Evaluating a parainfluenza virus 5-based vaccine in a host with pre-existing immunity against parainfluenza virus 5.

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.

Current status of vaccines for parainfluenza virus infections.

Parainfluenza viruses (PIV) have been generally disregarded as pathogens in spite of their importance in pediatric lower respiratory illness. Because PIVs account for 17% of hospitalized illness associated virus isolation, the development of PIV vaccine would be a major advance in preventing lower respiratory tract infection in infants and young children. We will review in detail several PIV vaccine candidates and recent newer approaches to PIV vaccine development. Intranasally administered bovine PIV3 (bPIV3) vaccine and cold-adapted PIV3 vaccine have been evaluated throughout the pediatric age spectrum. BPIV3 does not give a robust response to the heterotypic human strain although seroconversion rate to bPIV3 is 57-65%. However, bPIV3 vaccine is being used as an attenuated backbone for insertion of human PIV3 hemagglutinin-neuraminidase and fusion (F) proteins and a surface protein, F, of respiratory syncytial virus. The effectiveness of this vaccine against both PIV3 and RSV challenge has been demonstrated in African green monkeys. The cold-adapted PIV3 vaccine has been extensively evaluated and is safe and immunogenic in seronegative children with a seroconversion rate of 79%. These promising candidates deserve to enter into efficacy trials both for their ability to prevent PIV3 disease and as a model of protection against respiratory illness by mucosal vaccination.

Demonstration of 1-year duration of immunity for attenuated Bordetella bronchiseptica vaccines in dogs.

Three groups of healthy dogs with low antibody titers to Bordetella bronchiseptica (Bb), canine parainfluenza virus (CPI), and canine adenovirus type 2 (CAV-2) were used in this study. One group was vaccinated with a single dose of monovalent attenuated Bb vaccine and one group with a trivalent vaccine containing attenuated Bb, CPI, and CAV-2; dogs were vaccinated intranasally with a single dose of the respective vaccines. The third group served as unvaccinated controls. All vaccinated dogs subsequently developed serum antibody titers to Bb that persisted for at least 1 year. Following Bb challenge 1 year after vaccination, all vaccinated dogs, regardless of group, showed significantly fewer clinical signs and shed significantly fewer challenge organisms than unvaccinated controls. These results demonstrate that intranasal administration of a single dose of monovalent attenuated Bb vaccine or trivalent vaccine containing attenuated Bb, CPI, and CAV-2 provides 1 year of protection against Bb.

Investigation of several selected adjuvants regarding their efficacy and side effects for the production of a vaccine for parakeets to prevent a disease caused by a paramyxovirus type 3.

The infection with paramyxovirus type 3 (PMV-3) of parakeets can lead to severe illness in small psittacines (Neophema spp. and other parakeets) as well as in passerines (finches). The disease is characterized by acute or chronical pancreatitis and central nervous symptoms, such as torticollis as well as walking in circles and by high mortality rates in the affected flocks. As there is no licensed vaccine for psittacines available to prevent this disease. The aim of the following study was to find a suitable vaccine formulation for parakeets with inactivated PMV-3 and a well-tolerated and effective adjuvant. Seven adjuvants have been examined in ovo and in vivo regarding their efficacy and side effects. In these investigations, the classical Freund's complete Adjuvant (FCA) and Freund's incomplete Adjuvant (FICA) and Alhydrogel, but also the more recent developments TiterMax Gold, Specol, Gerbu Adjuvant 100, and Diluvac Forte have been used. Regarding its efficacy and side effects, the vaccine formulation "PMV-3/Specol" has been evaluated positively and can be recommended for the production of a PMV-3 vaccine for parakeets.

Newcastle disease and other avian paramyxoviruses.

Newcastle disease (ND), caused by avian paramyxovirus serotype 1 (APMV-1) viruses, is included in List A of the Office International des Epizooties. Historically, ND has been a devastating disease of poultry, and in many countries the disease remains one of the major problems affecting existing or developing poultry industries. Even in countries where ND may be considered to be controlled, an economic burden is still associated with vaccination and/or maintaining strict biosecurity measures. The variable nature of Newcastle disease virus strains in terms of virulence for poultry and the different susceptibilities of the different species of birds mean that for control and trade purposes, ND requires careful definition. Confirmatory diagnosis of ND requires the isolation and characterisation of the virus involved. Assessments of virulence conventionally require in vivo testing. However, in vitro genetic characterisation of viruses is being used increasingly now that the molecular basis of pathogenicity is more fully understood. Control of ND is by prevention of introduction and spread, good biosecurity practices and/or vaccination. Newcastle disease viruses may infect humans, usually causing transient conjunctivitis, but human-to-human spread has never been reported. Eight other serotypes of avian paramyxoviruses are recognised, namely: APMV-2 to APMV-9. Most of these serotypes appear to be present in natural reservoirs of specific feral avian species, although other host species are usually susceptible. Only APMV-2 and APMV-3 viruses have made a significant disease and economic impact on poultry production. Both types of viruses cause respiratory disease and egg production losses which may be severe when exacerbated by other infections or environmental stresses. No reports exist of natural infections of chickens with APMV-3 viruses.

Mixed paramyxovirus infection of wild and domestic birds in Israel.

Five cases of dual isolations of different serotypes of avian paramyxoviruses (APMV) from domestic and wild birds are described: one case of mixed infection by APMV-1 and APMV-4 and four cases of infection by APMV-1 and APMV-2 serotypes. The double infection was proven by consecutive isolations of two viruses from allantoic fluid samples derived from single swabs after their respective treatment by antisera against each suspected virus. The finding of double APMV infection in poultry farms appears to be important for epizootiology and pathogenesis of APMV-caused diseases.