Evaluation of the Replication, Pathogenicity, and Immunogenicity of Avian Paramyxovirus (APMV) Serotypes 2, 3, 4, 5, 7, and 9 in Rhesus Macaques

Abstract

Avian paramyxoviruses (APMV) serotypes 1–9 are frequently isolated from domestic and wild birds worldwide. APMV-1 (also called Newcastle disease virus, NDV) is attenuated in non-human primates and is being developed as a candidate human vaccine vector. The vector potential of the other serotypes was unknown. In the present study, we evaluated nine different biologically- or recombinantly-derived APMV strains for the ability to replicate and cause disease in rhesus macaque model. Five of the viruses were: biologically-derived wild type (wt) APMV-2, -3, -5, -7 and -9. Another virus was a recombinant (r) version of wt APMV-4. The remaining three viruses were versions of wt rAPMV-2, -4 and -7 in which the F cleavage site had been modified to be multi-basic. Rhesus macaques were inoculated intranasally and intratracheally and monitored for clinical disease, virus shedding from the upper and lower respiratory tract, and seroconversion. Virus shedding was not detected for wt APMV-5. Very limited shedding was detected for wt rAPMV-4 and modified rAPMV-4, and only in a subset of animals. Shedding by the other viruses was detected in every infected animal, and usually from both the upper and lower respiratory tract. In particular, shedding over a number of days in every animal was observed for modified rAPMV-2, wt APMV-7, and modified rAPMV-7. Modification of the F protein cleavage site appeared to increase shedding by wt rAPMV-2 and marginally by wt rAPMV-4. All APMVs except wt APMV-5 induced a virus-specific serum antibody response in all infected animals. None of the animals exhibited any clinical disease signs. These results indicate that APMVs 2, 3, 4, 7, and 9 are competent to infect non-human primates, but are moderately-to-highly restricted, depending on the serotype. This suggests that they are not likely to significantly infect primates in nature, and represent promising attenuated candidates for vector development.

Newcastle Disease Virus as a Vaccine Vector for SARS-CoV-2

“…It is highly attenuated in all non-avian species, including humans, due to natural host-range restriction. The safety and immunogenicity of NDV-vectored vaccines have been extensively studied in monkeys, a non-human primate model that is closely related phylogenetically and anatomically to humans, and which is a good model for pre-clinical studies of human vaccines [ 8 , 21 , 22 , 23 , 24 , 25 ]. In one study, intranasal and intratracheal inoculation of African green and rhesus monkeys with 1 × 10 6.5 plaque forming units (PFU) per site with either a lentogenic strain (LaSota) or a mesogenic strain (Beaudette C) of NDV did not cause any clinical disease signs, and there was little or no virus shedding in throat swabs or tracheal lavage.…”

Avian Paramyxovirus: A Brief Review

“…Interestingly, chickens immunized by APMV‐8 showed reduced virus shedding upon virulent NDV challenge (Nayak et al., ). APMV‐8 also shows replication in a non‐avian host such as rhesus macaques, mice and hamsters but fail to cause any infection (Khattar et al., , ; Samuel et al., ).…”

“…Although APMV‐9 showed replication in chickens, but failed to produce visible signs of its infection (Kim et al., ). Avian Paramyxovirus Serotype‐9 replicates and causes mild disease in non‐avian hosts such as mice, hamster and rhesus macaques (Khattar et al., , ; Samuel et al., ).…”

“…The potential use of APMVs as a vaccine vector for human infectious diseases gained more momentum when it was shown that APMV‐1 to APMV‐9 can replicate in rhesus macaques. Moreover, it was also shown that APMV‐2, APMV‐3, APMV‐4, APMV‐7 and APMV‐9 can be served as a promising candidates for attenuated viral vector development (Khattar et al., ). The recombinant APMVs are also explored as live vaccines and vaccine vectors for animal uses in disease such as Newcastle disease (Kumar et al., ).…”

Proinflammatory response induced by Newcastle disease virus in tumor and normal cells

“…This virus has been reported to be an effective oncolytic agent in vitro and in vivo against many types of solid tumors such as hepatocellular carcinoma, pancreatic adenocarcinoma, melanoma, pleural mesothelioma, colorectal carcinoma, renal carcinoma, glioblastoma and many others,5,7–13 as well as in clinical studies in patients with glioblastoma multiforme, colorectal carcinoma, non-small cell lung carcinoma, renal carcinoma, breast adenocarcinoma, mesothelioma and pancreatic adenocarcinoma 14–18. NDV causes a disease that predominantly affects poultry, although infection in humans has been reported to cause conjunctivitis19,20 and/or mild flu-like symptoms 13–17,21. Based on their virulence on birds, NDV strains can be divided into three groups: lentogenic (low virulence), mesogenic (medium virulence) and velogenic (high virulence).…”