A host-restricted viral vector for antigen-specific immunization against Lyme disease pathogen

Abstract

Newcastle disease virus (NDV) is an avian virus that is attenuated in primates and is a potential vaccine vector for human use. We evaluated NDV as a vector for expressing selected antigens of the Lyme disease pathogen Borrelia burgdorferi. A series of recombinant NDVs were generated that expressed intracellular or extracellular forms of two Borrelia burgdorferi antigens: namely, the basic membrane protein A (BmpA) and the outer surface protein C (OspC). Expression of the intracellular and extracellular forms of these antigens was confirmed in cultured chicken cells. C3H or Balb/C mice that were immunized intranasally with the NDV vectors mounted vigorous serum antibody responses against the NDV vector, but failed to mount a robust response against either the intracellular or extracellular forms of BmpA or OspC. In contrast, a single immunization of hamsters with the NDV vectors via the intranasal, intramuscular, or intraperitoneal route resulted in rapid and rigorous antibody responses against the intracellular or extracellular forms of BmpA and OspC. When groups of hamsters were separately inoculated with various NDV vectors and challenged with B. burgdorferi (108 cells/animal), immunization with vector expressing either intracellular or extracellular BmpA was associated with a significant reduction of the pathogen load in the joints. Taken together, our studies highlighted the importance of NDV as vaccine vector that can be used for simple yet effective immunization of hosts against bacterial infections including Lyme disease.

Generation by Reverse Genetics of an Effective, Stable, Live-Attenuated Newcastle Disease Virus Vaccine Based on a Currently Circulating, Highly Virulent Indonesian Strain

“…NDV titers in plaque forming units (PFU) were determined by plaque assay was performed in DF1 cells as previous described [17], [18]. Briefly, confluent DF1 cell monolayers were infected with 10-fold dilution of viruses.…”

Characterization and Genetic Analysis of Recent and Emergent Virulent Newcastle Disease Viruses in Egypt

“…The isolates Ck/ME3/Eg/16 and Ck/ME5/Eg/16 were further purified using plaque assay according to Xiao et al (2011) (Figure 2a,b), were detected by six out of seven built-in methods of the RDP4 software.…”

Avian Paramyxovirus Type-3 as a Vaccine Vector: Identification of a Genome Location for High Level Expression of a Foreign Gene

“…Lentogenic NDV strains have been widely used as live vaccines for the poultry. By taking advantage of the reverse-genetic technique, NDV-based recombinant vaccines have been generated and reported to be able to induce protective immune responses against avian and non-avian disease-causing viruses ( DiNapoli et al, 2009 , 2010 ; Khattar et al, 2010 , 2015 ; Kortekaas et al, 2010 ; Xiao et al, 2011 ; Kong et al, 2012 ; Kanabagatte Basavarajappa et al, 2014 ; Kim et al, 2014a , b ; Kim and Samal, 2016 ; Yu et al, 2016 ). However, commercial chickens often possess pre-existing antibodies including maternal antibodies against NDV due to routine vaccination programs ( Poissonnier and Teissier, 2013 ), resulting in a potential less-sensitivity to recombinant NDV vaccines expressing antigens of other avian pathogens.…”