Immunological memory to SARS-CoV-2 infection and COVID-19 vaccines

Abstract

Immunological memory is the basis of protective immunity provided by vaccines and previous infections. Immunological memory can develop from multiple branches of the adaptive immune system, including CD4 T cells, CD8 T cells, B cells, and long-lasting antibody responses. Extraordinary progress has been made in understanding memory to SARS-CoV-2 infection and COVID-19 vaccines, addressing development; quantitative and qualitative features of different cellular and anatomical compartments; and durability of each cellular component and antibodies. Given the sophistication of the measurements; the size of the human studies; the use of longitudinal samples and cross-sectional studies; and head-to-head comparisons between infection and vaccines or between multiple vaccines, the understanding of immune memory for 1 year to SARS-CoV-2 infection and vaccines already supersedes that of any other acute infectious disease. This knowledge may help inform public policies regarding COVID-19 and COVID-19 vaccines, as well as the scientific development of future vaccines against SARS-CoV-2 and other diseases.

Keywords: adenoviral vectors; coronavirus; hybrid immunity; mRNA vaccines; memory B cells; memory T cells; natural immunity; protein vaccine.

Figure 1

Components of immune memory. Virus‐specific CD4 T cells, CD8 T cells, Abs, and B_Mem cells constitute the four major components of immune memory to a viral infection

Figure 2

Kinetics of immune memory to SARS‐CoV‐2 infection and COVID‐19 vaccines. Schematics of immune memory components against SARS‐CoV‐2. (A) Memory CD8 T cells, (B) memory CD4 T cells, (C) memory T_FH cells, (D) neutralizing antibodies, and (E) B_Mem cells. For T cell memory, with vaccines memory is to spike, and with infection, memory is to the entire virus. For B cell memory, spike‐specific is shown in all cases. "Inf" = SARS‐CoV‐2 infected. "Hybrid" = Hybrid immunity, infected and then vaccinated. "mRNA" = Moderna mRNA‐1273 or Pfizer/BioNTech BNT162b2, a 3 dose regimen. "NVX" = Novavax NVX‐CoV2373, given as the 2‐dose regimen in the main clinical trials. "J&J" = Janssen Ad26.COV2.S, given as the 1‐dose approved by EUAs. Lines are color coded by vaccine. CD8 T cell % indicates the % of individuals with detectable CD8 T cell memory at 3–6 months. Scales are non‐quantitative, but the antibody scale approximates log10 and the cellular scales approximate log2. For hybrid immunity, in this schematic, the vaccination occurs at approximately 6 months, indicated by the blue triangle. For mRNA vaccines, in this schematic, the 1st two dose are given at d1 and d21‐28, with the 3rd dose ("booster") given at approximately 8 months, indicated by the red arrows

Figure 3

Components of local tissue immunity. Human immune responses are most often measured in blood, but immune responses at local sites of infection and/or portals of entry are important and may not be directly reflected by blood measurements