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| From Paul Offit On February 28, 2024, the CDC issued a press release stating that people 65 years of age or older should now receive an additional dose of the 2023-2024 COVID vaccine. To understand this recommendation, let’s go back to when the CDC first recommended booster doses and why. In December 2020, the Pfizer and Moderna vaccines were administered as a series of two doses separated by 3 or 4 weeks. By the end of 2021, these two-dose vaccines were doing what they were intended to do—keep people out of the hospital, out of the intensive care unit and out of the morgue. Then, in December 2021, the omicron variant, which was immune-evasive, entered the United States. In response, the CDC performed a series of studies showing that a third dose and, to a lesser extent, a fourth dose prevented hospitalizations better than two doses. Not everyone, however, benefited equally. Those who benefited from these booster doses fell into four high-risk groups: 1) those over 75 years of age, 2) those who had medical conditions such as chronic lung, heart, kidney or liver disease, 3) those who were receiving medicines that suppressed the immune system, and 4) those who were pregnant. Why, now, does the CDC recommend two booster doses during the same year for those over 65? To make sense of this recommendation, we need to understand some basic tenets of the immune system; specifically, which aspects of the immune system protect against mild disease and which against severe disease. They aren’t the same. The key determinant for protection against mild illness is the presence of virus-specific antibodies present in the bloodstream at the time of exposure to the virus. The good news is that these antibodies are readily induced by natural infection or vaccination. The bad news is that they don’t last very long—usually 3 to 6 months—before they fade away. Therefore, for diseases like COVID, protection against mild illness afforded by vaccination is always short-lived. Always. Protection against severe illness, on the other hand, isn’t dependent on antibodies present at the time of exposure; it’s dependent on immunological memory cells, like memory B cells, which can be activated to make antibodies, or memory T cells, which can be activated to kill virus-infected cells. The good news about memory cells is that they are long-lived, often for decades. The bad news is that it takes time after exposure to the virus for these memory cells to become activated. For diseases like COVID, which has a short incubation period, memory cells will protect against severe disease but not mild disease. If the goal of the COVID vaccine is to protect against severe disease, and protection against severe disease is mediated by immune memory cells, then the critical question is what groups lack high levels of immune memory cells. The CDC assumed that those over 65 who have been vaccinated or naturally infected might not have high levels of memory cells. So, they benefit from these extra booster doses. But is this true? It’s not hard to figure this out. The CDC, in collaboration with immunologists, should study the level and duration of immune memory cells in the months to years after vaccination to determine who is at greatest risk of severe disease. These studies should be done in 1) healthy children and adults, 2) the elderly, 3) those who are immune compromised for a variety of reasons, and 4) pregnant people. Then and only then will we know who is most likely to benefit from a single booster dose or two booster doses each year. As it stands, the recommendation for those over 65 to receive two booster doses during the year will likely help some high-risk people to avoid hospitalization with COVID. But it remains incumbent upon CDC epidemiologists combined with academic immunologists to define more clearly who among that group really benefits. We await better data. |