Evaluating a Parainfluenza Virus 5-Based Vaccine in a Host with Pre-Existing Immunity against Parainfluenza Virus 5

Zhenhai Chen,Biao He,Zhen F Fu,Stephen B Harvey,Pei Xu,Gregory W Salyards,Balazs Rada,Moriya Tsuji

doi:10.1371/journal.pone.0050144

Zhenhai Chen, Biao He + Show 6 more

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https://doi.org/10.1371/journal.pone.0050144

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Abstract

Parainfluenza virus 5 (PIV5), formerly known as simian virus 5 (SV5), is a paramyxovirus often referred to as canine parainfluenza virus (CPI) in the veterinary field. PIV5 is thought to be a contributing factor to kennel cough. Kennel cough vaccines containing live PIV5 have been used in dogs for many decades. PIV5 is not known to cause any diseases in humans or other animals. PIV5 has been used as a vector for vaccine development for humans and animals. One critical question concerning the use of PIV5 as a vector is whether prior exposure to PIV5 would prevent the use of PIV5-based vaccines. In this work, we have examined immunogenicity of a recombinant PIV5 expressing hemagglutinin (HA) of influenza A virus subtype 3 (rPIV5-H3) in dogs that were immunized against PIV5. We found that vaccination of the dogs containing neutralizing antibodies against PIV5 with rPIV5-H3 generated immunity against influenza A virus, indicting that PIV5-based vaccine is immunogenic in dogs with prior exposure. Furthermore, we have examined exposure of PIV5 in human populations. We have detected neutralizing antibody (nAb) against PIV5 in 13 out of 45 human serum samples (about 29 percent). The nAb titers in humans were lower than that in vaccinated dogs, suggesting that nAb in humans is unlikely to prevent PIV5 from being an efficacious vector in humans.

Highlights

Parainfluenza Virus 5 (PIV5) is a non-segmented negative strand RNA virus (NNSV)
Infection of ‘‘naıve’’ Dogs with PIV5 and rPIV5-H3 While our prior studies indicate that rPIV5-H3 is effective in generating immunity in mice against influenza virus, it is not clear whether the same virus can be effective in generating immunity in dogs
One is based on the conditions used for virus isolation in the human studies, i.e. the labs used monkey cell lines which can be persistently infected with PIV5, and these cells often show no detectable cytopathic effects [6,7]

Summary

Introduction

Parainfluenza Virus 5 (PIV5) is a non-segmented negative strand RNA virus (NNSV). It is a member of the Rubulavirus genus of the family Paramyxoviridae, which includes mumps virus, human parainfluenza virus type 2 (HPIV2) and type 4 (HPIV4) [1]. The origin and natural host of PIV5 is not clear. PIV5 was first isolated from monkey cells as a contaminant in 1956, the original name SV5 [2]. Subsequent serological testing of wild monkeys indicated no exposure to this virus. All evidence to date indicates that PIV5 is not a simian virus. The virus was renamed parainfluenza virus 5 (PIV5) by International Committee on Taxonomy of Viruses in 2009

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