Rapid protection induced by a single-shot Lassa vaccine in male cynomolgus monkeys

Abstract

Lassa fever hits West African countries annually in the absence of licensed vaccine to limit the burden of this viral hemorrhagic fever. We previously developed MeV-NP, a single-shot vaccine protecting cynomolgus monkeys against divergent strains one month or more than a year before Lassa virus infection. Given the limited dissemination area during outbreaks and the risk of nosocomial transmission, a vaccine inducing rapid protection could be useful to protect exposed people during outbreaks in the absence of preventive vaccination. Here, we test whether the time to protection can be reduced after immunization by challenging measles virus pre-immune male cynomolgus monkeys sixteen or eight days after a single shot of MeV-NP. None of the immunized monkeys develop disease and they rapidly control viral replication. Animals immunized eight days before the challenge are the best controllers, producing a strong CD8 T-cell response against the viral glycoprotein. A group of animals was also vaccinated one hour after the challenge, but was not protected and succumbed to the disease as the control animals. This study demonstrates that MeV-NP can induce a rapid protective immune response against Lassa fever in the presence of MeV pre-existing immunity but can likely not be used as therapeutic vaccine.

A next-generation intranasal trivalent MMS vaccine induces durable and broad protection against SARS-CoV-2 variants of concern

“…One potential concern of using the MMR vaccine platform is the preexisting immunity. Several studies showed that the preexisting MeV immunity had minimal impact on MeV replication and induction of antigen-specific immune responses ( 38 – 40 ). In phase II trial, rMeV-based Chikungunya virus has excellent immunogenicity in the presence of preexisting MeV immunity ( 41 ).…”

Lassa fever vaccine candidates: A scoping review of vaccine clinical trials

“…This vaccine is designed to express the LASV glycoprotein and nucleoprotein antigens, is administered intramuscularly and has no freezing requirements [33]. The measles virus was chosen as a vector as it can stably encode large genome segments and has been shown to contribute to a good immune response [36][37][38][39].…”

Deep mutational scanning reveals functional constraints and antigenic variability of Lassa virus glycoprotein complex

“…29–32 In addition, vaccines that elicit antibodies against GPC are also being developed. 33–37 However, the high variability of GPC (up to ∼8% amino-acid divergence among lineages) raises the specter of antibody and vaccine escape, a problem that has been observed for other viruses—including most recently SARS-CoV-2. 38–41…”

“…[29][30][31][32] In addition, vaccines that elicit antibodies against GPC are also being developed. [33][34][35][36][37] However, the high variability of GPC (up to ~8% amino-acid divergence among lineages) raises the specter of antibody and vaccine escape, a problem that has been observed for other viruses-including most recently SARS-CoV-2. [38][39][40][41] To understand the potential for genetic and antigenic variation in GPC, we used deep mutational scanning 42 to measure how nearly all GPC amino-acid mutations affect cell entry and antibody neutralization in the context of a safe pseudovirus system.…”