How a new vaccine candidate could outpace Lassa fever's deadly grip

Nearly 1 in 5 people who test positive for Lassa fever in Nigeria die. The disease continues to be a disease of public health concern in many West African countries and has been on the World Health Organization’s list of priority pathogens for which there is an urgent need for accelerated research and development and countermeasures since 2016. According to WHO, Lassa fever is endemic in Nigeria, Benin, Ghana, Guinea, Liberia, Mali, Sierra Leone, and Togo, but could exist in other West African countries. In these countries, late detection, nonavailability of approved drugs and lack of Lassa fever-specific prevention measures continue to limit the potential of public health interventions. But an approved vaccine could be a game-changer. In April, the inaugural Phase 2 Lassa fever vaccine clinical trial officially commenced in Nigeria. Supported by CEPI, the Coalition for Epidemic Preparedness Innovations and the International AIDS Vaccine Initiative, or IAVI, it is the most advanced Lassa vaccine trial to date. Richard Hatchett, CEO of CEPI, said it represents “an important milestone in public health and signals that better tools to manage and prevent outbreaks are coming.” The world urgently needs a Lassa vaccine for routine immunization, Hatchett added in a press release. Lessons from Ebola Lassa fever shares several striking similarities with Ebola, another deadly viral hemorrhagic fever that has caused outbreaks in West Africa. Both diseases present with initial flu-like symptoms such as fever, muscle aches, and headaches, often leading to delayed recognition and treatment. Furthermore, both viruses are zoonotic in origin, with Lassa fever carried by rodents and Ebola linked to bats. The diseases also share modes of transmission, spreading through direct contact with bodily fluids of infected individuals. It is therefore not surprising that the technologies that were leveraged in the development of vaccines for Ebola are now being used for the vaccine candidate against Lassa fever. Developed by IAVI, the Lassa fever vaccine candidate uses the same platform — the recombinant vesicular stomatitis virus, or rVSV, vector platform — as Merck’s single-dose vaccine against the Ebola virus, which is now licensed in North America, Europe, and 10 African countries. During the 2014-2016 Ebola outbreak in West Africa that especially affected Guinea, Sierra Leone, and Liberia, the Merck team that worked on the vaccine included IAVI President and CEO Mark Feinberg and Swati Gupta, IAVI’s vice president and head of emerging infectious diseases and epidemiology. “When Merck decided that they were not going to work further on the platform, that technology was given back to the Public Health Agency of Canada, who originally developed it, and then we licensed it from them,” Gupta told Devex. “That technology is now being used at IAVI for Lassa fever, Marburg, Sudan Ebola virus. They are at different stages of development.” The need for a vaccine As of July 7, 2024, Nigeria recorded 7,122 suspected and 933 confirmed cases of Lassa fever for the year, with 163 confirmed deaths. This is higher than the same period in the previous year when there were 5,650 suspected and 842 confirmed cases, and 165 deaths. Promoting good hygiene practices is currently the main prevention measure for Lassa fever. But the presence of health workers among the confirmed cases indicates the need for additional prevention tools. In 2024 alone, 33 health workers tested positive for the disease. Yetunde Abioye, Lassa fever focal person at the Nigeria Centre for Disease Control and Prevention, or NCDC, told Devex current prevention measures are still limited to raising awareness and making water, handwashing resources, and personal protection equipment more accessible. In addition to these measures, Abioye added that the health-seeking practice in communities also needs to be considered. “They will first of all take paracetamol. After a long period that they are not seeing any changes, they will then switch to treating malaria, thus wasting critically important time that could make a lot of difference in prognosis,” Abioye told Devex. While noting the difference that a Lassa fever vaccine could make in Nigeria’s fight against the disease, Abioye said that the ideal vaccine candidate should be able to protect people at risk of Lassa fever from coming down with the disease — whether they’ve been previously exposed to the virus or not. Clinical trials underway Abdulwasiu Bolaji Tiamiyu, clinical research center director at HJF Medical Research International and the principal investigator for the clinical trial, told Devex that securing regulatory approval from Nigeria’s National Agency for Food and Drug Administration initially slowed down the trial. But with the approval secured, the trial is now progressing. Overall, the Phase 2 trial is targeting a total sample size of 620 participants across three countries in West Africa — Nigeria, Ghana, and Liberia — with 310 participants expected to be enrolled in Nigeria. The trial will use an age de-escalation approach, starting with older age groups and gradually moving down to younger age groups like adolescents and children. The trial is focused on assessing the safety and ability to trigger an immune response of the vaccine, with multiple layers of quality control and regulatory oversight to ensure adherence to best practices. “The goal is to complete enrollment by the first quarter of 2025 — meaning we would have vaccinated all that we need to vaccinate from Nigeria. The participants are willing, the product is ready and well-kept," Tiamiyu said. In May the Phase 2 clinical trial for the Lassa fever vaccine commenced in Liberia where 204 participants are expected to be recruited at the JFK Hospital in Monrovia’s Montserrado County. Beyond the trials, researchers also want to determine who is at risk for the disease — which could vary from one country to another — to determine the demand and the need for the vaccine. Gupta said IAVI is working with some of its partners in countries where active cases of Lassa fever are recorded each year. “In Nigeria which records cases annually and has areas with high incidence of Lassa fever, it’s possible that there could be some sort of geographical or regional vaccination strategy,” Gupta said. “Elsewhere, a country might choose to vaccinate its healthcare workers or certain high-risk groups even though they are not seeing much cases — but they know that the rodent vector exists in the country, some of which may be infected.” She said a demand forecast, upon which vaccine production would be based, would then be built from their engagement with West African health experts. Gupta believes that a prophylactic vaccination strategy, in addition to a reactive strategy, could be beneficial in this regard. “The idea would be that you would define upfront who would be vaccinated prophylactically in advance, so that, you know, there's a certain core group of people that are at highest risk that we know are protected,” she said. Then where there is an outbreak, supplementary vaccinations can be carried out. “We believe that you could use it both ways. Immunity develops quite rapidly and the vaccine is preventative. It's not going to be used for people who have already developed the disease, but when we see cases starting to come into the hospital, the vaccine could be used to vaccinate around those cases to prevent future infections, future disease,” Gupta said.