Abstract
Pichinde virus (PICV) is a bisegmented enveloped RNA virus that targets macrophages and dendritic cells (DCs) early in infection and induces strong innate and adaptive immunity in mice. We have developed a reverse genetics system to produce live recombinant PICV (strain P18) with a trisegmented RNA genome (rP18tri), which encodes all four PICV gene products and as many as two foreign genes. We have engineered the vector to express the green fluorescent protein (GFP) reporter gene (abbreviated as G in virus designations) and either the hemagglutination (HA [H]) or the nucleoprotein (NP [P]) gene of the influenza A/PR8 virus. The trisegmented viruses rP18tri-G/H and rP18tri-G/P showed slightly reduced growth in vitro and expressed HA and NP, respectively. Mice immunized with rP18tri-G/H were completely protected against lethal influenza virus challenge even 120 days after immunization. These rP18tri-based vectors could efficiently induce both neutralizing antibodies and antigen-specific T cell responses via different immunization routes. Interestingly, the immune responses were significantly increased upon a booster dose and remained at high levels even after three booster doses. In summary, we have developed a novel PICV-based live vaccine vector that can express foreign antigens to induce strong humoral and cell-mediated immunity and is ideal for a primeand- boost vaccination strategy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2551-2560 |
| Number of pages | 10 |
| Journal | Journal of virology |
| Volume | 90 |
| Issue number | 5 |
| DOIs | |
| State | Published - 2016 |
Bibliographical note
Funding Information:HHS|NIH| National Institute of Allergy and Infectious Diseases (NIAID) provided funding to Yuying Liang under grant numbers R01AI083409 and R21AI094133. HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) provided funding to Hinh Ly under grant number AI093580.
Publisher Copyright:
© 2016, American Society for Microbiology.
