Development of Pandemic Vaccines: ERVEBO Case Study

Abstract

Preventative vaccines are considered one of the most cost-effective and efficient means to contain outbreaks and prevent pandemics. However, the requirements to gain licensure and manufacture a vaccine for human use are complex, costly, and time-consuming. The 2013-2016 Ebola virus disease (EVD) outbreak was the largest EVD outbreak to date and the third Public Health Emergency of International Concern in history, so to prevent a pandemic, numerous partners from the public and private sectors combined efforts and resources to develop an investigational Zaire ebolavirus (EBOV) vaccine candidate (rVSVΔG-ZEBOV-GP) as quickly as possible. The rVSVΔG-ZEBOV-GP vaccine was approved as ERVEBO^TM by the European Medicines Authority (EMA) and the United States Food and Drug Administration (FDA) in December 2019 after five years of development. This review describes the development program of this EBOV vaccine, summarizes what is known about safety, immunogenicity, and efficacy, describes ongoing work in the program, and highlights learnings applicable to the development of pandemic vaccines.

Keywords: Ebolavirus vaccine; rVSVΔG-ZEBOV-GP; regulatory strategy; vaccine development; vaccine manufacturing.

Figure 1

Timeline of Zaire Ebolavirus vaccine development beginning with Ebolavirus gene introduction into the VSV backbone in the 1980s through the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) approval, WHO prequalification, and approval in African countries in 2019. EMA = European Medicines Agency; EVD = Zaire ebolavirus disease; FDA = United States Food and Drug Administration; NHPs = non-human primates; NLM = National Laboratory of Microbiology; USAMRIID = United States Army Medica Research Institute of Infectious Diseases; VSV = vesicular stomatitis virus; WHO = World Health Organization. Adapted from [7].

Figure 2

End-to-end steps for vaccine manufacturing and supply. The manufacture of a vaccine requires the completion of a sequence of activities starting from the receipt of raw materials and components through the release of a dose that is ready to be administered to a patient. At different steps of the process, inventory (I) may be held until the completion of the preceding step.

Figure 3

Glycoprotein-enzyme-linked immunosorbent assay (GP-ELISA), plaque reduction neutralization test (PRNT), and seroresponse results by study for Partnership for Research on Ebola Virus in Liberia (PREVAIL), Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE), Guinea Front Line Worker (FLW) trial study, lot consistency study, and integrated results. (A): GP-ELISA GMTs (B): PRNT GMTs (C): GP-ELISA seroresponse ≥2-fold and ≥200 EU/mL rise from baseline (D): PRNT seroresponse ≥4-fold rise from baseline.