Evaluating vectors for the design of a spillover-disrupting Lassa virus transmissible vaccine

Lassa fever is a viral zoonotic disease that sickens tens of thousands of people each year when it spills over from its rodent reservoir throughout West Africa. Despite the burden this persistent spillover places on public health, stopping it has proven to be an intractable challenge despite decades of investment and effort. A revolutionary solution is the development of a transmissible vaccine that can spread through the rodent population resulting in immune coverage sufficient to eliminate Lassa virus transmission. Here, we evaluate the feasibility of a transmissible vaccine constructed from native cytomegaloviruses (CMVs) previously isolated from the natural reservoir of Lassa virus, Mastomys natalensis. Using a combination of field sampling, large-scale CMV genome characterization, and mathematical models parameterized using Bayesian methods, we quantified transmission rates and interactions among viruses in northern Sierra Leone. The results demonstrate that two of the three previously isolated CMVs co-infect freely and have R0 values consistent with autonomous elimination of Lassa virus from its rodent reservoir. These results set the stage for the development of a CMV vectored transmissible vaccine that could stop the spillover of Lassa virus throughout West Africa.