Modified Newcastle Disease virus as an improved vaccine vector against Simian Immunodeficiency virus

Abstract

SIV infection in macaques is a relevant animal model for HIV pathogenesis and vaccine study in humans. To design a safe and effective vaccine against HIV, we evaluated the suitability of naturally-occurring avirulent Newcastle disease virus (NDV) strains and several modified versions of NDV as vectors for the expression and immunogenicity of SIV envelope protein gp160. All the NDV vectors expressed gp160 protein in infected cells. The gp160 expressed by these vectors formed oligomers and was incorporated into the NDV envelope. All the NDV vectors expressing gp160 were attenuated in chickens. Intranasal immunization of guinea pigs with modified NDV vectors such as rNDV-APMV-2CS/gp160 and rNDV-APMV-8CS/gp160 (NDV strain LaSota containing the cleavage site sequences of F protein of avian paramyxovirus (APMV) serotype 2 and 8, respectively), and rNDV-BC-F-HN/gp160 (NDV strain BC containing LaSota F cleavage site and LaSota F and HN genes) elicited improved SIV-specific humoral and mucosal immune responses compared to other NDV vectors. These modified vectors were also efficient in inducing neutralizing antibody responses to tier 1 A SIVmac251.6 and tier 1B SIVmac251/M766 strains. This study suggests that our novel modified NDV vectors are safe and immunogenic and can be used as vaccine vector to control HIV.

The phosphatase and tensin homolog gene inserted between NP and P gene of recombinant Newcastle disease virus oncolytic effect test to glioblastoma cell and xenograft mouse model

“…In glioblastoma cells treated with rNDV-PTEN, antiapoptotic protein expression was strongly increased, suggesting that the apoptosis-resistance in glioblastoma had been decreased. NDV has been previously used for delivery of several genes [19,[48][49][50][51][52]. In addition, it has been confirmed that these rNDV-PTEN viruses have intact PTEN CDS even after 10 passages of subculture (Additional file 1: S3,S4).…”

Viruses as tools in gene therapy, vaccine development, and cancer treatment

“…An rNDV strain expressing the immunogenic gp160 envelope protein of simian immunodeficiency virus (SIV) induced specific humoral and mucosal responses to SIV when tested in a guinea pig model [ 90 ]. Another study demonstrated the stimulation of host immunity against poliomyelitis virus by injection with rNDV expressing the poliovirus precursor capsid protein and the associated protease [ 162 ].…”

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

“…This avoids the issue of pre-existing immunity in the population that can arise when using widely spread human viruses as viral vectors [ 12 ], such as highly seroprevalent adenoviruses [ 25 ]. In addition, NDV replicates efficiently in the respiratory tract, enabling it to be a vector for intranasal vaccines [ 20 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. This type of vaccine generates both mucosal and systemic immunity against the target disease, which is especially useful for vaccines against highly contagious respiratory diseases, including SARS-CoV-2 [ 2 , 33 ].…”

“…Another concern in poultry immunization is pre-existing immunity to NDV [ 64 ], which led to the development of chimeric NDV strains in which the native surface glycoproteins (F and HN) were substituted by the corresponding genes from another virus, namely APMV-8 [ 96 ] or APMV-2 [ 97 , 98 ]. Chimeric strains have also been developed to modulate virulence by substituting the F and HN proteins of the mesogenic BC strain (partly or completely) with the corresponding proteins from the lentogenic LaSota strain, or by modifying basic residues in the F protein cleavage site [ 32 , 99 ].…”