RETRACTED: Modified Newcastle disease virus vectors expressing the H5 hemagglutinin induce enhanced protection against highly pathogenic H5N1 avian influenza virus in chickens
Authors: Shin-Hee Kim
Peter L Collins
Anandan Paldurai
Sa Xiao
Siba K Samal
Journal: Vaccine (2014)
Discipline: IMMUNOLOGY
Keywords: H5N1 highly virulent avian influenza virus; Hemagglutinin; Newcastle disease virus; Vectored vaccine.
Affiliations: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, 8075 Greenmead Drive, College Park, MD, United States., Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United States., Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, 8075 Greenmead Drive, College Park, MD, United States. Electronic address: .

Abstract:  Naturally-occurring attenuated strains of Newcastle disease virus (NDV) are being developed as vaccine vectors for use in poultry and humans. However, some NDV strains, such as Beaudette C (BC), may retain too much virulence in poultry for safe use, and more highly attenuated strains may be suboptimally immunogenic. We therefore modified the BC strain by changing the multibasic cleavage site sequence of the F protein to the dibasic sequence of avirulent strain LaSota. Additionally, the BC, F, and HN proteins were modified in several ways to enhance virus replication. These modified BC-derived vectors and the LaSota strain were engineered to express the hemagglutin (HA) protein of H5N1 highly pathogenic influenza virus (HPAIV). In general, the modified BC-based vectors expressing HA replicated better than LaSota/HA, and expressed higher levels of HA protein. Pathogenicity tests indicated that all the modified viruses were highly attenuated in chickens. Based on in vitro characterization, two of the modified BC vectors were chosen for evaluation in chickens as vaccine vectors against H5N1 HPAIV A/Vietnam/1203/04. Immunization of chickens with rNDV vector vaccines followed by challenge with HPAIV demonstrated high levels of protection against clinical disease and mortality. However, only those chickens immunized with modified BC/HA in which residues 271-330 from the F protein had been replaced with the corresponding sequence from the NDV AKO strain conferred complete protection against challenge virus shedding. Our findings suggest that this modified rNDV can be used safely as a vaccine vector with enhanced replication, expression, and protective efficacy in avian species, and potentially in humans. 

Retracted: Yes

PubPeer comments:
  This article has been retracted at the request of the Editor-in-Chief as the Office of Research Integrity (ORI) notified the Publisher that a Federal Register notice, announcing U.S. Public Health Service findings and administrative actions, was issued in relation to this paper. The ORI findings were that the first author falsified and or fabricated Western blot images, specifically: - The blot which was used for Figure 3A, first blot of the second band, representing the negative expression of HA0 protein of the rLaSota virus in DF1 cells after 24 hour infection at Multiplicity of Infection (MOI) of 1, was fabricated by using the blank background from an uncorrelated original film. - The six (6) blots that were used for Figure 3A, bottom band, representing the expression of Newcastle disease virus (NDV) haemagglutinin-neuraminidase (HN) proteins in DF1 cells after 24 hour infection with six modified rNDV virus strains at MOI of 1, also were used in Figure 1B, bottom band, in J Gen Virol., 95 (2014) 331-336, https: doi.org 10.1099 vir.0.055285-0, to represent the expression of HN proteins of six different virus strains evaluated in infected DF1 cells at MOI of 0.1 in the presence of trypsin. ,