Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia

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Abstract

<p class="first" id="d8956342e262">The safety and efficacy of vaccines to prevent Ebola virus disease (EVD) were unknown when the incidence of EVD was peaking in Liberia. </p>

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Most cited references 9

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Harnessing the beneficial heterologous effects of vaccination.

Helen S. Goodridge, S. Sohail Ahmed, Nigel Curtis … (2016)

Clinical evidence strongly suggests that certain live vaccines, in particular bacille Calmette-Guérin (BCG) and measles vaccines, can reduce all-cause mortality, most probably through protection against non-targeted pathogens in addition to the targeted pathogen. The underlying mechanisms are currently unknown. We discuss how heterologous lymphocyte activation and innate immune memory could promote protection beyond the intended target pathogen and consider how vaccinologists could leverage heterologous immunity to improve outcomes in vulnerable populations, in particular the very young and the elderly.

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The effect of dose on the safety and immunogenicity of the VSV Ebola candidate vaccine: a randomised double-blind, placebo-controlled phase 1/2 trial.

Angela Huttner, Julie-Anne Dayer, Sabine Yerly … (2019)

Safe and effective vaccines against Ebola could prevent or control outbreaks. The safe use of replication-competent vaccines requires a careful dose-selection process. We report the first safety and immunogenicity results in volunteers receiving 3 × 10(5) plaque-forming units (pfu) of the recombinant vesicular stomatitis virus-based candidate vaccine expressing the Zaire Ebola virus glycoprotein (rVSV-ZEBOV; low-dose vaccinees) compared with 59 volunteers who had received 1 ×10(7) pfu (n=35) or 5 × 10(7) pfu (n=16) of rVSV-ZEBOV (high-dose vaccinees) or placebo (n=8) before a safety-driven study hold.

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Trained innate immunity as underlying mechanism for the long-term, nonspecific effects of vaccines.

Bastiaan Blok, Rob Arts, Reinout van Crevel … (2015)

An increasing body of evidence shows that the innate immune system has adaptive characteristics that involve a heterologous memory of past insults. Both experimental models and proof-of-principle clinical trials show that innate immune cells, such as monocytes, macrophages, and NK cells, can provide protection against certain infections in vaccination models independently of lymphocytes. This process is regulated through epigenetic reprogramming of innate immune cells and has been termed "trained immunity." It has been hypothesized that induction of trained immunity is responsible for the protective, nonspecific effects induced by vaccines, such as BCG, measles vaccination, and other whole-microorganism vaccines. In this review, we will present the mechanisms of trained immunity responsible for the long-lasting effects of vaccines on the innate immune system.