Immunology and evolvement of the adenovirus prime, MVA boost Ebola virus vaccine

• The first successful primate Ebola vaccine employed a heterologous prime-boost genetic vaccine.
• Single-shot, rapid protection correlates with serum anti-GP IgG in macaques.
• Uniform protection requires rAd vectors that generate effector memory (IFNγ/TNF++) CD8+ T cells.
• Durable protective memory requires additional CD8+ T cells that coexpress IFNγ, TNF, and IL-2.
• The extensive Phase I trial history of rAd-based vaccines expedited Phase III trials in West Africa.

The 2014 Ebola virus outbreak caused an order of magnitude more deaths in a single outbreak than all previous known outbreaks combined, affecting both local and international public health, and threatening the security and economic stability of the countries in West Africa directly confronting the outbreak. The severity of the epidemic lead to a global response to assist with patient care, outbreak control, and deployment of vaccines. The latter was possible due to the long history of basic and clinical research aimed at identifying a safe and effective vaccine to protect against Ebola virus infection. This review highlights the immunology, development, and progress of vaccines based on replication-defective adenovirus vectors, culminating in the successful launch of the first Phase III trial of an Ebola virus vaccine.