Lassa fever vaccine use cases and demand: Perspectives from select West African experts
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Cited by 4 publications
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A Lassa virus live attenuated vaccine candidate that is safe and efficacious in guinea pigs
Lassa virus (LASV) is a rodent-borne mammarenavirus that causes tens to hundreds of thousands of human infections annually in Western Africa. Approximately 20% of these infections progress to Lassa fever (LF), an acute disease with case–fatality rates from ≈20–70%. Currently, there are no approved vaccines or specific therapeutics to prevent or treat LF. The LASV genome consists of a small (S) segment that has two genes, GP and NP, and a large (L) segment that has two genes, L and Z. In both segments, the two genes are separated by non-coding intergenic regions (IGRs). Recombinant LASVs (rLASVs), in which the L segment IGR was replaced with the S segment IGR or in which the GP gene was codon-deoptimized, lost fitness in vitro, were highly attenuated in vivo, and, when used as vaccines, protected domesticated guinea pigs from otherwise lethal LASV exposure. Here, we report the generation of rLASV/IGR-CD, which includes both determinants of attenuation and further enhances the safety of the vaccine compared with its predecessors. rLASV/IGR-CD grew to high titers in Vero cells, which are approved for human vaccine production, but did not cause signs of disease or pathology in guinea pigs. Importantly, guinea pigs vaccinated with rLASV/IGR-CD were completely protected from disease and death after a typically lethal exposure to wild-type LASV. Our data support the development of rLASV/IGR-CD as a live-attenuated LF vaccine with stringent safety features.
A Lassa virus live attenuated vaccine candidate that is safe and efficacious in guinea pigs
Lassa virus (LASV) is a rodent-borne mammarenavirus that causes tens to hundreds of thousands of human infections annually in Western Africa. Approximately 20% of these infections progress to Lassa fever (LF), an acute disease with case–fatality rates from ≈20–70%. Currently, there are no approved vaccines or specific therapeutics to prevent or treat LF. The LASV genome consists of a small (S) segment that has two genes, GP and NP, and a large (L) segment that has two genes, L and Z. In both segments, the two genes are separated by non-coding intergenic regions (IGRs). Recombinant LASVs (rLASVs), in which the L segment IGR was replaced with the S segment IGR or in which the GP gene was codon-deoptimized, lost fitness in vitro, were highly attenuated in vivo, and, when used as vaccines, protected domesticated guinea pigs from otherwise lethal LASV exposure. Here, we report the generation of rLASV/IGR-CD, which includes both determinants of attenuation and further enhances the safety of the vaccine compared with its predecessors. rLASV/IGR-CD grew to high titers in Vero cells, which are approved for human vaccine production, but did not cause signs of disease or pathology in guinea pigs. Importantly, guinea pigs vaccinated with rLASV/IGR-CD were completely protected from disease and death after a typically lethal exposure to wild-type LASV. Our data support the development of rLASV/IGR-CD as a live-attenuated LF vaccine with stringent safety features.
Health and economic impacts of Lassa vaccination campaigns in West Africa
Lassa fever is a zoonotic disease identified by the World Health Organization (WHO) as having pandemic potential. This study estimates the health-economic burden of Lassa fever throughout West Africa and projects impacts of a series of vaccination campaigns. We also model the emergence of ‘Lassa-X’—a hypothetical pandemic Lassa virus variant—and project impacts of achieving 100 Days Mission vaccination targets. Our model predicted 2.7 million (95% uncertainty interval: 2.1–3.4 million) Lassa virus infections annually, resulting over 10 years in 2.0 million (793,800–3.9 million) disability-adjusted life years (DALYs). The most effective vaccination strategy was a population-wide preventive campaign primarily targeting WHO-classified ‘endemic’ districts. Under conservative vaccine efficacy assumptions, this campaign averted $20.1 million ($8.2–$39.0 million) in lost DALY value and $128.2 million ($67.2–$231.9 million) in societal costs (2021 international dollars ($)). Reactive vaccination in response to local outbreaks averted just one-tenth the health-economic burden of preventive campaigns. In the event of Lassa-X emerging, spreading throughout West Africa and causing approximately 1.2 million DALYs within 2 years, 100 Days Mission vaccination averted 22% of DALYs given a vaccine 70% effective against disease and 74% of DALYs given a vaccine 70% effective against both infection and disease. These findings suggest how vaccination could alleviate Lassa fever’s burden and assist in pandemic preparedness.
Lassa fever in Nigeria: epidemiology and risk perception
Annual outbreaks of Lassa fever have resulted in a public health threat in Nigeria and other endemic countries in Sub-Saharan Africa. While the Lassa Virus (LASV) is endemic in rodent populations, zoonotic spillover to humans causes annual outbreaks. This study reviewed the burden of Lassa fever (LF) in Nigeria between 2020 and 2023 and conducted a cross-sectional survey of Nigerians to evaluate their risk perceptions of LF. During the period under review, 28,780 suspected and 4,036 confirmed cases of LF were reported from 34 of the 37 states of Nigeria. These cases resulted in 762 deaths (a CFR of 18.9%). The overall case positivity rate was 14% (4,036/28,780), with more positive cases in 2020 (17.5%, n = 1,189/6,791). A total of 2,150 study participants were enrolled in the prospective cross-sectional study, with most of them (87.5%, n = 1,881/2,150) having previously heard of Lassa fever (LF). The numerical scoring system revealed that 35.43% ( n = 762/1,881) of those aware of LF have poor knowledge of its preventive measures, route of transmission, and control measures. Approximately 6.84% ( n = 147/2,150) of them were at a high risk of contracting LF, with 27.6% ( n = 584/2,150) of study participants feeling concerned about contracting LF because of the presence of rodents in their immediate vicinity, occupational exposure to healthcare workers, and the probability of contamination of food by infected rodents without necessary food safety measures. Multivariable logistic regression analysis revealed that tertiary education was associated with an increased likelihood of better LF knowledge (OR: 17.32; 95% CI: 10.62, 28.26; p < 0.01) and a lower risk of contracting LF when compared to respondents with no formal education. In addition, study participants who reside in low-burden states have lower LF perception than those residents in high-LF-burden states (OR: 0.59; 95% CI: 0.38–0.91; p = 0.049). On the other hand, study participants with poor risk perception (knowledge) of LF had a higher likelihood (RR: 0.33; 95% CI: 0.20, 0.53; p < 0.01) of contracting LF when compared to those with good knowledge of LF. Similarly, those residents in low LF burden states were less likely (OR: 0.09; 95% CI: 0.05,0.17; p < 0.01) to contract LF when compared to those residents in high burden states. There is a need to improve LF diagnostics capacity, infection prevention and control measures, and implementation of the One Health approach to controlling LASV from animal reservoirs. In addition, public enlightenment campaigns to address fundamental knowledge gaps are crucial to mitigating the ongoing and future impact of LF in Nigeria. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-78726-3.
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