Covid-19 Antibodies May Fade But Vaccine Hopes Have Not

September 4, 2020

Recent studies seem to paint a bleak picture of the duration of COVID-19 immunity, finding evidence that COVID-19 patients experience a dramatic drop in viral antibody counts just two months after initial infection. Some worry that these people are vulnerable to reinfection and that a long-acting vaccine may be more difficult to develop, making widespread community immunity unavailable.

But experts aren’t very worried about these antibody findings – taking issue with the notion that this initial data points to a risk of re-infection and refuting the notion that waning antibody immunity could end hopes for a long-acting vaccine. First of all, our immune system has other ways to fight infection besides antibodies. And even if our natural immune response is subpar, vaccines are designed to produce a better immune response than natural infection.

“The whole point of a well-designed vaccine is to avoid these limitations [of natural infection] and to optimize the vaccine in a way that ensures a strong, long-lasting immune response,” says Daniel Altmann, an immunologist at Imperial College London.

That’s not to say that recent studies on lowering antibody levels in COVID-19 patients aren’t robust. The general principle of tracking viral antibody levels to estimate immunity to specific diseases is well established. Antibodies recognize the shape of certain parts of the virus and stick to it, either recognizing it for later destruction or neutralizing the pathogen in situ. As long as the patient maintains a healthy number of antibodies to a particular virus in his or her blood, the body remains alert and ready to fight off future infections. Vaccines work in much the same way, stimulating the immune system to preemptively produce antibodies.

“Scientists have been studying different antibodies for decades, and the methods for analyzing them are standardized,” says Lisa Butterfield, an immunologist at UCSF and the Parker Institute for Cancer Immunotherapy.” Once a specific test for COVID-19 is developed, it is possible to track antibody levels more directly over time.”

Tracking these antibody levels in COVID-19 patients has already produced sobering results – at least at first glance. A preliminary study by researchers at King’s College London, published in mid-July on the preprint server medRxiv, found that mildly infected individuals had virtually none of their hard-earned COVID-19 antibodies within 60 days of infection. (The 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 dropped exponentially within 90 days of infection.

From a clinical standpoint, however, these decreases in antibody numbers may not be of concern.” The conclusion may be a bit overstated,” says Steven Varga, an immunologist at the University of Iowa.” We always want a long-term, durable immune response, but for many vaccines and pathogens, it’s normal for antibody titers [levels] to drop over time. I don’t think the decline shown in these publications is something to be very alarmed about.”

Furthermore, how many antibodies are sufficient to prevent re-infection?” We don’t know yet,” says Butterfield.” Low levels of good, neutralizing antibodies may be enough.”

Beyond antibodies
Antibody counts are also only a small part of the complex story of human immunity. The white blood cells of the immune system are roughly divided into two categories.B cells, which make antibodies, and T cells, which bind to and kill infected cells. Both types of cells can survive for decades in the body and increase dramatically in response to diseases that the body is already encountering.

A drop in antibody levels may mean that B-cell immunity declines after a few weeks, but that doesn’t necessarily mean that T-cell levels will decline at a comparable rate. In fact, a recent study in Nature found that 23 patients who recovered from SARS (a close relative of COVID-19) still had SARS-responsive T cells more than 15 years after the SARS outbreak (which ended in 2003). And a preprint study published to medRxiv in June showed that some patients with no detectable antibodies still maintained T-cell immunity to the virus that causes COVID-19.

“The only problem,” Altmann cautioned, “is that we’ve never seen formal evidence that T cells work alone [without antibodies]. In the heat of battle, are T cells enough to save you?” That’s an important question because a strong immune response usually involves T and B cells cross-checking each other. But Altmann suspects that T cells can prevent infection without B-cell input.” I’ve seen examples of B-cell-deficient patients recovering from COVID-19,” he said.” But the jury isn’t back on proving that T cells alone have a protective effect.”

There is still hope for the vaccine
Whatever these diminished antibody levels mean for overall immunity, these data certainly don’t represent a major setback for any of the COVID-19 vaccine candidates. Even if the vaccine we end up with produces antibodies that fall off after a few months, even if the antibody numbers are actually low enough to make patients susceptible to infection, and even if T cells prove insufficient to fight the disease alone – an unlikely scenario – a short-term vaccine may still be enough to stop the epidemic in its tracks.

“We don’t necessarily need 20 years of immunity to have an effective vaccine,” says Varga.” What we need is something that gives us short-term immunity, long enough that we can break the cycle of transmission.”

More promising, Altmann said, is that the most advanced vaccine candidates do not utilize dead or attenuated coronaviruses, which have the potential to produce a disappointing immune response similar to that observed in natural infections. Instead, the leaders, such as the Oxford or Moderna vaccines, use relatively new technology. The Oxford vaccine uses a genetically engineered version of the common cold virus (called an adenovirus vector) to carry the genetic material of the new coronavirus, while the Moderna vaccine uses messenger RNA (mRNA) to instruct cells to make a very small fraction of the new coronavirus.

Both approaches may produce a more durable immune response than traditional vaccines made from whole viruses because they can be quickly modified and tested in cells to produce a strong and long-lasting immune response.” Because you’ve designed the platform, you can optimize it for an immune response,” says Altmann.

No adenovirus or mRNA vaccines have been approved for use in humans, but “I would be surprised if attenuated antibody levels are an issue” with these vaccines, Altmann said.