Research Aims

Predicting the Impact of a Transmissible Vaccine on Lassa Virus Control

Introduction: Lassa virus (LASV) is endemic to West Africa, where it is responsible for causing a potentially severe hemorrhagic fever in humans. The primary reservoir of LASV is the rodent Mastomys natalensis, with transmission to humans occurring through contact with the animal’s contaminated urine, feces, blood, or tissue. According to estimates from the World Health Organization (WHO), LASV is responsible for approximately 300,000 cases of illness and 5,000 deaths annually across West Africa (\cite{AfricaCDCLassaFever}). In Nigeria, a significant outbreak in 2022 resulted in 1,067 confirmed cases and 189 fatalities, yielding a case fatality rate (CFR) of 17.7%. By March 2023, there were 784 confirmed cases and 142 deaths in the country (\cite{Malik2023AnOutbreaks}). Furthermore, the virus has spread westward, notably into Ghana, where a recent outbreak led to 14 confirmed cases, 97 traced contacts, and one death (\cite{LassaUpdate2023}). Lassa fever continues to be a major public health concern, particularly in impoverished communities in West Africa. Its persistent spread westward underscores the critical need for intensified research efforts and the implementation of effective control measures. 

Suggestion: Given the absence of a human vaccine for LASV, current interventions focus on reducing contact between humans and infected animals, either through behavioral changes or through the mass culling of the rodent reservoir. An alternative and promising approach involves the use of transmissible vaccines to rapidly establish immunity within wild animal reservoir populations, thereby reducing the prevalence of the virus (\cite{Nuismer2016EradicatingVaccines}). The key advantage of transmissible vaccines lies in their potential to limit the occurrence of spillover events from rodent reservoirs to human populations while conserving ecological biodiversity. The proposed research seeks to address the urgent need for effective control strategies against LASV in West Africa by evaluating the potential impact of a transmissible vaccine. A prototype transmissible vaccine for LASV has been developed, and the next crucial step involves predicting its efficacy in reducing viral spillover into human populations, particularly in regions such as Western Nigeria and Ghana, where the virus is expanding its range. This objective will be accomplished through the pursuit of the following aims:

Specific Aims:

Aim 1: To quantify the force of spillover into the human population. For a transmissible vaccine targeting the reservoir animal to be effective, most human infection must be derived from spillover.  Work on this objective will develop and parameterize mathematical models that partition the force of infection into components attributable to spillover from the reservoir and direct transmission from other humans. Parameterization will rely on viral sequences collected from rodents and humans in areas of LASV range expansion.

Aim 2: To predict the impact of a transmissible vaccine on the spread of Lassa virus. A prototype transmissible vaccine targeting LASV within its rodent reservoir has now been developed and is undergoing experimental testing. Work on this objective will develop and parameterize mathematical models that predict how well this new vaccine is likely to work within the West African regions where the virus is now expanding its range. Parameterization will use data collected from experimental transmission studies conducted in the laboratory and published studies of reservoir animal ecology.

Aim 3: To assess the long-term ecological and epidemiological impacts of the transmissible vaccine. Beyond immediate effects on reducing viral prevalence, it is crucial to assess the long-term ecological and epidemiological impacts of deploying a transmissible vaccine. This objective will use agent-based and ecological modeling approaches to evaluate potential outcomes, including changes in rodent population dynamics, viral evolution, and the vaccine’s potential to alter pathogen-host interactions in the ecosystem. Data will be integrated from field observations, ecological studies, and pathogen evolution models to provide robust forecasts.

Expected Outcomes: The research is expected to generate valuable insights into the potential efficacy and ecological consequences of using a transmissible vaccine to control LASV within its rodent reservoir. From Aim 1, we anticipate identifying the relative contributions of spillover and human-to-human transmission in LASV outbreaks, which will help to establish the appropriate scope for vaccine interventions. Aim 2 is expected to produce predictive models that demonstrate how the vaccine could reduce LASV prevalence and transmission in key regions of West Africa. Aim 3 will provide a comprehensive understanding of the long-term ecological and evolutionary impacts of the vaccine, ensuring that it can be deployed without adverse effects on biodiversity or viral evolution. Overall, the proposed work will inform policy decisions regarding the use of transmissible vaccines as a sustainable and ecologically responsible control measure for LASV.