- Weeks after Johnson & Johnson announced that their experimental COVID-19 vaccine was in final, Phase 3 testing, the company has paused the study to evaluate an unexplained illness in a study participant.
- AstraZeneca’s late-stage vaccine trial is also still on pause in the U.S. after two cases of a neurological illness arose in its study population.
- Both studies are using adenoviral-vector vaccines, based on a technology that has been studied for over 30 years but has not yet produced a vaccine proven to prevent disease in humans.
Just weeks after Johnson & Johnson (J&J) announced that its COVID-19 Ad26.COV2.S vaccine trial ENSEMBLE had reached the final phase of testing, the company has paused the study after one participant developed an ‘unexplained illness.’1 The company released a statement saying, “Following our guidelines, the participant’s illness is being reviewed and evaluated by the ENSEMBLE independent Data Safety Monitoring Board (DSMB) as well as our internal clinical and safety physicians,”2 According to Mathai Mammen, the global head of Janssen research and development at J&J, “It’s not at all unusual for unexpected illnesses that occur in large studies over their duration.”3
ENSEMBLE is a placebo-controlled, double blind study and it is not yet clear whether the participant received the active vaccine or a placebo. No details have been released about the illness and the company said it would be at least a few days before details are known.
It is not the first indication of potential safety issues associated with J&J’s experimental Ad26.COV2.S vaccine for COVID-19. During phase 2 safety studies, more than half of the participants experienced an adverse reaction. Most were local reactions or mild and transient fevers, but 20 (five percent) volunteers in one of the study groups reportedly developed Grade 3 fevers of over 101.3°F.5 The J&J study is projected to enroll 60,000 people.
This is the Second Pause for a COVID-19 Vaccine Trial
This is the second late-stage vaccine trial to be temporarily suspended due to safety concerns. In early September, AstraZeneca’s Phase 3 COVID-19 vaccine trial was twice paused when two participants developed a serious neurological complication called transverse myelitis.6 Though the first patient is believed to have previously undiagnosed multiple sclerosis, William Schaffner, MD, an infectious disease specialist at the Vanderbilt University School of Medicine in Nashville, Tennessee, is quoted as saying that two neurological incidents “would make any independent reviewer anxious… If I were on that data safety monitoring board, that would give me a chill.”7
That trial has been restarted now in other participating countries including Britain, Brazil, India and South Africa, but remains on hold in the U.S. awaiting results of a U.S. Food and Drug Administration (FDA) investigation. Globally, approximately 18,000 people have received AstraZeneca’s vaccine so far.8
Common Grounds for Both Paused Trials
The J&J and the AstraZeneca vaccines are both adenovirus-based. Adenoviruses are “non-enveloped, double-stranded DNA viruses” that generally cause mild respiratory or gastrointestinal infections like the common cold in humans, though an adenovirus infection can be serious in someone with a compromised immune system or preexisting respiratory or cardiac issues.
Several characteristics are cited as advantages to using an adenoviral vector for delivering a vaccine antigen, including the ability to stimulate both an innate (cell-mediated) and humoral (adaptive) immune system response and because adenoviral vectored vaccines are easy to manipulate genetically.9 Another feature is that the adenovirus itself triggers the vaccine’s inflammatory immune response, so it is not necessary to add an adjuvant to the vaccine to provoke an inflammatory response that stimulates immunity.10 Several of the current frontrunners in the race for a COVID-19 vaccine are using genetically modified adenoviral-vectored vaccine protocols, on the theory that they use a more “tried and true” technology than some of the newer vaccine types, like Moderna’s mRNA vaccine.
However, despite more than 30 years of experience with the advenovirus vector technology, no adenoviral-vector vaccine has yet been shown to be effective in human beings, and the only adenoviral-based vaccine currently in use is a rabies vaccine used in wild animals.11 Other potential drawbacks to the adenoviral-vector vaccines have to do with the way the healthy immune system reacts to adenoviruses in nature. People may not respond appropriately to a vaccine based on a natural virus to which they may have already been exposed. People develop immunity not only to natural adenoviruses but also to the modified adenoviruses used in the vaccine and so may neutralize any boosters given.12
The J&J trial is using “adenovirus 26,” an uncommon human adenovirus in hopes most people will not have been exposed and already developed immunity to it. AstraZeneca is using a chimpanzee virus.13
Both Vaccines Are Part of Operation Warp Speed
Another thing the J&J and AstraZeneca vaccines have in common is that they are both being developed under Operation Warp Speed, the public-private business partnership between government and the pharmaceutical industry aiming to rapidly move an experimental COVID-19 vaccine through the approval and distribution process. Operation Warp Speed has come under fire after an NPR report showed that “at least $6 billion in US funding was awarded to various pharmaceutical companies, including J&J, through a third party, a defense contract management firm. This side-step of the established acquisitions process, which details how federal contracts are to be awarded, allows the awarding process to be kept under wraps.”14
1 Herper M. Johnson & Johnson Covid-19 Vaccine Study Paused Due To Unexplained Illness In Participant. STAT Oct. 12, 2020.
2 Fox M. Johnson & Johnson Pauses Covid-19 Vaccine Trial After ‘Unexplained Illness’. CNN Oct. 13, 2020.
3 Pflanzer LR, Dunn A. Johnson & Johnson Says Pausing Its Coronavirus Vaccine Trials Is ‘Not At All Unusual,’ As Researchers Investigate An Unexplained Illness. Business Insider Oct. 13, 2020.
4 ENSEMBLE study details. 2020.
5 Cáceres M. 20 Volunteers Suffer Serious Reactions to Johnson & Johnson’s COVID-19 Vaccine. The Vaccine Reaction Oct. 5, 2020.
6 Haseltine WA. What The Pause In The Johnson & Johnson And Eli Lilly Covid Drug Trials May Mean. Forbes Oct. 14, 2020.
7 Weise E, Weintraub K. Johnson & Johnson Pauses COVID-19 Vaccine Trial After Unexplained Illness, The Second US Trial Now On Hold. USA Today Oct. 13, 2020.
8 Grady D, Wu KJ, LaFraniere S. AstraZeneca, Under Fire for Vaccine Safety, Releases Trial Blueprints. The New York Times Sept. 19, 2020.
9 Dutta SS. What are Adenovirus-Based Vaccines? News Medical Sept. 17, 2020.
10 Cross R. Adenoviral Vectors Are The New COVID-19 Vaccine Front-Runners. Can They Overcome Their Checkered Past? Chemical & Engineering News May 12, 2020.
14 A 2nd, Phase 3 COVID-19 Vaccine Trial Paused. Medical Daily Oct. 13, 2020.