Researchers in France published a paper in Nature Communications in March 2023 detailing the results of an investigation into their Lassa fever vaccine candidate. MeV-NP was described in 2021 as providing “sufficient” protection against Lassa fever with just a single dose, between 1 month and 1 year after vaccination.
However, the authors note that due to a “limited dissemination area during outbreaks” and the risks of “nosocomial transmission” it would be useful to develop exposed patients during outbreaks. Thus, in the paper they tested if the “time to protection” could be reduced. Results suggest that although MeV-NP can “induce a rapid protective immune response” against Lassa fever, it “can likely not be used as a therapeutic vaccine”.
The study recognises that Lassa fever, caused by the arenavirus LASV, is a “major public health issue in West Africa” resulting in “thousands of deaths each year”. Unfortunately, “low specificity of early symptoms” means that most cases are confirmed at an “advanced stage”. Thus, there is an “urgent need” for the development of both an effective vaccine and suitable treatments.
In our post on the recent cases in Accra, Ghana, we noted that there are a few collaborations in place to develop vaccine candidates, with WHO ranking Lassa fever in its top priority list of diseases requiring urgent vaccine development. WHO’s target product profile (TPP) for this vaccine demands that it should be safe for all age groups, an ideally confer lasting immunity after a single immunisation.
The authors of the study acknowledge that a “preventative vaccine is preferred over an emergency vaccine” but suggest that the latter would still be “highly valuable” in reducing community or hospital outbreaks.
The vaccine candidate is a recombinant measles virus (MEV) expressing LASV GP and NP of the “prototypic Josiah strain”.
“To improve the immunogenicity of the measles backbone, the vaccine was further engineered to abolish the IFN-antagonist activity of NP.”
Previous research demonstrated that a single shot protected cynomolgus monkeys against the disease, conferring cross-protection against “strains from distant lineages II and VII”, and inducing “long-term immunity”. However, a concern about use in the human population is the “pre-existing immunity against MeV”, which could potentially affect the efficacy of the candidate.
The study explores efficacy, suggesting that the vaccine “fully protects MeV pre-immune cynomolgus monkeys” between 16 to 8 days prior to “lethal infection”.
“This is particularly interesting, as most LASV outbreaks are limited to geographical clusters, for which infected rodents are the amin source of viral dissemination in the human population.”
Thus, a vaccine “capable of rapid protection of an exposed population in an outbreak setting would be highly beneficial”.
The authors note that MeV-NP conferred “comparable protection” in animals that were “naive or pre-immune to MEV”, which supports “no effect of the MeV pre-existing immunity” on its efficacy.
Although this reduced time span is a positive outcome, the vaccine “does not demonstrate therapeutic efficacy in animals vaccinated after challenge”.
“Innate or adaptive immune responses against the MeV vector do not help controlling LASV replication, at least in a therapeutic setup”.
The study shows the efficacy of the vaccine with a “short time to protection” despite this the lack of therapeutic benefit, which offers the possibility of vaccination during an outbreak.
For more on Lassa fever and other disease that particularly affect that African continent, join us for a session with Dr Daniel Bausch at the World Vaccine Congress in Washington next month.