A Single-Dose Recombinant Parainfluenza Virus 5-Vectored Vaccine Expressing Respiratory Syncytial Virus (RSV) F or G Protein Protected Cotton Rats and African Green Monkeys from RSV Challenge

Abstract

Human respiratory syncytial virus (RSV) is a common cause of severe respiratory disease among infants, immunocompromised individuals, and the elderly. No licensed vaccine is currently available. In this study, we evaluated two parainfluenza virus 5 (PIV5)-vectored vaccines expressing RSV F (PIV5/F) or G (PIV5/G) protein in the cotton rat and African green monkey models for their replication, immunogenicity, and efficacy of protection against RSV challenge. Following a single intranasal inoculation, both animal species shed the vaccine viruses for a limited time but without noticeable clinical symptoms. In cotton rats, the vaccines elicited RSV F- or G-specific serum antibodies and conferred complete lung protection against RSV challenge at doses as low as 10 PFU. Neither vaccine produced the enhanced lung pathology observed in animals immunized with formalin-inactivated RSV. In African green monkeys, vaccine-induced serum and mucosal antibody responses were readily detected, as well. PIV5/F provided nearly complete protection against RSV infection in the upper and lower respiratory tract at a dose of 10 PFU of vaccine. At the same dose levels, PIV5/G was less efficacious. Both PIV5/F and PIV5/G were also able to boost neutralization titers in RSV-preexposed African green monkeys. Overall, our data indicated that PIV5/F is a promising RSV vaccine candidate. A safe and efficacious respiratory syncytial virus (RSV) vaccine remains elusive. We tested the recombinant parainfluenza virus 5 (PIV5) vectors expressing RSV glycoproteins for their immunogenicity and protective efficacy in cotton rats and African green monkeys, which are among the best available animal models to study RSV infection. In both species, a single dose of intranasal immunization with PIV5-vectored vaccines was able to produce systemic and local immunity and to protect animals from RSV challenge. The vaccines could also boost RSV neutralization antibody titers in African green monkeys that had been infected previously. Our data suggest that PIV5-vectored vaccines could potentially protect both the pediatric and elderly populations and support continued development of the vector platform.

Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection

“…Perhaps virus transmission from camels to humans can be blocked, with concomitant immunization of high-risk human populations, as proposed by CEPI (The Coalition for Epidemic Preparedness Innovations) and WHO. As a vaccine vector, PIV5 has been effective in mice, cotton rats, hamsters, guinea pigs, ferrets, dogs, and nonhuman primates (25,(46)(47)(48)(49). It will be worthwhile to test PIV5-MERS-S in camels in the future.…”

Parainfluenza virus 5–vectored vaccines against human and animal infectious diseases

“…This work demonstrated that a single‐dose immunization with PIV5/F or PIV5/G elicited protective immunity against RSV challenge in mice. PIV5/F and PIV5/G were further evaluated as single‐dose inoculations in more relevant preclinical animal models . In cotton rats, both PIV5/F and PIV5/G elicited RSV‐specific serum antibodies and conferred complete protection in the lung against RSV challenge.…”

Respiratory Syncytial Virus Vaccine Approaches: a Current Overview

“…Parainfluenza virus (PIV) is the second most common cause of respiratory tract infection hospitalization in children. Two PIV5 chimeras expressing RSV F or RSV G protein were used to inoculate cotton rats and African green monkeys [23]. Although both chimeras fully protected naive animals from RSV infection, the RSV F protein chimera (PIV5/F) stimulated a higher antibody titer in African Green monkeys than RSV G protein (PIV5/G) [23].…”

“…Two PIV5 chimeras expressing RSV F or RSV G protein were used to inoculate cotton rats and African green monkeys [23]. Although both chimeras fully protected naive animals from RSV infection, the RSV F protein chimera (PIV5/F) stimulated a higher antibody titer in African Green monkeys than RSV G protein (PIV5/G) [23]. Also, they both boosted antibody levels in RSV pre-exposed African Green monkeys, suggesting that the PIV5/F vaccine could be helpful to naïve babies and pre-exposed elderly people [23].…”

“…Although both chimeras fully protected naive animals from RSV infection, the RSV F protein chimera (PIV5/F) stimulated a higher antibody titer in African Green monkeys than RSV G protein (PIV5/G) [23]. Also, they both boosted antibody levels in RSV pre-exposed African Green monkeys, suggesting that the PIV5/F vaccine could be helpful to naïve babies and pre-exposed elderly people [23]. Furthermore, genetic stability tests demonstrated that while random mutations were present in both in vivo (African green monkeys) and in vitro (Vero cells) passages, none of those mutations abolished antigen expression [24].…”