First ever Lassa fever vaccination with novel candidate begins in Liberia

IAVI, a nonprofit scientific research organisation, has announced that volunteers at the PREVAIL clinical trial site at Redemption Hospital (RH) in Monrovia, Liberia, have been vaccinated with IAVI’s novel vaccine candidate against Lassa fever virus (LASV) in a Phase I clinical trial, named IAVI C102, supported by the Coalition for Epidemic Preparedness Innovations (CEPI).

LASV causes significant yearly outbreaks of an acute viral illness called Lassa fever, which is endemic, or consistently present, in many parts of West Africa. Outbreaks in Guinea, Liberia, Nigeria, Sierra Leone, South Africa, and Togo have resulted in nearly 6,000 suspected cases and more than 180 deaths since early 2022, according to reports by the World Health Organisation (WHO).

The WHO also reported three recently confirmed cases and one death from Lassa fever in the United Kingdom (U.K). No vaccine for LASV is currently available. An estimated 300,000 to 500,000 Lassa fever cases are reported yearly, resulting in approximately 5,000 deaths. However, the true disease burden is currently unknown, and efforts are ongoing to provide a more accurate estimate of disease incidence.

The IAVI-sponsored trial is part of the existing partnership with CEPI, launched in 2018, providing up to US$61.7 million to support IAVI and a global consortium of partners to advance IAVI’s LASV vaccine candidate through Phase I and II clinical trials. CEPI’s ultimate goal, as part of its plan to minimise or even eliminate the risk of future epidemic and pandemic threats, is to produce a licensed Lassa vaccine for routine immunisation.

Clinical evaluation of IAVI’s LASV vaccine candidate is also supported by the Partnership for Research on Vaccines and Infectious Diseases in Liberia (PREVAIL), a Liberia-U.S. clinical research collaboration established in 2014 by the U.S. National Institute of Allergy and Infectious Diseases (NIAID) and the Ministry of Health in Liberia. In 2015, PREVAIL participated in a clinical trial (PREVAIL 1) of Merck’s now-licensed Ebola Zaire vaccine ERVEBO, which uses the same recombinant vesicular stomatitis virus (VSV) vector backbone as the candidates in IAVI’s emerging infectious diseases (EIDs) vaccine development portfolio, including the IAVI LASV vaccine candidate being evaluated in C102.

IAVI C102 (PREVAIL 12) is designed to evaluate the vaccine candidate’s safety, tolerability, and ability to elicit an immune response against Lassa fever among approximately 100 healthy adults in the U.S. and Liberia. Vaccinations have already begun at the Brigham and Women’s Hospital, East-West Medical Research Institute, and George Washington University School of Medicine and Health Sciences in the U.S. Each participant will receive at least one dose of either the study product or placebo and will be monitored for safety for up to one year following vaccination.

IAVI and CEPI are united in their commitment to global equitable access to vaccines, with IAVI’s LASV vaccine candidate to be accessible to all populations that need it, should it be found safe and efficacious in clinical testing. Following IAVI C102, a Phase II trial of the vaccine candidate is also planned in partnership with CEPI, with funding already announced by CEPI and the European & Developing Countries Clinical Trials Partnership (EDCTP) for a Phase IIb trial in West Africa.

To better inform the design of future late-stage Lassa vaccine trials, CEPI has initiated Enable, the largest-ever Lassa fever research programme launched to increase knowledge of the disease burden across West Africa.

Much of the research and development on IAVI’s rVSV platform is performed at the IAVI Vaccine Design and Development Lab (DDL) in Brooklyn, New York. The DDL is located at the bioscience centre in the historic Brooklyn Army Terminal. Since its founding in 2008, the IAVI DDL has become one of the world’s leading viral vector vaccine research and development labs, known for innovation and the generation of novel vaccine design concepts.

IAVI’s LASV vaccine candidate was manufactured by Batavia Biosciences in Leiden, The Netherlands, a contract-development and manufacturing organisation focused on delivering sustainable, low-cost manufacturing solutions in the field of infectious disease and cancer. Through its partnership with Batavia, IAVI intends to develop an end-to-end platform for flexible, low-cost production of epidemic preparedness vaccines.

Scientists with IAVI’s Human Immunology Laboratory at Imperial College London validated the key laboratory tests, or assays, needed to measure immune responses in IAVI C102 and conducted technology transfer of these assays to scientists at RH. Additional critical assay work will be conducted by Scripps Research; Tulane University; Viral Hemorrhagic Fever Consortium; The Ragon Institute of MGH, MIT and Harvard; and the Center for Infectious Disease Research.

Results from IAVI C102 are expected in 2023 and will be made available through open-access publications and via scientific meetings to ensure all can benefit from the research.

RH is part of the National Public Health Institute of Liberia (NPHIL). NPHIL was created in response to the Ebola epidemic in West Africa in 2014-2016. Some of the key goals of the NPHIL include disease surveillance and response and improving epidemic preparedness.

The Liberian Ministry of Health and the U.S. Department of Health and Human Services (through the National Institute of Allergy and Infectious Diseases) agreed to establish PREVAIL in 2014 to conduct clinical research on Ebola therapeutics and vaccines. PREVAIL has since expanded to address other diseases of public health importance in Liberia.

Lassa fever is caused by Lassa fever virus, an emerging zoonotic virus that can cause a range of symptoms in humans, including haemorrhage, vomiting, swelling of the face, and pain in the chest, back, and abdomen. Lassa fever virus is most commonly transmitted to humans from an infected rodent known as the multimammate rat (Mastomys natalensis). However, the virus can also spread from person to person via bodily fluids.

LASV also has the potential to spread more widely if infected individuals, travel and become ill outside the endemic region. The WHO has identified the Lassa fever virus as one of the top emerging pathogens likely to cause severe outbreaks in the near future in its Research and Development Blueprint for Action to Prevent Epidemics.