Mass vaccination with reassortment-impaired live H9N2 avian influenza vaccine

Avian influenza poses a severe threat to poultry production and global food security, prompting the development of vaccination programs in numerous countries. Modified live virus (MLV) vaccines, with their potential for mass application, offer a distinct advantage over existing options. However, con...

Full description

Saved in:
Bibliographic Details
Published in:npj vaccines 2024-08, Vol.9 (1), p.136-15, Article 136
Main Authors: Cargnin Faccin, Flavio, Cáceres, C. Joaquin, Gay, L. Claire, Seibert, Brittany, van Bentem, Nick, Rodriguez, Luis A., Soares Fraiha, Ana Luiza, Cardenas, Matias, Geiger, Ginger, Ortiz, Lucia, Carnaccini, Silvia, Kapczynski, Darrell R., Rajao, Daniela S., Perez, Daniel R.
Format: Article
Language:English
Subjects:
631/326/590/1867
631/326/596/1578
Biomedical and Life Sciences
Biomedicine
Chickens
Drinking water
Food security
Immunization
Infectious Diseases
Influenza
Medical Microbiology
Poultry
Poultry production
Public Health
Vaccine
Vaccines
Virology
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Avian influenza poses a severe threat to poultry production and global food security, prompting the development of vaccination programs in numerous countries. Modified live virus (MLV) vaccines, with their potential for mass application, offer a distinct advantage over existing options. However, concerns surrounding reversion, recombination, and unintended transmission have hindered the progress of MLV development for avian influenza in poultry. To address these concerns, we engineered reassortment-impaired, non-transmissible, safe, immunogenic, and protective MLVs through the rearrangement of internal gene segments and additional modifications to the surface gene segments HA and NA. The unique peptide marker aspartic acid-arginine-proline-alanine-valine-isoleucine-alanine-asparragine (DRPAVIAN) was incorporated into HA, while NA was modified to encode the chicken interleukin-18 (ckIL18) gene (MLV-H9N2-IL). In vitro, the MLV-H9N2 and MLV-H9N2-IL candidates demonstrated stability and virus titers comparable to the wild-type H9N2 strain. In chickens, the MLV-H9N2 and MLV-H9N2-IL candidates did not transmit via direct contact. Co-infection studies with wild-type virus confirmed that the altered HA and NA segments exhibited fitness disadvantages and did not reassort. Vaccinated chickens showed no clinical signs upon vaccination, all seroconverted, and the inclusion of ckIL18 in the MLV-H9N2-IL vaccine enhanced neutralizing antibody production. A significant decrease in viral loads post-challenge underscored the protective effect of the MLVs. The MLV-H9N2-IL vaccine, administered via drinking water, proved immunogenic in chickens in a dose-dependent manner, generating protective levels of neutralizing antibodies upon aggressive homologous virus challenge. In summary, this study lays the groundwork for safe MLVs against avian influenza suitable for mass vaccination efforts.
ISSN:2059-0105
2059-0105
DOI:10.1038/s41541-024-00923-y