Modeling optimal deployment strategies for Nipah vaccines and monoclonal antibodies

Nipah virus (NiV) is endemic in Pteropus bats across South and Southeast Asia. Spillover into human populations results in usually fatal disease with the potential for human-to-human spread, which has led to NiV being classified by WHO as a priority pathogen. NiV vaccines and monoclonal antibodies (mAbs) are in development. However, it remains unclear how these medical countermeasures could be used most effectively. Here, we consider three different outbreak scenarios: limited, short-lived outbreaks as seen almost annually in Bangladesh and India; livestock amplified outbreaks as seen in Malaysia in 1998; and a third theoretical scenario of an extended outbreak cause by an evolved NiV strain with increased transmissibility. For each scenario, we considered the potential impact of a vaccine when distributed through either proactive or reactive campaigns, with a hypothetical single-dose vaccine providing 90% protection against infection. We found that, in limited scenarios, the rare nature of spillovers means proactive vaccination would have a limited impact (0.21 deaths [95%CI: 0.08-0.43] averted per 10,000 doses over 30 years) and require 1.2 million doses. Reactive vaccination would also have a limited impact (0.27 deaths [95%CI: 0-2.75] averted per 10,000 doses over 30 years, 31,000 doses required, equivalent to 0.9 deaths [95%CI: 0-1] averted overall) due to the limited number of transmission generations. The use of a stockpile of 10,000 therapeutic mAb regimens that could prevent death in hospitalized patients could increase impact to 49 deaths (95%CI: 23-87) averted over 30 years. Reactive campaigns were the most effective in livestock-amplified outbreaks (2.2 deaths [95%CI: 1.6- 3] averted per 10,000 doses, 630,000 doses used in total) and extended outbreaks (467 deaths [95%CI: 293-463] averted per 10,000 doses, 690,000 doses used in total) but were highly dependent on delays to vaccine delivery. These findings suggest mAbs as the most impactful medical countermeasure under current epidemiology, with vaccines playing a significant role to limit the burden from NiV in livestock amplified and in theoretical extended outbreaks. However, the impact of both medical countermeasures will rely heavily on rapid distribution.