A recent article published in the New England Journal of Medicine, on April 28, 2016, presented positive results for a clinical trial for the monovalent chimpanzee adenovirus Ebola vaccine boosted with MVA, showing all the participants to be seropositive for antibodies till 180 days of follow-up after vaccination with the ChAd3 vaccine plus the MVA booster.
A comparison of the study results revealed that both B cell and T cell levels and immune responses were greater in the participants who received the vaccine with a MVA booster compared to the participants who only received the ChAd3 vaccine.
The vaccine is an aqueous, sterile, and buffered solution that includes ChAd3 in single dose vials of 9.1×1014 particle units per milliliter, determined on high performance liquid chromatography.
The vaccine was made from isolating chimpanzee cold virus that does not cause disease in humans. Some genetic material of the chimp cold virus was deleted and genetic material from the Ebola virus was introduced in its place. The modified virus particles when introduced into humans caused the body to produce an Ebola protein belonging to Zaire strain, which is rampant in West Africa right now. The protein presents itself as a foreign particle in the body, causing the immune system to attack it by producing T cells and antibodies and remembering the particle for future reference. The memory can help fight off any future Ebola particles in the body, thus creating a protective shield against potential exposure.
The phase 1 study was conducted in a cohort of 60 healthy adults with their consent, at the Centre for Clinical Vaccinology and Tropical Medicine at the University of Oxford, England, from 2014 to 2015. All of the participants were administered a single dose (priming) of chimpanzee adenovirus 3 (ChAd3) vaccine encoding the surface glycoprotein of Zaire ebolavirus (ZEBOV).
The cohort was divided into three categories. The first group received the dose at 1×1010 viral particles, the second group at 2.5×1010 viral particles, and third group at 5×1010 viral particles.
Ten participants (total thirty) from each group were given an additional booster dosage of modified vaccinia Ankara (MVA) strain, encoding the same Ebola virus glycoprotein of the Mayinga strain, along with Marburg virus species, Sudan Ebola virus and the nucleoprotein of Taï Forest Ebola virus, after three to 10 weeks of priming. Out of the total thirty, 12 received the dose at 3×108 plaque forming units, and 18 received the dose at 1.5×108 PFU.
The main aim of the researchers was to observe the duration — efficacy response of the virus which can be critical in an epidemic. A vaccine with longer durability, when in the start of the epidemic most cases go undetected and occur in geographically disparate areas, would be ideal and is desperately needed right now.
Dr Katie Ewer, one of the chief researchers, and a senior immunologist for the Ebola and pre-erythrocytic malaria vaccine trials at the Jenner Institute, previously said, “Efficacy can only be tested in the context of exposure to the outbreak in West Africa.” Thus Ewer and her team used a study design which took into account this critical aspect.
Two additional groups were than recruited with eight participants each who received priming dosage of chimpanzee adenovirus 3 (ChAd3) vaccine at 2.5×1010 viral particles, and booster shots of MVA at 1.5×108 PFU (after one week of priming) and 1.5×108 PFU (after two weeks of priming), respectively. These two groups were formed to understand the prime-boost interval effects for the vaccine and in an attempt to shorten that interval.
The priming vaccine was manufactured at GlaxoSmithKline and MVA vaccine booster was produced at Fisher BioServices, under the supervision of Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID).
The results after four weeks of immunization showed that ZEBOV-specific antibody responses were at geometric mean titer of 752 and 921 for ChAd3 vaccine and rVSV-ZEBOV vaccine respectively. ZEBOV neutralization activity was also at geometric mean titer of 14.9 and 22.2 respectively.
Virus-specific antibodies and glycoprotein-specific CD8+ T cells, increased by a factor of 12 and 5, respectively, after boosting with the MVA vector. All thirty participants showed an increase in neutralizing antibodies. Virus specific antibodies remained positive for six months after vaccination with ChAd3 in all participants but showed higher levels in people with MVA boosters.
Previously, though many vaccines have shown potential in phase 1 trials, only recombinant vesicular stomatitis virus-based vaccine expressing the surface glycoprotein of Zaire ebolavirus (rVSV-ZEBOV) has shown efficacy in the interim phase 3 trial in Guinea. The results in the human trials of phase 3 for this vaccine provided a unique opportunity to access and compare the results with the current ChAd3 vaccine along MVA booster study as mentioned above.
The study was funded by Wellcome Trust, the United Kingdom Department for International Development, the United Kingdom Medical Research Council, and the United Kingdom National Institute for Health Research Oxford Biomedical Research Center.
GlaxoSmithKline prepared a stockpile of 10,000 doses of the vaccine in preparation of fast tracking of the use of vaccine, in Ebola virus epidemic in West Africa.
Ebola virus epidemic was the worst of in the history of the disease and started in 2013 in West Africa. Though the epidemic is under control right now, flare-ups continue to happen in between. From March 23, 2014, nearly 11,315 cases of deaths have been reported along with total of 28,637 diagnosed cases.
Ebola virus can cause viral hemorrhagic fever, with muscular pain, sore throat, headaches, vomiting, diarrhea, rash, and external and internal bleeding. The disease can kill between 25-90 percent of people who are infected.