Review
doi: 10.1038/s41577-021-00550-x.
Epub 2021 Apr 29.
Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection
Deborah Cromer #
1
, Jennifer A Juno #
2
, David Khoury
1
, Arnold Reynaldi
1
, Adam K Wheatley
2
, Stephen J Kent #
3
, Miles P Davenport #
4
Affiliations
- PMID: 33927374
- PMCID: PMC8082486
- DOI: 10.1038/s41577-021-00550-x
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Review
Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection
Deborah Cromer et al.
Nat Rev Immunol.
2021 Jun.
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Abstract
Immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is central to long-term control of the current pandemic. Despite our rapidly advancing knowledge of immune memory to SARS-CoV-2, understanding how these responses translate into protection against reinfection at both the individual and population levels remains a major challenge. An ideal outcome following infection or after vaccination would be a highly protective and durable immunity that allows for the establishment of high levels of population immunity. However, current studies suggest a decay of neutralizing antibody responses in convalescent patients, and documented cases of SARS-CoV-2 reinfection are increasing. Understanding the dynamics of memory responses to SARS-CoV-2 and the mechanisms of immune control are crucial for the rational design and deployment of vaccines and for understanding the possible future trajectories of the pandemic. Here, we summarize our current understanding of immune responses to and immune control of SARS-CoV-2 and the implications for prevention of reinfection.
Conflict of interest statement
The authors declare no competing interests.
Figures
a | Dynamics of immune decay following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The rates of loss of SARS-CoV-2 neutralizing antibodies and binding antibodies (IgG and IgA) as well as of CD4+ T cells, CD8+ T cells and memory B cells are shown as documented by several independent studies (includes preprint data, not yet peer reviewed),,,,–,,,–. Neutralizing antibody responses show a biphasic decay over the first months after infection. The rapid decay observed in the neutralization titre in the first 1–2 months after infection is consistent with the decay kinetics of IgA responses and IgM responses (not shown). The slower decay of neutralization titre after 2 months is more consistent with the slow decay of IgG responses. T cell responses decay at a slightly slower rate than IgG over the first few months after infection, whereas memory B cell responses increase. The plotted data are derived from the half-lives reported directly by the authors of each study or from our calculation of half-lives based on raw data extracted from the original publication. Details of the original studies, data extraction and analysis are provided in Supplementary Table 1. Direct comparisons of the absolute magnitude of responses between studies are not possible owing to the different assays used. However, the rate of decay for each study as a percentage of the maximum uses a consistent measure over time. b | Comparison of the kinetics of antibody decay following infection with SARS-CoV, or human coronavirus (hCoV) and following mild-to-moderate SARS-CoV-2 infection. A high variability is seen between studies; however, a rapid early decay followed by a slowing decay is seen for most serological responses. c | Comparing the durability of vaccine-induced, and natural immunity to SARS-CoV-2. There is no evidence that vaccine-induced responses are more durable than convalescent responses (preprint data, not yet peer reviewed).
Immune memory could function to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at several stages. Residual levels of neutralizing antibodies may block the entry of virus into host cells or prevent the early dissemination of virus. Even if viral growth is established, residual antibody and cellular responses may function to slow viral growth, providing a longer window of time for the action of recall immune responses. Recall responses start to take effect later in infection, boosting immune-mediated control and reducing the virus to low levels. Depending on the timing and efficacy of immune control, infection may vary from undetectable or mild, through to severe infection with viral detection and immune boosting.
Immune responses, particularly neutralizing antibody responses, to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been observed to decay rapidly in the first few months after infection but the rate of decay seems to slow with time. a | In an ideal scenario, immunity remains above a protective threshold for a prolonged period, providing strong immunity from reinfection. b | Immunity may drop below the threshold required to prevent infection but still provide sufficient protection against severe illness. If viral levels after reinfection are high enough to enable transmission, the endemic spread of infection may boost memory responses to maintain immunity at protective levels. c | Weak immune memory, rapidly decaying immunity or viral antigenic variation may result in the level of immune memory dropping below the threshold required to protect against severe disease, thereby exposing the patient to a similar risk to that seen in primary infection.
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