RESUMO
No licensed vaccines are available to protect against parainfluenza virus type 3 (PIV3), a significant health risk for infants. In search of a safe vaccine, we used an alphavirus-based chimeric vector, consisting of Sindbis virus (SIN) structural proteins and Venezuelan equine encephalitis virus (VEE) replicon RNA, expressing the PIV3 hemagglutinin-neuraminidase (HN) glycoprotein (VEE/SIN-HN). We compared different routes of intramuscular (i.m.), intranasal (i.n.), or combined i.n. and i.m. immunizations with VEE/SIN-HN in hamsters. Six months after the final immunization, all hamsters were protected against live PIV3 i.n. challenge in nasal turbinates and lungs. This protection appeared to correlate with antibodies in serum, nasal turbinates and lungs. This is the first report demonstrating mucosal protection against PIV3 for an extended time following immunizations with an RNA replicon delivery system.
Assuntos
Alphavirus/imunologia , Mucosa/imunologia , Vacinas contra Parainfluenza/imunologia , Vírus da Parainfluenza 3 Humana/imunologia , RNA Viral/imunologia , Replicon/imunologia , Administração Intranasal , Alphavirus/genética , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Cricetinae , Modelos Animais de Doenças , Vírus da Encefalite Equina Venezuelana/imunologia , Humanos , Imunização , Injeções Intramusculares , Vírus da Parainfluenza 3 Humana/crescimento & desenvolvimento , RNA Viral/genética , Replicon/genética , Sindbis virus/imunologia , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/uso terapêutico , Vacinas Sintéticas/imunologiaRESUMO
An infectious molecular clone was derived from the HIV-2UC2 isolate that previously was found to persistently infect and induce an AIDS-like disease syndrome in baboons. The molecularly cloned virus (HIV-2UC2mc) showed in vitro properties similar to those of the parental isolate with regard to T-cell tropism, cytopathicity, and the ability to infect primary baboon PBMC. Nevertheless, when inoculated into two baboons, the cloned virus showed a limited ability to replicate in these animals. DNA sequence analysis revealed a defective vpr gene in the UC2mc as well as in the pathogenic parental UC2 strain. Thus, the vpr gene is not required for the induction of disease in baboons. The attenuated infectious molecular clone of UC2 should be useful for future studies designed to map the genetic determinants of HIV-2 pathogenesis in the baboon model and to evaluate vaccine strategies.