The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 and subsequent COVID-19 pandemic, and ongoing Ebola and Lassa fever epidemics in western and central Africa demonstrate the urgent need for vaccines and therapeutics against emerging and re-emerging infectious diseases. IAVI has a robust vaccine and antibody pipeline to address such challenges.
IAVI’s emerging infectious diseases (EID) vaccine platform includes four vaccine candidates to prevent diseases of global importance:
- Coronavirus disease 2019 (COVID-19)
- Lassa fever
- Marburg virus disease
- Ebola Sudan virus disease
The urgency for a COVID-19 vaccine is clear, and the U.S. Centers for Disease Control and Prevention has classified viruses that cause the other diseases such as hemorrhagic fever viruses listed above as high-priority agents that pose a risk to national security. They have high case fatality rates, and in addition to being epidemic threats, have potential to be used for bioweapons.
IAVI’s EID vaccine candidates are based on a live, replication-competent recombinant vesicular stomatitis virus (rVSV) vector similar to the technology used to develop Merck’s highly effective Ebola Zaire virus vaccine, ERVEBO®, that was recently approved in 2019 by the European Commission, the U.S. Food & Drug Administration, and, in 2020, regulators in several African countries. See graphic, below.
For IAVI’s rVSV-based coronavirus vaccine candidate (rVSVΔG-SARS-CoV-2), our scientists have replaced the VSV gene coding for the VSV surface protein with a gene coding for the surface protein of SARS-CoV-2. The vaccine candidate is safe in humans when administered intramuscularly and has been produced at scale to support larger future clinical trials.
IAVI is conducting preclinical research on this vaccine candidate to determine if intranasal administration can trigger an immune response in the respiratory tract that prevents infection, given that the approved COVID-19 vaccines lack the durability and the ability to fully block transmission and breakthrough infection. Further, IAVI is responding to the continued evolution of SARS-CoV-2 by including variants of concern in our vaccine constructs and preclinical research.
The Coalition for Epidemic Preparedness Innovations (CEPI) and the European and Developing Countries Clinical Trials Partnership (EDCTP) are the main funders of IAVI’s Lassa fever vaccine program. The U.S. Department of Defense/Defense Threat Reduction Agency is supporting development of IAVI’s Marburg and COVID-19 vaccine candidates. The Biomedical Advanced Research and Development Authority (BARDA) is also supporting IAVI’s Sudan ebolavirus candidate. The Government of Japan has contributed to IAVI’s COVID-19 vaccine program.
IAVI and partner scientist have made a number of important contributions to research of monoclonal antibodies (mAbs) for SARS-CoV-2.
Scientists at IAVI’s Neutralizing Antibody Center at Scripps Research and immunologists at Scripps Research were part of a team that identified antibodies from the blood of recovered COVID-19 patients that are capable of neutralizing SARS-CoV-2, the virus that causes COVID-19. Animals that received the potent neutralizing antibodies were protected against disease after challenge with SARS-CoV-2. The results were published in Science in June 2020.
Additionally, the IAVI Antibody Translational Research Program (ATRP) at the Translational Health Science and Technology Institute (THSTI) in Faridabad, India, became the first group, not only in India, but also in a low- and middle-income country, to formally report the invention of a potent and broadly neutralizing SARS-CoV-2 mAb. The researchers studied several mAbs isolated from a convalescent Indian donor and showed that some of the antibodies, alone or in combination, potently neutralized or maintained activity against a variety of SARS-CoV-2 variants, including Omicron.
The portfolio of mAbs identified by IAVI scientists and their partners has potential for application to COVID-19 prevention and treatment research. The work in India highlights the potential for indigenous monoclonal antibody discovery as a viable source of novel countermeasures that could be further developed as treatment and/or prevention options that meet local needs.