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

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.

A Novel Rabies Vaccine Based on a Recombinant Parainfluenza Virus 5 Expressing Rabies Virus Glycoprotein

“…The robust immune responses from the boost with live vaccine suggest that preexisting immunity to the viral vector did not affect the efficacy of the PIV5-based vaccine. Recently, we have found that dogs with neutralizing antibodies against PIV5 generated a protective immune response against influenza virus after immunization with PIV5 expressing HA of influenza A virus, demonstrating that a PIV5-based vaccine is effective in dogs with prior exposure (39). The use of rabies vaccines, especially live attenuated ones, in newborn dogs is limited due to maternal antirabies antibody, which can last as long as 6 months.…”

Single-Dose Vaccination of a Recombinant Parainfluenza Virus 5 Expressing NP from H5N1 Virus Provides Broad Immunity against Influenza A Viruses

“…Finally, a PIV5-based vaccine was shown to induce protective immunity in dogs that were exposed to PIV5. Levels of immunity were comparable in dogs with and those without prior PIV5 exposure, indicating that preexisting anti-PIV5 immunity does not negatively affect the immunogenicity of a PIV5-based vaccine (28).…”

“…Currently, kennel cough vaccines are mass produced by major veterinary vaccine companies. Fourth, a PIV5-vectored vaccine has been shown to be efficacious in animals (28)(29)(30)(31)(32). In our recent studies, we have found that a single-dose intranasal (i.n.)…”

Regulation of Viral RNA Synthesis by the V Protein of Parainfluenza Virus 5

“…PIV5 can infect humans and animals without causing any known symptoms or diseases (3,4). It has been used as a vector for vaccine development (5)(6)(7)(8)(9)(10)(11).…”