For close to 17 million Americans vaccinated with Johnson & Johnson's Janssen COVID-19 vaccine, new data from the Omicron variant wave is renewing questions over its effectiveness as federal officials weigh a new round of booster shots.
While offering less protection than the peaks reached by the widely-used mRNA vaccines produced by Moderna or Pfizer and BioNTech, Johnson & Johnson has long pointed to studies suggesting its vaccine offers more "durable" protection than its competitors.
For example, one recently published study from Johnson & Johnson's scientists estimated the vaccine's effectiveness against hospitalization was 81% through the Delta variant wave and was "stable for at least 180 days after vaccination."
That was similar to the estimate reached by researchers in New York through August 2021 who found the effectiveness of the mRNA shots appeared to be waning in some, but Johnson & Johnson's were not.
During the Omicron wave, Johnson & Johnson released research from South Africa suggesting the shot was 85% effective against COVID-19 hospitalizations.
Multiple outlets also pointed to data gathered by the Centers for Disease Control and Prevention from more than two dozen state health departments, which tallied lower rates of COVID-19 breakthrough cases for recipients of Johnson & Johnson's vaccine compared to the mRNA shots through January.
But recently published figures from the same CDC database now suggest that COVID-19 deaths among Johnson & Johnson recipients may have peaked at more than double the rate of other vaccinated Americans during the Omicron variant wave.
For the week of January 8, COVID-associated deaths among Americans who were vaccinated with Johnson & Johnson reached a rate of more than 5 out of every 100,000, according to the CDC's figures.
That's higher than the rate among recipients of the Pfizer or Moderna vaccines, which was around 2 deaths per 100,000 people.
It remains a fraction of the rate of COVID-19 deaths for unvaccinated Americans, which was close to 20 per 100,000.
Among only boosted Americans, those who had been vaccinated initially with the Johnson & Johnson shot had higher rates of COVID deaths than those who started with doses of Pfizer or Moderna.
Rates of COVID-19 breakthrough cases in the data, which CDC officials have often cited as part of their efforts to track "in real time" the effectiveness of the COVID-19 vaccines in Americans, were still similar or lower for Johnson & Johnson recipients compared to the others.
"The CDC data adds to the growing body of evidence indicating the Johnson & Johnson COVID-19 vaccine provides durable protection against breakthrough infection and hospitalization," Jake Sargent, a spokesperson for Johnson & Johnson, said in a statement.
The data is not adjusted for a range of factors that can muddy direct comparisons, like differences in underlying medical conditions or the length of time since vaccination. It also only includes data through the end of January. The average pace of new COVID-19 deaths from the Omicron wave only recently dipped below 1,000 per day nationwide.
Asked about the rates of COVID-19 deaths among Johnson & Johnson recipients, a CDC spokesperson pointed to the agency's other cohort studies into breakthrough infections. However, the CDC's most recent Omicron wave studies have so far only directly analyzed the mRNA vaccines.
"mRNA vaccines continued to be highly effective at protecting against COVID-19-associated ventilation or death, including during the Omicron period," the agency said in a statement Friday, which made no mention of Johnson & Johnson's vaccine.
A different immune response
Emerging research around the nuances of the immune response generated by the different vaccines offer clues to the differences seen between how the shots perform in the real world.
"The J&J vaccine is different in that, initially the antibody responses are quite a bit lower than the mRNA vaccines. But those responses actually are maintained very well over time, even increase a little bit," said Dr. Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center.
Johnson & Johnson publicized research last year from Barouch's team suggesting people who received its booster shots saw better antibody levels after four weeks compared to those who got only the Pfizer and BioNTech shots. That study also found Johnson & Johnson shot generated bigger increases in T cells, a different part of the immune response that kicks in after an infection.
"The T cell responses appear to be less dependent on the variants. So variants really escape antibodies, and really don't escape the CD8 T cells. So that T cell response probably has a particularly important role in protecting against severe disease, particularly with variants that largely escape antibodies," said Barouch.
Measuring and comparing the immune responses triggered by the different vaccines is a lengthy and resource-intensive process, requiring scientists to gather and carefully preserve living cells from hundreds of large blood samples. Many studies only analyze the body's first line of defense against infections — neutralizing antibodies — or only the broad immune responses in recipients of a single or handful of vaccines.
"The only way to really compare immune responses to different vaccines is to really do them all in the same lab, at the same lab truly head-to-head. We can't compare a Pfizer clinical trial paper with the Moderna clinical trial paper with the J&J clinical trial paper," said Shane Crotty, a professor at the La Jolla Institute for Immunology.
Backed by the National Institutes of Health, Crotty's team recently completed a monthslong preprint study — which has yet to be peer-reviewed — offering a first-of-its-kind accounting of the immune responses triggered by the initial shots from Johnson & Johnson, Moderna, Pfizer-BioNTech, and Novavax after six months.
The Johnson & Johnson vaccine was "not the strongest immunogen by any measurement," concluded the study's authors, though "responses were relatively stable" for all the shots.
A second booster shot?
In December, health authorities in South Africa greenlighted a request from Johnson & Johnson to add a second booster shot. In France, Johnson & Johnson recipients can top up their primary regimen with an mRNA vaccine before later getting a booster.
For now, only immunocompromised recipients of Johnson & Johnson's vaccine in the U.S. are currently eligible to receive a third dose.
But that could change soon. Both Moderna as well as Pfizer and BioNTech have announced requests to roll out additional booster shots that would include recipients of the Johnson & Johnson vaccine. The Food and Drug Administration plans to convene its outside vaccine advisers next month to discuss additional boosters.
"Given the parallel protection that we have seen with J&J that is boosted or the mRNAs that are boosted, as well as the mix and match, which have been done, where you can vaccinate with one platform and boost with the other, we have found very interestingly that it works quite well," Dr. Anthony Fauci, the president's chief medical adviser, told reporters in January when asked about the possibility the American regimen might also be changed for Johnson & Johnson.
A study backed by Fauci's agency's, the National Institute of Allergy and Infectious Diseases, published earlier this year, concluded that so-called mix-and-match boosting with the Johnson & Johnson vaccine appeared to outperform some parts of the immune response compared to those who only received the mRNA shots.
However, people who only received Johnson & Johnson's vaccine for their primary and booster shot were the only group not to reach antibody levels "correlated with 90.7% vaccine efficacy at preventing symptomatic Covid-19 in a previous study."
"In that regard, we feel that the situation that we're seeing with the mRNAs is really quite parallel with the boosted J&J — not the first dose, but the boosted J&J," Fauci had said. He declined to be interviewed for this article.