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Primary replication of a recombinant Sendai virus vector in macaques
Munehide Kano1, Tetsuro Matano2,1, Atsushi Kato1
1AIDS Research Centre1, Department of Viral Diseases and Vaccine Control2 and Division of Experimental Animal Research3, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-murayama, Tokyo 208-0011, Japan.
Abstract:
An efficient antigen expression system using a recombinant Sendai virus (SeV) has been established recently and its potential to induce resistance against immunodeficiency virus infections in macaques has been shown. SeV replication has been well characterized in mice, the natural host, but not in primates, including humans. Here, primary SeV replication was investigated in macaques. After intranasal immunization with a recombinant SeV expressing simian immunodeficiency virus Gag protein, SeV-Gag, robust gag expression was observed in the nasal mucosa and much lower but significant levels of gag expression were observed in the local retropharyngeal and submandibular lymph nodes (LN). Expression peaked within a week and lasted at least up to 13 days after immunization. SeV-Gag was isolated from nasal swabs consistently at day 4 but not at all at day 13. Gag expression was undetectable in the lung as well as in remote lymphoid tissues, such as the thymus, spleen and inguinal LN, indicating that the spread of the virus was more restricted in macaques than in mice. SeV-specific T cells were detectable in SeV-immunized macaques at day 7. Finally, no naive macaques showed significant levels of anti-SeV antibodies in the plasma, even after living in a cage together with an acutely SeV-infected macaque for 5 weeks, indicating that SeV transmission from SeV-infected macaques to naive ones was inefficient. None of the SeV-immunized macaques displayed appreciable clinical manifestations. These results support the idea that this system may be used safely in primates, including humans.
Insights
This study shows that a recombinant Sendai virus (SeV) expressing simian immunodeficiency virus Gag protein is safe and effective in macaques. The SeV-Gag system demonstrated robust gag expression and induced T cell responses with limited viral spread and inefficient transmission.
Area of Science:
- Virology
- Immunology
- Primate Research
Background:
- Recombinant Sendai virus (SeV) systems offer efficient antigen expression for vaccine development.
- SeV replication is well-understood in mice but less so in primates.
- Previous studies suggested SeV's potential against immunodeficiency virus infections in macaques.
Purpose of the Study:
- To investigate primary SeV replication and Gag expression in macaques after intranasal immunization with SeV-Gag.
- To assess the safety and immune response elicited by the SeV-Gag system in a primate model.
- To evaluate the potential for SeV transmission and clinical manifestations in immunized macaques.
Main Methods:
- Intranasal immunization of macaques with recombinant SeV expressing simian immunodeficiency virus Gag protein (SeV-Gag).
- Monitoring of Gag expression in various tissues and detection of SeV in nasal swabs.
- Assessment of SeV-specific T cell responses and anti-SeV antibody levels.
- Evaluation of viral spread, transmission efficiency, and clinical signs.
Main Results:
- Robust Gag expression was observed in the nasal mucosa and local lymph nodes, peaking within a week and lasting at least 13 days.
- SeV-Gag was isolated from nasal swabs up to day 4 but not day 13, with restricted viral spread to remote tissues.
- SeV-specific T cells were detected by day 7, and viral transmission between macaques was inefficient.
- No significant clinical manifestations were observed in SeV-immunized macaques.
Conclusions:
- The SeV-Gag system demonstrates controlled replication and antigen expression in macaques.
- The system is safe for use in primates, eliciting T cell responses with limited viral spread.
- These findings support the potential of SeV-based vaccine systems for use in humans against immunodeficiency viruses.