Reports out of Russia that the country approved a COVID-19 vaccine came with more questions than answers, as some in the rest of the world fretted over the apparently paltry degree of testing. Though the product has not completed phase III trials – human research thus far has involved only two groups of volunteers of 38 people each – Russia President Vladimir Putin is said to have declared Gam-COVID-Vac adequately studied.
Sean Tucker, founder and chief scientific officer of South San Francisco-based Vaxart Inc., wasn’t so sure. “I would probably pass on something that was not in phase III, although I suppose if I was in the Congo in an Ebola outbreak and someone told me [my] chances are better with the vaccine, I might consider it,” he said. He pointed out that he has “very little background [about] what the approval process is in Russia, or anything about this vaccine and its history,” but favors the FDA’s stepwise, cautious guidelines for achieving herd immunity safely and as soon as possible. “I’ll just say that the approach in the U.S. seems like we’re more likely to get there,” he said. Vaxart submitted the IND for its COVID-19 prospect Aug. 10.
Russia’s Putin also said one of his daughters has been vaccinated with Gam-COVID-Vac, which was developed by the Gamaleya Research Institute of Epidemiology and Microbiology in Moscow. The Ministry of Health of the Russian Federation issued registration certificate number LP-006395 for the adenovirus-based vaccine, manufactured by JSC Binnopharm. It’s also known as Sputnik V, a nod to the world’s first satellite, Sputnik, launched by Russia in October 1957 during its space race with the U.S. during the Cold War.
One group of volunteers has been discharged, while the other is held at Sechenov University. In an online press briefing, World Health Organization (WHO) spokesperson Tarik Jasarevic said his group is “in close contact” with Russian health authorities and “discussions are ongoing with respect to possible WHO pre-qualification of the vaccine.” That would require close inspection of the findings available on Sputnik V.
Meanwhile, the U.S. push for a COVID-19 vaccine involves phase III trials that have enrolled about 30,000 people. An editorial by William Haseltine in the June 24, 2020, issue of Scientific American cautioned against rushing efforts for a pandemic solution. “The excitement and enthusiasm for a COVID-19 vaccine by the end of 2020 is both palpable and understandable,” he wrote, but “telescoping testing timelines and approvals may expose all of us to unnecessary dangers.”
Haseltine, founder and former chairman and CEO of Human Genome Sciences Inc., of Rockville, Md. – sold to London-based Glaxosmithkline plc in 2012 for $3.6 billion – pointed to, among other things, the possibility of antibody-dependent enhancement (ADE), a situation where the vaccine makes infection worse. Paris-based Sanofi SA’s dengue vaccine, Dengvaxia, ran into such a problem as recently as 2016. “A safe vaccine, effective for all those at risk, is worth the wait, especially when we have other solutions in hand,” he said, citing the well-known public health measures of voluntary quarantine, testing, mask wearing and hand washing.
The Proceedings of the National Academy of Sciences (PNAS) said ADE’s risk may be overblown. “Some researchers argue that although ADE has received the most attention to date, it is less likely than the other immune enhancement pathways to cause a dysregulated response to COVID-19, given what is known about the epidemiology of the virus and its behavior in the human body,” PNAS said. But that doesn’t mean subjects are out of the woods in terms of safety. Th2 immunopathology may be another hazard, in which a faulty T-cell response triggers allergic inflammation, and poorly functional antibodies that form immune complexes, activating the complement system.
Vaxart’s Tucker said that ADE proved worrisome early in the development of vaccines against SARS, one of the original coronaviruses, but “right now, there’s not, as far as I can tell, anything out there that suggests ADE is a problem with all the vaccines that have been into the clinic at this point.” Th2 immunopathology is “a theoretical threat, because it’s seen with other vaccines. At this point, I’d say the risk is low for most” of the products in development. That’s the case, too, for Vaxart’s platform, which allows for oral recombinant protein vaccines administered using a room temperature-stable tablet rather than an injection. The enterically coated pill deploys a non-replicating adenovirus and “gets ignored by your immune system, but once it gets in [the intestine], it starts making your antigens of choice, whether that’s [COVID-19] or something else. Now you have a specific immune response against that antigen, unlike injected adenovirus where you get a really strong response against the antigen and the vector.” Before starting COVID-19 vaccine work, Vaxart had safely dosed more than 450 subjects using a vaccine prospect based on the same platform.
Vaxart also is taking aim at norovirus, in which two phase I studies have been completed; seasonal influenza, in which a phase II challenge study was recently finished; and respiratory syncytial virus. The firm is also working on its first therapeutic vaccine targeting cervical cancer and dysplasia caused by human papillomavirus types 16 and 18.
Another question to ask with COVID-19, Tucker said, is whether serum antibodies are enough to block the disease – T cells might be necessary, or a mucosal response. Injected vaccines don’t supply much of the latter but Vaxart’s approach does. Data were published in The Lancet earlier this year.
