Q: What do we know about waning immunity?
A: Waning immunity refers to an individual’s initial immune-mediated protection (e.g., humoral or cell-mediated immunity) elicited by a vaccine decreasing over time. There is now extensive evidence that COVID-19 vaccine-induced antibody titers decline over time. Some evidence indicates that the T-cell response to COVID-19 may remain durable over a longer period of time, although others have found waning of SARS-CoV-2 T-memory-cell populations with a half-life of 3-5 months. Additionally, T-cell responses may be challenging to disentangle from neutralizing antibody responses, as neutralizing antibody responses rely on T-cell activation. As a result, these findings may have varying implications for the duration of clinical protection against symptomatic SARS-CoV-2 infection and severe COVID-19.
Evidence for whether waning immunity results in “waning protection” is almost always indirect because there are many immune system factors and many external, immune system-independent factors that can influence immunological protection and vaccine effectiveness over time. In fact, observations of waning protection, which may be suggested by lower population-level vaccine effectiveness estimates over time or rates of breakthrough infection, need not be solely attributable to waning immune responses.
Other factors that can contribute to time-dependent estimates of vaccine effectiveness include:
- Changes in masking and distancing behavior, public health policies and/or local disease epidemiology that influence the “force of infection” (likelihood of being exposed/infected and burden of virus with each exposure) over time. This means that vaccine efficacy estimates determined in clinical trials are context-dependent, and caution is warranted when extrapolating to new settings and circumstances.
- Changing pathogens (such as novel variants) that are capable of escaping detection by immune system responses, resulting in diminished protection conferred by vaccine-induced immune responses. Vaccine-induced immunity may be preserved but may be less effective against a new SARS-CoV-2 variant.
- Differences in the comparison groups used to estimate vaccine effectiveness. For example, the unvaccinated population may experience fewer cases because that group has a higher level of immunity due to an accumulation of infections not captured by testing. Alternatively, individuals who were vaccinated earlier in the pandemic may differ from individuals vaccinated more recently in their likelihood to have a poor initial response to the vaccine or to be exposed to SARS-CoV-2. This is the case for high-risk individuals such as older adults living in congregate living facilities as well as health care workers who were prioritized to receive COVID-19 vaccines early on during the pandemic. These populations had substantially different risk levels for severe outcomes after COVID-19 compared to the general population.
These issues are relevant because the relative contribution of these factors informs the optimal use of additional vaccine doses or “boosters” at a population level.