P-C3 A Modified Vaccinia Ankara vector expressing Lassa virus-like particles (MVA-LasVLP) protects mice from lethal challenge with a Lassa-Mopeia reassortant virus

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Abstract

The Lassa-endemic areas of West Africa, including the embattled areas of northern Nigeria have been experiencing more frequent outbreaks of Lassa fever (early 2016 through the summer of 2017). Consequently an international effort has been launched to produce a Lassa vaccine, including a test of the MVA-LASV-VLP (GEO-LM02). The MVA vector has been developed by Dr. B. Moss' lab at NIH in collaboration with GeoVax to deliver a variety of vaccine antigens. The GeoVAX-MVA-HIV-VLP has been used in human trials involving more than 500 participants, it has the capacity to express large recombinant antigens, it elicits robust T and B cell responses, and is relatively safe due to its inability to replicate in mammalian cells. Of all the current Lassa vaccine candidates, GEO-LM02 is the only one that produces VLP in vivo. Our experiments tested the optimum route of vaccination. We used young CBA/J mice that were challenged 2 weeks after vaccination with an intracerebral (ic) dose of a Lassa-Mopeia reassortant virus. Mice were given a single dose of GEO-LM02 by subcutaneous (sc), intraperitoneal (ip), and intramuscular (im) routes. One hundred percent of those given im vaccine survived the lethal challenge, whereas the other routes were slightly less protective. All unvaccinated mice died within 8d post challenge. A second round of experiments confirmed the previous results and demonstrated a robust cell-mediated immunity after a single dose im vaccination. Again 100% of the un-vaccinated mice succumbed to lethal challenge and experienced erosion of their blood-brain-barrier. Subsequent experiments will test the durability of immunity in surviving mice.

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