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

Vinoth K Manoharan,Celia C Labranche,Siba K Samal,David C Montefiori,Sunil K Khattar

doi:10.1038/s41598-018-27433-x

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.

Highlights

Human immunodeficiency virus-1 (HIV-1) infection can cause acquired immunodeficiency syndrome (AIDS) in humans[1]
Mesogenic Newcastle disease virus (NDV) strain Beaudette C (BC) has been tested as vector in rhesus macaques and it has been shown to replicate to a higher titer, did not cause any disease and induced superior antibody responses compared to the NDV strain LaSota[21]
The antibody titers in other groups were slightly higher than the rLaSota group. These results indicated that simian immunodeficiency virus (SIV) Env-specific IgG responses could be enhanced by using Modified-rNDV-avian paramyxovirus serotype-2 (APMV-2)-CS/160, Modified-rNDV-avian paramyxovirus serotype-8 (APMV-8)-CS/160 and Modified-rNDV-BC-F-HN/160 vectors

Summary

Introduction

Human immunodeficiency virus-1 (HIV-1) infection can cause acquired immunodeficiency syndrome (AIDS) in humans[1]. Several experimental HIV vaccines have been evaluated in macaques using SIV or simian-human immunodeficiency virus (SHIV) challenge models[3,4,5,6] These include recombinant proteins, peptides, inactivated viruses, DNA and live viral vectored vaccines either alone or in different prime-boost combinations. There have been six HIV vaccine efficacy trials in humans that have tested four different vaccine strategies but only RV144 trial showed a modest level of efficacy[7,8,9] The data from this trial or from a macaque challenge study[10] indicated the importance of HIV envelope (Env) protein expressed by recombinant viral vectors and further emphasized the role of antibodies in inducing protective immune responses against HIV. Our results identified several rNDV/SIV viruses that were highly immunogenic and elicited antibodies that neutralized the SIV mac251.6 strain in vitro

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