When it came to the coronavirus vaccination, the stimulus was the third time for Esther Jones, a dialysis nurse in rural Oregon. After two doses of the Pfizer BioNTech vaccine failed her immune system to produce antibodies, she sought out a third, this time the Moderna shot.
It worked. Blood tests showed a reasonable antibody response, but it was less than that in healthy people. She received a fourth dose last month in hopes of getting the levels even higher.
Ms. Jones, 45, had a kidney transplant in 2010. Since then, she has been taking drugs that suppress the immune response to prevent rejection of the organ. She believed she would have difficulty responding to a coronavirus vaccine and enrolled in one of the few studies to test the benefits of a third dose in people with weak immune systems.
Since April, healthcare providers in France have been routinely giving a third dose of a two-dose vaccine to people with certain immune disorders. The number of organ transplant recipients who had antibodies rose from 40 percent after the second dose to 68 percent four weeks after the third dose, a team of French researchers recently reported.
The study that Ms. Jones participated in showed similar results in 30 organ transplant recipients who procured the third dose for themselves.
Being susceptible to infection even after vaccination is “very scary and frustrating,” said Dr. Dorry Segev, a transplant surgeon at Johns Hopkins University who led the study. “They must keep acting unvaccinated until we find a way to give them better immunity.”
In the United States, however, there is no concerted effort by federal agencies or vaccine manufacturers to test this approach, so people with low immunity have more questions than answers. The Centers for Disease Control and Prevention, the Food and Drug Administration, and the National Institutes of Health even advise against testing to find out who is protected. And academic scientists are hindered by the rules that restrict access to the vaccines.
“There should already be a nationwide study examining post-transplant patients who are given booster shots,” said Dr. Balazs Halmos, an oncologist at Montefiore Medical Center in the Bronx, who led a study that showed that some cancer patients were not responding to the vaccinations. “It shouldn’t be our little team here in the Bronx trying to figure that out.”
An estimated 5 percent of the population is considered to be immunocompromised. The list of causes is long: some cancers, organ transplants, chronic liver disease, kidney failure and dialysis, and drugs like rituxan, steroids and methotrexate, which are used by around 5 million people for conditions like rheumatoid arthritis and psoriasis to some forms of cancer.
“These are the people who are left behind,” said Dr. Jose U. Scher, a rheumatologist at NYU Langone Health who led a study on the effect of methotrexate on the vaccines.
Not everyone who has any of these risk factors is affected. But without further research, it’s impossible to know who and how many additional doses of the vaccines might need. In addition to the risk of Covid-19, there is also evidence that low immunity can allow the virus to multiply in the body for long periods of time, potentially leading to new variants.
An infusion of monoclonal antibodies can help some people who don’t make antibodies themselves – but again, the idea is not well explored, said John Moore, a virologist at Weill Cornell Medicine in New York.
The use of monoclonal antibodies “makes a lot of sense for this group of people, so I would like companies to become more active in this area,” he said. “Government support or pressure would also help.”
July 4, 2021, 4:20 p.m. ET
The third dose approach has widespread support among researchers as it has clear precedents. Immunocompromised people receive booster vaccinations against, for example, hepatitis B and influenza. And stopping methotrexate after a flu shot is known to improve the effectiveness of the vaccine – evidence that led the American College of Rheumatology to recommend pausing methotrexate use for a week before immunizing it against the coronavirus .
Several studies have shown that a third dose of coronavirus vaccine could be successful in patients who had no detectable antibodies after the first or second dose. But research lagged behind.
Moderna is preparing to test a third dose in 120 organ transplant recipients, and Pfizer – which makes some immunosuppressive drugs – plans to study 180 adults and 180 children with an immune disorder.
The companies turned down at least two independent teams hoping to study the effects of a third dose.
The NIH is recruiting 400 immunocompromised people for a study that will track their antibody and immune cells for up to 24 months – but there are no studies looking at a third dose.
“Unfortunately, it takes time, especially as a government agency,” said Emily Ricotta, an epidemiologist at the National Institute for Allergies and Infectious Diseases. “We have to go through a lot of regulatory and approval processes to carry out such projects.”
But this explanation does not satisfy some researchers. Many medical centers already have unresponsive patient populations so federal agencies could easily organize a clinical trial, noted Dr. Shear. “It’s a very simple study,” he said. “There’s no rocket science here.”
Previous studies indicated that many cancer patients did not respond to the vaccines, but these analyzes were done after the patients received a single dose. A new study released this month by Dr. Halmos, published by Montefiore Medical Center and colleagues, has addressed some of those fears. According to the great analysis, the vaccines appear to work well in patients with a variety of solid and liquid tumors.
But 15 percent of those who had blood cancer and 30 percent of those who were taking drugs that suppress the immune system had no detectable antibodies after the second dose. Dr. Halmos said he and his colleagues would like to test whether a third dose could benefit these people but have not yet been given access to the vaccines.
Dr. Segev found in a previous study that less than half of 658 organ transplant recipients had measurable antibodies after both doses of a Pfizer-BioNTech or Moderna mRNA vaccine. But to investigate the result, they had to recruit volunteers like Ms. Jones, who had received the third dose herself.
The scientists found that a third dose increased antibody levels in all 30 organ transplant recipients with low or undetectable antibody levels.
Ms. Jones said many people like her have felt abandoned by the federal government – especially given the risk of more contagious varieties floating around in the United States.
Some members of a Facebook group for immunocompromised people desperate for protection have been given a third dose of mass vaccination sites where vendors haven’t checked records or even crossed state lines, she said. Even so, most of them continue to wear masks to protect themselves – and as a result have had to endure harassment at times.
“It makes me really sad that so many people in this world have done masking, this super-political thing that should never have been,” she said. “That makes it harder for us to take care of ourselves.”