Recent studies seem to paint a grim picture of how long COVID-19 immunity lasts, finding evidence of viral antibody counts plummeting in COVID-19 patients a mere two months after an initial infection. Some have worried that these people are vulnerable to reinfection and that long-lasting vaccines could be more difficult to develop, making widespread herd immunity impossible to obtain.
But experts are not terribly concerned about these antibody findings — balking at the suggestion that this initial data points to risk of reinfection, and pushing back against claims that waning antibody immunity may end hopes of a long-lasting vaccine. For starters, our immune system has other ways of fighting infections besides antibodies. And even if our natural immune response is sub-par, a vaccine would be designed to produce a better immune response than natural infection.
"The whole point of a well-developed vaccine is to sidestep these limitations [of natural infection] and optimize the vaccine in a way that ensures a robust, long-lasting immune response," said Daniel Altmann, an immunologist at the Imperial College London.
That is not to say the recent research on decreasing antibody levels in COVID-19 patients is not robust. The general principle of tracking viral antibody levels to estimate immunity to a specific disease is well-established. Antibodies recognize the shape of some part of a virus and stick to it, either identifying it for later destruction or neutralizing the pathogen on the spot. As long as a patient maintains a healthy number of antibodies for a given virus in his or her bloodstream, the body remains alert and ready to fight off future infection. Vaccines broadly operate on the same principle, stimulating the immune system to produce antibodies preemptively.
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"Scientists have been studying different antibodies for decades, and the methods to analyze them are standardized," said Lisa Butterfield, an immunologist at the University of California San Francisco and the Parker Institute for Cancer Immunotherapy. "Once tests specific to COVID-19 were developed, it was relatively straightforward to follow the levels of antibodies over time."
Following these antibody levels in COVID-19 patients has produced sobering results — at least at first glance. One preliminary study posted on the preprint server medRxiv in mid-July by researchers at King's College London found that individuals with mild infections had almost none of their hard-earned COVID-19 antibodies 60 days after infection. (That study has not yet been published in a peer-reviewed journal.) And a recent letter submitted to The New England Journal of Medicine similarly found that antibody levels decreased exponentially within 90 days of infection.
But these decreases in antibody counts may not be cause for concern, from a clinical perspective. "The conclusions may be a bit overstated," said Steven Varga, an immunologist at the University of Iowa. "We always want long-term, durable immune responses, but it is normal with many vaccines and pathogens to have a decrease in antibody titers [levels] over time. I don't think that the drop that these publications are showing is something to be terribly alarmed about."
Besides, how many antibodies are enough to prevent reinfection? "We do not yet know," Butterfield said. "Low levels of good, neutralizing antibodies could be enough."
Beyond antibodies
Antibody counts are also only a small part of the complex story of human immunity. The immune system's white blood cells are broadly split into two categories: B cells, which manufacture antibodies, and T cells that bind to and kill infected cells. Both of these cells can live in the body for decades, and ramp up in response to a disease that the body has already encountered.
Waning antibody levels may mean that B cell immunity falls off after a few weeks, but this does not necessarily mean that T cell levels fall at comparable rates. Indeed, a recent study in the journal Nature found that 23 patients who recovered from SARS, a close cousin of COVID-19, still possessed SARS-reactive T cells more than 15 years after the SARS outbreak (which ended in 2003.) And a preprint study posted to medRxiv in June suggested that some patients with no detectable antibodies still maintained T cell immunity to the virus that causes COVID-19.
"The only catch," Altmann cautioned, "is that we've never seen a formal proof that T cells are functional alone [without antibodies]. In the heat of battle, would T cells be sufficient to save you?" This is an important question because a robust immune response usually involves T cells and B cells cross-checking with one another. But Altmann suspects that T cells are capable of preventing an infection without input from B cells. "I have seen examples of patients with B cell deficiencies who recovered from COVID-19 just fine," he said. "But the jury isn't back yet on proving that T cells alone are protective."
Still hope for a vaccine
Regardless of what these waning antibody levels mean for overall immunity, what the data certainly do not represent is a significant setback for any of the candidate COVID-19 vaccines. Even if we end up with a vaccine that produces antibodies that drop off after a few months, and even if the antibody counts are actually low enough to render patients vulnerable to infection, and even if T cells prove insufficient to fight off the disease alone — an unlikely scenario — a short-term vaccine still might be enough to stop the pandemic in its tracks.
"We do not necessarily need twenty years of immunity to have an effective vaccine," Varga said. "We need something that will give us immunity for the short-term, long enough that we can break this transmission cycle."
Even more promising, the most advanced candidate vaccines do not make use of dead or attenuated coronavirus, which run the risk of producing disappointing immune responses similar to those observed in natural infections, Altmann said. Instead, frontrunners such as the Oxford or Moderna vaccines employ relatively new technologies. The Oxford vaccine uses a genetically engineered version of a common cold virus (called an adenoviral vector) to carry genetic material from the new coronavirus; and the Moderna vaccine uses messenger RNA (mRNA) to instruct cells to make a very small part of the new coronavirus.
Both of these methods may produce more long-lasting immune responses than traditional vaccines made of whole virus, because they can be quickly modified and tested in cells to produce a strong and lasting immune response. "Because you have engineered this platform, you can optimize its immune response," Altmann said.
No adenoviral or mRNA vaccines are currently approved for human use, but "I would be amazed if waning antibody levels were an issue" with these vaccines, Altmann said.
Originally published on Live Science.
