in Nicotiana benthamiana as potential vaccines

“…The production of these recombinant viral vector vaccines using the established low-cost egg-based production platform has been extensively investigated, although their production in cell culture systems is also possible, albeit at a higher production cost. For poultry vaccines, low manufacturing costs are imperative to ensure production margins are maintained ( Dimitrov et al., 2017 ; Fulber and Kamen, 2022 ; Nurzijah et al., 2022 ; World Organization for Animal Health (WOAH), 2022 ).…”

Purification of a recombinant oncolytic virus from clarified cell culture media by anion exchange monolith chromatography

“…A challenge for SGUC is its limited scalability which presents a bottleneck for large‐scale purification of NDV for clinical trials. More scalable purification steps such as membrane or column chromatography will be required to move NDV and other oncolytic viruses from clinic to market [17]. However, the size of many oncolytic viruses, including NDV, exceeds the pore diameter of most commercially available, bead‐based chromatography resins which, as a result, leads to reduced binding capacities and the requirement for large chromatography columns.…”