Establishing a Robust Manufacturing Platform for Recombinant Veterinary Vaccines: An Adenovirus-Vector Vaccine to Control Newcastle Disease Virus Infections of Poultry in Sub-Saharan Africa.

Omar Farnós,Héla Kallel,Alice Bernier,Khaled Trabelsi,Martha Yami,Amine A. Kamen,Esayas Gelaye,Kumar Subramani

doi:10.3390/vaccines8020338

Omar Farnós, Héla Kallel + Show 6 more

Open Access

https://doi.org/10.3390/vaccines8020338

Copy DOI

Abstract

Developing vaccine technology platforms to respond to pandemic threats or zoonotic diseases is a worldwide high priority. The risk of infectious diseases transmitted from wildlife and domestic animals to humans makes veterinary vaccination and animal health monitoring highly relevant for the deployment of public health global policies in the context of “one world, one health” principles. Sub-Saharan Africa is frequently impacted by outbreaks of poultry diseases such as avian influenza and Newcastle Disease (ND). Here, an adenovirus-vectored vaccine technology platform is proposed for rapid adaptation to ND or other avian viral threats in the region. Ethiopian isolates of the Newcastle Disease virus (NDV) were subjected to sequence and phylogenetic analyses, enabling the construction of antigenically matched vaccine candidates expressing the fusion (F) and hemagglutinin-neuraminidase (HN) proteins. A cost-effective vaccine production process was developed using HEK293 cells in suspension and serum-free medium. Productive infection in bioreactors (1–3 L) at 2 × 106 cells/mL resulted in consistent infectious adenoviral vector titers of approximately 5–6 × 108 TCID50/mL (approximately 1011VP/mL) in the harvest lysates. Groups of chickens were twice immunized with 1 × 1010 TCID50 of the vectors, and full protection against a lethal NDV challenge was provided by the vector expressing the F antigen. These results consolidate the basis for a streamlined and scalable-vectored vaccine manufacturing process for deployment in low- and medium-income countries.

Highlights

Newcastle Disease (ND) is considered one of the most critical diseases affecting poultry in sub-Saharan Africa
We present the design, development, and production in bioreactors of genotype-matched adenoviral vectored variants of Newcastle Disease virus (NDV) vaccine candidates expressing the F and HN
Four Newcastle disease virus field isolates collected during outbreaks which occurred between the years 2013 and 2018 in different regions of Ethiopia were subjected to sequence analysis

Summary

Introduction

Newcastle Disease (ND) is considered one of the most critical diseases affecting poultry in sub-Saharan Africa. Vaccines 2020, 8, 338 disadvantages such as the production of vaccines using specific pathogen-free embryonated eggs and the possibility of virus shedding leading to disease in non-vaccinated animals [4,5]. In the sub-Saharan African region, millions of chickens are farmed, with the majority being kept in villages and rural settings in scavenging production systems, with constrains of feed, management, and disease issues [8,9]. In these scenarios, ND has devastating effects on both the commercial farms and the village chickens [10]

Methods

Results

Conclusion