Should people with immune problems receive a third dose of the vaccine?


As for the coronavirus vaccination, the third time has been the charm of Esther Jones, a dialysis nurse in the Oregon countryside. After two doses of the Pfizer-BioNTech vaccine failed to get her immune system to produce antibodies, she sought a third, this time the Moderna vaccine.

It worked. Blood tests revealed a reasonable antibody response, although less than what would be detected in healthy people. She received a fourth dose last month in hopes of raising the levels even more.

Jones, 45, had a kidney transplant in 2010. To prevent organ rejection, she has been taking drugs that suppress the immune response. She expected to have trouble responding to a coronavirus vaccine and enrolled in one of the few studies to date to test the usefulness of a third dose in people with weakened immune systems .

Since April, healthcare providers in France have routinely administered a third dose of a two-dose vaccine to people with certain immune diseases. The number of organ transplant recipients who presented with antibodies rose to 68% four weeks after the third dose, from 40% after the second dose, a team of French researchers recently reported.

The study Jones enrolled in showed similar results in 30 organ transplant recipients who self-procured the third dose.

Being vulnerable to infection even after inoculation is “very frightening and frustrating” for immunocompromised people, said Dr. Dorry Segev, a transplant surgeon at Johns Hopkins University who led the study. “They have to continue to act without being vaccinated until we find a way to give them better immunity.”

But in the United States, there is no concerted effort by federal agencies or vaccine makers to test this approach, leaving people with low immunity with more questions than answers. The Centers for Disease Control and Prevention, the Food and Drug Administration, and the National Institutes of Health even recommend against testing to find out who is protected. And university scientists are blocked by rules that limit access to vaccines.

“There should already be a national study of post-transplant patients receiving booster shots,” said Dr. Balazs Halmos, oncologist at Montefiore Medical Center in the Bronx, who conducted a study showing that some cancer patients did not respond to the vaccines. “It shouldn’t be our little team here in the Bronx trying to figure this out.”

It is estimated that 5% of the population is considered to be immunocompromised. The list of causes is long: certain cancers, organ transplants, chronic liver disease, kidney failure and dialysis, and drugs like Rituxan, steroids and methotrexate, which are taken by around 5 million people for the conditions. ranging from rheumatoid arthritis and psoriasis to certain cancers.

“These are the people who are being left behind,” said Dr. Jose U. Scher, rheumatologist at NYU Langone Health who led a study on the effect of methotrexate on vaccines.

Not all people with any of these risk factors are affected. But without more research, it’s impossible to know who might need additional doses of the vaccine and how much. Besides the risk of COVID-19, there is also some evidence that low immunity can allow the virus to continue to replicate in the body for long periods of time, potentially leading to new variants.

An infusion of monoclonal antibodies may help some people who don’t produce antibodies on their own – but again, the idea isn’t fully explored, said John Moore, a virologist at Weill Cornell Medicine in New York. York.

The use of monoclonal antibodies “makes a lot of sense for this group of people, so I would like companies to be more active in this area,” he said. “Government support or pressure would also help. ”

The third dose approach enjoys wide support among researchers because there is a clear precedent. People who are immunocompromised receive booster doses of hepatitis B and influenza vaccines, for example. And stopping methotrexate after receiving a flu shot is known to improve the potency of the vaccine – evidence that led the American College of Rheumatology to recommend stopping use of methotrexate for a week before being immune to the coronavirus.

Several studies have indicated that a third dose of the coronavirus vaccine may be successful in patients who did not have detectable antibodies after the first or second dose. But the research is behind schedule.

Moderna is preparing to test a third dose in 120 organ transplant recipients, and

– which produces immunosuppressive drugs – plans a study on 180 adults and 180 children with immune disease.

The companies have turned down at least two independent teams that hoped to study the effects of a third dose.

The NIH is recruiting 400 immunocompromised people for a trial that would track their levels of antibodies and immune cells for up to 24 months – but does not have a third dose trial.

“It takes time, unfortunately, especially as a government agency,” said Emily Ricotta, epidemiologist at the National Institute of Allergy and Infectious Diseases. “We have to go through a lot of regulatory and approval processes to do these kinds of projects. ”

But this explanation does not satisfy some researchers. Many medical centers already have groups of patients who have not responded to vaccines, so federal agencies could set up a clinical trial without too much difficulty, Scher noted. “It’s a very simple study,” he says. “There is no rocket science here.”

Previous studies suggested that many people with cancer would not respond to vaccines, but these tests were done after patients received a single dose. A new study released this month by Halmos and his colleagues allayed some of those fears. The vaccines appear to work well in patients with a wide range of solid and liquid tumors, according to the big analysis.

But 15% of those with blood cancers and 30% of those taking drugs that suppress the immune system had no detectable antibodies after the second dose. Halmos said he and his colleagues were eager to test whether a third dose could benefit these people, but have not yet been able to access the vaccines.

Segev’s team found in an earlier study that less than half of 658 organ transplant recipients had measurable antibodies after two doses of an mRNA vaccine made by Pfizer-BioNTech or Moderna. But to follow through on the discovery, they had to resort to recruiting volunteers like Jones who had obtained third doses on their own.

Scientists found that a third dose increased antibody levels in 30 organ transplant recipients who had low or undetectable antibody levels.

Jones said many people like her feel abandoned by the federal government – especially with the threat of more contagious variants circulating in the United States.

Some members of a Facebook group for desperate immunosuppressed people received a third dose at mass vaccination sites where providers do not check records, or even cross state borders, she said. . Even so, most continue to wear masks for protection – and have sometimes faced harassment as a result.

“It really saddens me that so many people in this world have been doing masking, this super political thing when it never should have been,” she said. “It makes it harder for us to take care of ourselves. ”


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