cAD3-Marburg Vaccine April 2023
The cAD3-Marburg vaccine candidate is being developed by the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health (NIH). This vaccine uses a modified chimpanzee adenovirus, cAD3. cAD3 is not replicable, nor can it infect cells. Instead, it displays a glycoprotein found on the Marburg Virus (MARV) surface to induce immune responses against the virus.
The peer-review journal The Lancet published a study on January 28, 2023, that concluded this first-in-human clinical trial of the cAd3-Marburg vaccine showed the agent is safe and immunogenic, with a safety profile similar to previously tested cAd3-vectored filovirus vaccines. In addition, 95% of participants produced a glycoprotein-specific antibody response four weeks after a single vaccination, which remained in 70% at 48 weeks. RV 507 was a Phase I, open-label study that was a dose escalation of VRC-MARADC087-00-VP, a cAd3 vector vaccine, which encodes wild-type glycoprotein from Marburgvirus.
The NIAID plans to conduct further trials of the cAd3-Marburg vaccine in Ghana, Kenya, Uganda, and the United States. If additional data support the promising results in the Phase 1 trial (Last Update Posted: August 11, 2022), the cAd3-Marburg virus vaccine could be used in emergency responses to MARV outbreaks.
An Albert B. Sabin Vaccine Institute sponsored Phase 2, Randomized, Double-blind, Placebo-Controlled Trial to Evaluate Safety, Tolerability, and Immune Responses of an Investigational Monovalent Chimpanzee Adenoviral-Vectored Marburg Virus Vaccine in Healthy Adults was last updated on April 19, 2023.
The Maryland-based NIAID conducts and supports research at the NIH, throughout the United States, and worldwide to study the causes of infectious and immune-mediated diseases and to develop better means of preventing, diagnosing, and treating these illnesses. Other NIAID-related materials are available on the NIAID website.
cAD3-Marburg Indication
Marburg virus is in the same family as Ebola, causing a rapidly progressive febrile illness that leads to shock and death in many infected individuals. Human outbreaks begin when the virus jumps from the animal host to the human. In sub-Saharan Africa, it is most likely infected bats that infect humans. MARV symptoms are similar to Ebola, including fever, headaches, chills, rash, abdominal pain, vomiting, and diarrhea. As the disease progresses, patients suffer from multiple organ dysfunction, delirium, and significant bleeding from the gastrointestinal tract or other sites that may result in death.
Marburg Vaccine Candidates 2023
Marburg disease protective vaccine candidates are in clinical development, but none have been U.S. FDA-approved.
cAD3-Marburg News 2023
March 22, 2023 - Since the first WHO Disease Outbreak News published on February 25, 2023, eight additional laboratory-confirmed cases of MVD have been reported in Equatorial Guinea.
February 15, 2023 - A news article was published by the journal Nature: Marburg virus outbreak: researchers race to test vaccines.
January 28, 2023 - Marburg vaccine shows promising results in a first-in-human NIH-funded clinical study. The RV 507 trial of this cAd3-Marburg vaccine showed the agent is safe and immunogenic, with a safety profile similar to previously tested cAd3-vectored filovirus vaccines. In addition, 95% of participants produced a glycoprotein-specific antibody response four weeks after a single vaccination, which remained in 70% at 48 weeks.
October 13, 2022 - An introduction to the Marburg virus vaccine consortium, MARVAC.
cAD3-Marburg Clinical Trial 2023
Phase 1 clinical trial enrolled 40 healthy adult volunteers. They received a single dose of either a low dose of the vaccine (1x1010 particle units) or a higher dose (1x1011 particle units). For safety, the volunteers were enrolled in a dose-escalation plan. Three participants received the lower dose. After no severe adverse reactions were observed after seven days, the trial enrolled the remaining 17 volunteers. The same procedure was also used for the higher-dose group. Volunteers were monitored for adverse reactions to the investigational vaccine and evaluated at regular intervals for 48 weeks to track their immune responses.
This is a multicenter, double-blinded, placebo-controlled, Phase II study to evaluate the safety, tolerability, and immunogenicity of a single dose of the cAd3-Marburg vaccine in healthy adults up to 70 years of age in Uganda and Kenya. The study will enroll 125 eligible participants randomized 4:1 to receive the cAd3-Marburg vaccine at 1.0 × 10^11 PU dose or placebo (0.9% sodium chloride (NaCl) solution) at Day 1, intramuscularly in the deltoid muscle. Participants will be screened for eligibility up to 28 days before enrollment. Enrollment will be staggered, starting with healthy adults 18 to 50 (inclusive). Upon enrollment of a minimum of 25 younger adult participants (sentinel), the safety data the independent DSMB will review up to 7 days post-vaccination of these 25 sentinel participants. Progression to enrollment of the older adults (>50 to 70 years of age) will be dependent on the unblinded review of the Data Safety Monitoring Board (DSMB). Safety and immunogenicity will be assessed on Days 1, 8, 15, 29, 85, and 169 and conclude at the end of the study visit on Day 366.
