Plus, antibodies aren’t the body’s only defense to create immunity – we also manufacture T cells, memory B cells and others. Clinical trials of the vaccine have not attempted to measure the number of cells required to create an effective defense against the virus. They reported only clinical assessment criteria, for example whether a person has become seriously ill or has died as a result of the illness. So focusing only on antibodies can miss important parts of the immune response.
“I try not to use words like ‘you didn’t respond’ to the vaccine when someone isn’t making antibodies,” says Haidar, a senior researcher on a larger study which recruits people with a range of immune deficiencies, including HIV, to study the vaccine response of Covid. “I’m afraid it could lead to hesitation in getting vaccinated if the message is that the vaccine isn’t working for you. I think we need to be a little more nuanced to take into account the complexities that other parts of the immune system might have been enhanced by vaccines. “
Even in the few studies done so far, it is clear that the immune response to vaccines varies depending on the age of the patient, the type of immune deficiency they are experiencing, the type of transplant they have received, the specific medications he’s taking, the time since the transplant or the last dose, and a host of other factors. The likelihood of abundant antibody production appears to be higher, for example, in patients taking immunosuppressive drugs to treat chronic inflammatory diseases than in transplant and cancer patients. Studies by Segev and his team show better levels of antibody production in these patients after a and of them dose. But a separate prepublication, produced by Washington University School of Medicine in St. Louis and UC San Francisco, shows a wide range of responses depending on the drug regimen taken by the patient.
This may provide a clue for managing the vulnerability of patients, so that they can move closer to the type of immune protection healthy people receive from Covid vaccines. “One thing we tell patients on withdrawal, who have not yet been vaccinated, is to consider saving their medications,” says Alfred HJ Kim, lead author of this study and assistant professor of rheumatology and immunology at the University of Washington. “Obviously, if you have drugs, you risk flare-ups. And if you’re going to explode, it could make the side effects of your vaccine worse, or it could make the vaccine itself less effective. It is a really delicate situation.
And, legally, doctors currently cannot advise patients to request additional doses of the Covid vaccine. The FDA has only cleared one or two doses for all the vaccines it has let into the US market. For the Segev team’s study, the doctors did not order a third dose – the patients found the third doses on their own, in a way the study did not specify. The Hopkins team followed the results.
Still, there is evidence in the medical literature to support the usefulness of additional doses. For example, the French government recommended a third dose for anyone who is immunocompromised. And in the United States, it has been understood for years that a second dose seasonal flu vaccine and larger doses hepatitis B vaccine is needed to create immunity in them.
But more data will have to be gathered to be sure. The Hopkins team is considering a larger trial in which immunocompromised patients seeking a third dose are formally enrolled and followed. And despite the appeal of higher protection, they don’t urge immunocompromised patients to start freelance for their third injection. “There are risks in taking third doses,” says Segev. “There is a risk that the third dose will activate your immune system and cause either overt rejection or some sort of subclinical thing, where you start to develop a few more antibodies against your transplanted organ. It is important that people who receive third doses are part of the research protocols or do so in collaboration with their physicians who have assessed the risks and benefits.
If trials like this can provide any data—another, recently announced, is being conducted by the National Institutes of Health – they could do more than just let the immunocompromised come back to life. They may also shed light on aspects of the immune system and its interaction with vaccines that are still poorly understood. And that will be beneficial not only during this pandemic, but for everything we need to protect ourselves next time.
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