At Issue

Was it the right decision to introduce a second vaccine in the DRC Ebola outbreak?

For more than a year, only Merck’s investigational V920 vaccine was used in the Ebola outbreak in the Democratic Republic of the Congo, or DRC. The vaccine, which has been shown to be more than 97% effective, can be used as both pre- and post-exposure prophylaxis. In September, WHO confirmed that a second vaccine would be used to help prevent further spread of the virus. Infectious Disease News asked Daniel R. Lucey, MD, MPH, adjunct professor of medicine and infectious diseases at Georgetown University, if introducing the second vaccine was the right decision.

Daniel R. Lucey

Yes, the right decision by the DRC leadership fighting the ongoing Ebola outbreak was announced Sept. 23 by WHO. It stated that a second investigational Ebola vaccine, manufactured by Johnson & Johnson–owned Janssen, would be introduced in “at-risk populations that do not have active Ebola transmission” in the DRC in mid-October. They did not state whether this study will be a phase 2 trial or a phase 3 pivotal efficacy trial. If a phase 3 trial, it is unclear what the comparison arm(s) will be.

Appropriately, this announcement followed the initial 7-point announcement on Sept. 20 from the DRC technical secretariat headed by the renowned DRC Ebola expert, Professor Jean-Jacques Muyembe, in their daily Multisectoral Committee of the Ebola Response (CMRE) update on the epidemic. This second investigational vaccine will be offered to volunteers before any exposure to the Ebola virus, and its implementation will follow DRC ethics committee approval and informed consent. It should be emphasized that this J&J vaccine is not being proposed for use in a post-exposure setting or for contacts of patients with Ebola, the way that the first investigational vaccine, manufactured by Merck, has been used in the DRC since 2018. It is wise of the DRC leadership to define these clear differences between use of the two vaccines in order to avoid confusion about the vaccines among the multiple communities in the DRC.

A crucial difference between the two vaccines is that the J&J vaccine requires two non-identical shots 56 days apart, whereas the Merck vaccine only requires one shot. Thus, it is clear why the J&J vaccine is not being given to contacts of persons with Ebola, a virus with an incubation period of 2 to 21 days. Of note, the first dose of the J&J vaccine includes an adenovirus vector and a glycoprotein antigen only from Ebola Zaire, the species causing the outbreak. The second dose 56 days later includes an MVA vector and several filovirus protein antigens from Ebola (Zaire, Sudan and Tai Forest), as well as from the Marburg virus.

Before the J&J vaccine trial starts, two key issues are worth considering: 1) this vaccine does not contain any antigens from the Ebola Bundibugyo species of the virus; and 2) this vaccine has never been in a phase 3 pivotal efficacy trial in humans, and even the ongoing trial in Uganda of this vaccine is a single-arm phase 2 trial. Thus, from both a scientific and an informed consent perspective, these are important points of clarification with regard to the CMRE daily updates from Sept. 20 and Sept. 23, which indicated that the vaccine would protect against not only Ebola Zaire, but against other species of the virus, including Bundibugyo. Only a phase 3 pivotal efficacy trial in humans can prove any such protection by a vaccine.

Disclosure: Lucey reports no relevant financial disclosures.

For more than a year, only Merck’s investigational V920 vaccine was used in the Ebola outbreak in the Democratic Republic of the Congo, or DRC. The vaccine, which has been shown to be more than 97% effective, can be used as both pre- and post-exposure prophylaxis. In September, WHO confirmed that a second vaccine would be used to help prevent further spread of the virus. Infectious Disease News asked Daniel R. Lucey, MD, MPH, adjunct professor of medicine and infectious diseases at Georgetown University, if introducing the second vaccine was the right decision.

Daniel R. Lucey

Yes, the right decision by the DRC leadership fighting the ongoing Ebola outbreak was announced Sept. 23 by WHO. It stated that a second investigational Ebola vaccine, manufactured by Johnson & Johnson–owned Janssen, would be introduced in “at-risk populations that do not have active Ebola transmission” in the DRC in mid-October. They did not state whether this study will be a phase 2 trial or a phase 3 pivotal efficacy trial. If a phase 3 trial, it is unclear what the comparison arm(s) will be.

Appropriately, this announcement followed the initial 7-point announcement on Sept. 20 from the DRC technical secretariat headed by the renowned DRC Ebola expert, Professor Jean-Jacques Muyembe, in their daily Multisectoral Committee of the Ebola Response (CMRE) update on the epidemic. This second investigational vaccine will be offered to volunteers before any exposure to the Ebola virus, and its implementation will follow DRC ethics committee approval and informed consent. It should be emphasized that this J&J vaccine is not being proposed for use in a post-exposure setting or for contacts of patients with Ebola, the way that the first investigational vaccine, manufactured by Merck, has been used in the DRC since 2018. It is wise of the DRC leadership to define these clear differences between use of the two vaccines in order to avoid confusion about the vaccines among the multiple communities in the DRC.

A crucial difference between the two vaccines is that the J&J vaccine requires two non-identical shots 56 days apart, whereas the Merck vaccine only requires one shot. Thus, it is clear why the J&J vaccine is not being given to contacts of persons with Ebola, a virus with an incubation period of 2 to 21 days. Of note, the first dose of the J&J vaccine includes an adenovirus vector and a glycoprotein antigen only from Ebola Zaire, the species causing the outbreak. The second dose 56 days later includes an MVA vector and several filovirus protein antigens from Ebola (Zaire, Sudan and Tai Forest), as well as from the Marburg virus.

Before the J&J vaccine trial starts, two key issues are worth considering: 1) this vaccine does not contain any antigens from the Ebola Bundibugyo species of the virus; and 2) this vaccine has never been in a phase 3 pivotal efficacy trial in humans, and even the ongoing trial in Uganda of this vaccine is a single-arm phase 2 trial. Thus, from both a scientific and an informed consent perspective, these are important points of clarification with regard to the CMRE daily updates from Sept. 20 and Sept. 23, which indicated that the vaccine would protect against not only Ebola Zaire, but against other species of the virus, including Bundibugyo. Only a phase 3 pivotal efficacy trial in humans can prove any such protection by a vaccine.

Disclosure: Lucey reports no relevant financial disclosures.