RESEARCH BRIEFING – WEEK IN REVIEW
Johnson & Johnson Janssen covid-19 vaccine 85% effective by Day 28 and 100 percent effective by Day 49
Last week, headlines and stories circulated about the Johnson & Johnson (J&J)/Janssen vaccine based on a press release containing data from an interim analysis of their phase 3 clinical trial. The data made public at that time indicate that another weapon against SARS-CoV-2 could soon become available in the United States. This would be particularly helpful in the effort to vaccinate more people, as the J&J vaccine does not require a second booster.
The data released come from the ongoing ENSEMBLE Trial, a randomized, double-blind, placebo-controlled phase 3 study (i.e. meaning that thousands of patients are being enrolled) that assesses the safety and efficacy of vaccine. Unlike the Pfizer/BioNtech and Moderna vaccines, which rely on mRNA technology, the J&J vaccine is a so-called recombinant vector, meaning it uses a modified human adenovirus as a delivery mechanism for the genetic code for the spike protein of SARS-CoV-2.
Importantly, the J&J vaccine is a single dose vaccine as compared to the two currently authorized mRNA vaccines, which require 2 doses of the vaccine three to four weeks apart. Additionally, J&J reports that the "single-dose vaccine candidate is estimated to remain stable for two years at -20°C (-4°F), at least three months of which can be at temperatures of 2-8°C (36°F–46°F)," meaning that unlike the current options, refrigeration will suffice for the last few legs of the journey that any particular lot of the vaccine makes.
The results are impressive. The ENSEMBLE trial enrolled over 43,000 participants ages 18 years and older across three geographic regions, the United States, Latin America, and South Africa. Approximately 1 percent of patients enrolled in the study developed covid-19. The J&J single dose vaccine was 66 percent effective at preventing moderate and severe Covid-19 by day 28 after vaccination among all participants from the above-mentioned regions, including those regions with an emerging viral variant. Protection against SARS-CoV-2 was greatest in the United States (72 percent) and worst in South Africa (57 percent) where potentially more infectious variants have been reported recently. These results are likely to be further confounded by participant exposure to emerging viral variants; nearly 95 percent of all participants who developed covid-19 in South Africa were found to have been infected with SARS-CoV-2 from the B.1.351 lineage. That particular lineage has been found to resist, at least to some degree, antibodies generated by previous infections and other vaccines, as covered in Brief19.
However, with respect to the prevention of severe disease, the J&J vaccine was 85 percent effective across all regions by post-vaccination day 28. But most interestingly, J&J announced that there were no cases of severe covid-19 among participants after post-vaccination day 49. Does this mean the J&J vaccine is 100 percent effective at preventing severe covid-19 by day 49? We will only know that once the full data are released—but it is possible, based on these preliminary reports. In addition, no participants who received the J&J vaccine were either hospitalized for covid-19 nor died 28 days post-vaccination. This implies that one shot and one month of waiting could eliminate the most feared complications of SARS-CoV-2 infection, assuming that new variants do not render these findings obsolete.
Serious adverse events (i.e. side effects) were reportedly rare, with more participants in the placebo group reporting adverse events compared to those who received J&J vaccine. This implies that some of the adverse events reported by patients in the placebo arm may in fact be related to subsequently developing covid-19 itself, rather than as a result of anything in the vaccine or placebo shots themselves. The rates of fever were 9 percent, with Grade 3 fevers (greater than 39°C or 102.1°F) occurring just 0.2 percent of the time.
In light of this release, J&J announced it will file for Emergency Use Authorization in the U.S. in early February with plans to have the vaccine immediately available to ship when authorization is provided. Although these results were announced by press release, so far results from the large vaccine trials have had such impressive results, that even "science by press release" has ended up being borne out by the actual data when subsequently released. We hope the same is true for this vaccine. 2 February 2021.
The US Centers for Disease Control and Prevention released a detailed look at the demographics of those who have received coronavirus vaccinations in the first month of widespread rollouts across the United States. Data was obtained from information reported to the CDC by vaccinators around the country and the findings were published in Morbidity and Mortality Weekly Report (MMWR), the agency's medical journal.
The report covers just under the first 13 million people to receive at least 1 dose of the Pfizer/BioNtech or Moderna covid-19 vaccine, representing just 4 percent of the total US population and 5 percent of the US population 16 years of age or older. Most of the vaccinations have been in persons in the "Phase 1a group," as defined by the CDC's Advisory Committee on Immunization Practices (ACIP). ACIP has recommended priority to healthcare workers and long-term care facility staff and residents.
Thus far, more women (63 percent) have received the vaccine than men. The most vaccinated age group was 50 years and older (55 percent) followed next by those 18-39 years (28 percent). Information on race and ethnicity was known in a little over half of the recipients. A majority of those in whom the race or ethnicity was known have been White, at 60 percent of all recipients. While the White demographic makes up 76 percent of the US population overall, that is not necessarily the breakdown of the regions where vaccine rollout has occurred in the highest numbers. For example, in some regions, disparities have been noted, including in New York City, where just 25 percent of the people vaccinated so far have been Black or Latino, despite the fact that together, these two groups make up around 53 percent of the local population.
The Phase 1a group, which the published data reflect, is estimated to cover around 24 million people. But it is unlikely that 50 percent of the Phase 1a group actually received their first jabs. That's because some places, like Florida and Texas, expanded vaccination to all persons 65 years of age or older, meaning that some people in lower priority groups have been vaccinated ahead of those in higher priority groups.
Regional data reporting under representation of vaccine recipients who are minorities in this first round of vaccination is concerning. Some of the low numbers could be due to a lack of complete data (the race or ethnicity were known in only around 52 percent of those vaccinated so far). Moving forward, the focus of vaccination rollout organizers should be to monitor these data, making sure to track emerging inequalities and to determine to the extent possible the reason for any such finding. Whether lower rates of vaccination are due to lack of access, outreach, or hesitancy will be important to measure so that the necessary policy adjustments are made. 3 February 2021.