Research ArticleEMERGING INFECTIONS

Vaccines inducing immunity to Lassa virus glycoprotein and nucleoprotein protect macaques after a single shot

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Science Translational Medicine  02 Oct 2019:
Vol. 11, Issue 512, eaaw3163
DOI: 10.1126/scitranslmed.aaw3163

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A vaccine to fight Lassa fever

Thousands of people in Western Africa succumb to Lassa fever each year. Lassa virus infections can in some cases respond to antiviral treatment, but there is no vaccine. Mateo et al. tested three different viral-vectored Lassa virus vaccines in a nonhuman primate model. They compared transcriptomic and proteomic signatures as well as B cell and T cell responses after vaccination. One vaccine using a measles virus vector with Lassa virus glycoprotein and nucleoprotein provided almost sterilizing protection upon a lethal Lassa virus challenge. This vaccine will soon be tested in humans and has the potential to make a major impact on the incidence of Lassa fever.

Abstract

Lassa fever is a major threat in Western Africa. The large number of people living at risk for this disease calls for the development of a vaccine against Lassa virus (LASV). We generated live-attenuated LASV vaccines based on measles virus and Mopeia virus platforms and expressing different LASV antigens, with the aim to develop a vaccine able to protect after a single shot. We compared the efficacy of these vaccines against LASV in cynomolgus monkeys. The vaccines were well tolerated and protected the animals from LASV infection and disease after a single immunization but with varying efficacy. Analysis of the immune responses showed that complete protection was associated with robust secondary T cell and antibody responses against LASV. Transcriptomic and proteomic analyses showed an early activation of innate immunity and T cell priming after immunization with the most effective vaccines, with changes detectable as early as 2 days after immunization. The most efficacious vaccine candidate, a measles vector simultaneously expressing LASV glycoprotein and nucleoprotein, has been selected for further clinical evaluation.

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