Detailed phase 1/2a study findings published in the NEJM on Wednesday showed that all volunteers given Johnson & Johnson’s single-dose coronavirus vaccine Ad26.COV2.S had detectable neutralizing antibodies by day 57. In September, the company reported a preview of the interim results indicating that the vaccine, also known as JNJ-78436735, was “well tolerated and highly immunogenic” at the dose level of 5×1010 viral particles (vp), which was selected for further testing in the ongoing phase 3 ENSEMBLE trial, where a preliminary data readout is anticipated by the end of this month.
In the phase 1/2a study, participants were randomized to receive Ad26.COV2.S at the 5×1010 vp and 1×1011 vp dose levels, or placebo. The vaccine was administered intramuscularly either as a single dose or two doses given eight weeks apart in healthy adults, with 405 enrolled in the 18-to-55 age group and another 405 who were over 65 years.
Titers ‘stable’ for at least 71 days
As previously reported, neutralizing antibody titers against COVID-19 were detected in over 90% of participants after a single vaccination at day 29. The new data showed that among younger adults aged 18 to 55 years, this increased to 100% at day 57, regardless of vaccine dose or age group, while titers then remained stable until at least day 71, which is currently the latest available time point in the ongoing study. Meanwhile, a second dose of Ad26.COV2.S provided an increase in the titer by a factor of 2.6 to 2.9, researchers said. Johnson & Johnson noted that data on durability of immune responses in trial participants aged over 65 years after day 29 will be shared in late January.
The company previously reported that the vaccine had elicited T-cell responses as well. According to the findings detailed in the NEJM, on day 14, CD4+ T-cell responses were detected in 76% to 83% of participants in the 18-to-55 age group and in 67% of those over 65, “with a clear skewing toward type 1 helper T cells,” researchers said. They noted that CD8+ T-cell responses were “robust” overall, but were lower in the 65-plus group.
One vaccine-related serious AE
The interim analysis also revealed that local and systemic reactions to the vaccine either occurred on the day of immunization or the next day, and typically resolved within 24 hours, while the most common adverse events (AEs) were fatigue, headache, myalgia and injection-site pain. However, there were five serious AEs in the study, including a case involving a volunteer who visited the hospital for a fever that was associated with vaccination, although the person recovered within 12 hours. The other AEs were deemed unrelated to Ad26.COV2.S. Johnson & Johnson noted that reactogenicity was lower in the older age group, and was also lower after the second dose.
The company reiterated that if the single-dose vaccine is shown to be safe and effective in the ENSEMBLE trial, it plans to file for FDA emergency-use authorization “shortly afterwards,” while other regulatory applications around the world would follow. Operation Warp Speed chief advisor Moncel Slaoui expressed hope that Johnson & Johnson’s candidate would show effectiveness of 80% to 85%, a rate he said should be sufficient for the US regulator to give its okay. Meanwhile, one top EU official expects that the first doses of the vaccine will be delivered in Europe in April.
Reported production hurdles
However, a report in The New York Times Wednesday indicated that Johnson & Johnson will most likely not be able to provide as many doses this spring as it promised the US government because of unforeseen manufacturing delays. In the company’s $1-billion US contract, Johnson & Johnson pledged to have 12 million doses of its vaccine ready by the end of February, ramping up to a total of 100 million by the end of June. The report, citing anonymous sources, said the company has now fallen as much as two months behind the original production schedule and will not be able to catch up until the end of April, when it was supposed to have delivered more than 60 million doses. Johnson & Johnson also has separate supply deals with the UK and EU.