For example, the Ad26 vaccine currently undergoing phase 3 trials from Dr. Barouch’s group is a single-shot vaccine, the only one currently in that stage of evaluation. Dr. Barouch noted, “A single-shot vaccine is more convenient and deployable and logistically feasible.” He notes that a two-shot vaccine would likely be more immunogenic and provide greater protection, but it would be less convenient to implement. The group also has a two-shot based vaccine that is expected to enter phase 3 trials.
Ongoing Technical Concerns
At the outset of vaccine development, certain technical questions were prominent, and some of these will continue to need to be addressed.
Safety is obviously a key issue during the vaccine development process and beyond. Especially at the outset, researchers had concerns about the theoretical possibility of antibody-dependent disease enhancement, a phenomenon in which previous virus contact (through natural exposure or via a vaccine) might actually worsen disease outcomes. This phenomenon has been observed in some other viruses and in in certain animal models for the related SARS-1 (SARS-CoV) virus.4 However, Dr. Barouch emphasized that such a safety concern has not emerged in animals or humans from any of the SARS-CoV-2 virus literature to date, which has been reassuring to researchers. However, this will need to be borne out through the results of clinical trials.
The durability of the protection acquired by a vaccine will also be a key point of study, as it is for any vaccine. This is currently not known for any of the vaccine candidates.
Additionally, even though the virus is genetically stable compared to some other viruses, mutations may occur, leading to new virus strains. “As vaccines become implemented, there’s a possibility that there could emerge a variance of the virus that could escape the neutralizing antibody responses induced by the vaccine,” said Dr. Barouch. This would necessitate the development of new vaccines for immunological protection.
Dr. Barouch shared some insights specific to patient populations often seen by rheumatologists. He pointed out that although immunosuppressed individuals are not allowed in the current clinical trials, once a correlate of protection is known, researchers could quickly evaluate whether this population could benefit from a vaccine. He clarified that from a theoretical level, safety isn’t the concern for the vaccine his team developed, as it doesn’t use a live viral vector. “The question is whether the immune response will be blunted in people on immunosuppression,” he noted.
