On Friday, pharmaceutical company Johnson & Johnson reported successful results of its phase 3 clinical trial of a coronavirus vaccine developed in the lab of Harvard Medical School Professor Dan Barouch at Beth Israel Deaconess Medical Center (BIDMC). The announcement also, however, fueled concerns over the growing number of virus variants and the continuing effectiveness of available vaccines.
Overall efficacy of the J&J vaccine was 66 percent worldwide (above the FDA threshold for a vaccine to be widely deployed), compared with 90 percent and 95 percent of approved treatments by Pfizer-BioNTech and Moderna. But comparison is difficult because the first two vaccines were tested before the emergence of variant viruses, some of which appear somewhat resistant to treatments.
The J&J vaccine is based on a different technology from currently approved RNA vaccines, using a neutralized adenovirus to deliver DNA containing instructions for the coronavirus’ spike protein into the body. That causes the body to produce spike protein and generates an immune response that protects against the coronavirus. The single-dose vaccine, robust enough to be stored at higher temperatures than RNA vaccines, is thought to be an important addition to the vaccine arsenal and suitable for distribution in rural areas and developing nations, which may be far from deep freezers needed to store RNA vaccines.
The trial showed strong protection against severe disease, hospitalization, and death from COVID-19, with lesser protection against moderate-to-severe disease and lower protection still against moderate-to-severe disease caused by the variant widespread in South Africa, where a portion of the trial was held. The trial showed that 28 days after vaccination, the vaccine protected against moderate-to-severe COVID-19 with 72 percent efficacy in the U.S., 66 percent efficacy in Latin America, and 57 percent efficacy in South Africa, where a variant that spreads more easily and has shown some ability to escape immune responses is widespread. The vaccine’s protection was stronger against severe disease, with 85 percent protection in all regions at 28 days, rising to 100 percent effectiveness — no cases of severe disease — at 49 days. It also showed complete protection against hospitalization and death at 28 days and no allergic reactions in those who received it.
The trial was funded by the federal government’s Biomedical Advanced Research and Development Authority (BARDA) and the National Institutes of Health.
The Gazette spoke with Barouch, who is the William Bosworth Castle Professor of Medicine and director of BIDMC’s Center for Virology and Vaccine Research, about the trial results, the potential for improved results after a second dose, and his thoughts about the ever-changing pandemic.
GAZETTE: Several numbers emerged from the trial: the vaccine’s 72 percent efficacy in the U.S., its 66 percent efficacy globally, and 57 percent in South Africa. There’s also its 85 percent efficacy against severe disease. What do you think is the most significant finding?
BAROUCH: I think the most significant finding is the ability of the vaccine to protect against severe disease, hospitalizations, and deaths, not just in the United States, but throughout the world.
GAZETTE: And that would be 85 percent protection?
BAROUCH: Eighty-five percent protection against severe disease and 100 percent protection against hospitalizations and death.
GAZETTE: And the protection against severe disease improved over time, through day 49?
BAROUCH: Yes, absolutely. We start to see protection as early as week two, but the immune responses are not fully developed by then. So, it’s natural to see protection get better by week four following vaccination, or even later, but some protection is evident as early as two weeks after vaccination.
GAZETTE: How concerning is the lower efficacy in the South Africa results?
BAROUCH: We’ve learned over the last month that there are viral variants that have emerged and actually are now the dominant population of viruses in South Africa, [where] over 95 percent of circulating viruses are a variant that shows partial resistance to antibodies. So we were very concerned about whether we would see any efficacy at all in South Africa and seeing — it was actually 89 percent efficacy against severe disease in South Africa — [it] was really an astonishing result. We’re very happy about that because it shows that at least this vaccine now has proven efficacy against not just the virus that has been circulating, but also the new variants that are partially resistant and are already present in the United States and are dominant viruses elsewhere.
GAZETTE: Are there any implications of that finding about the South Africa variant for other variants that are also circulating?
BAROUCH: We know that there are different variants circulating in Brazil, in South Africa, in the United States, as well as a new variant in California, and probably many others that we don’t know about. And the vaccine showed very robust protection against severe disease in all geographic regions studied.