Immunity to SARS-CoV-2 induced by infection or vaccination

Abstract

Adaptive immune responses play critical roles in viral clearance and protection against re-infection, and SARS-CoV-2 is no exception. What is exceptional is the rapid characterization of the immune response to the virus performed by researchers during the first 20 months of the pandemic. This has given us a more detailed understanding of SARS-CoV-2 compared to many viruses that have been with us for a long time. Furthermore, effective COVID-19 vaccines were developed in record time, and their rollout worldwide is already making a significant difference, although major challenges remain in terms of equal access. The pandemic has engaged scientists and the public alike, and terms such as seroprevalence, neutralizing antibodies, antibody escape and vaccine certificates have become familiar to a broad community. Here, we review key findings concerning B cell and antibody (Ab) responses to SARS-CoV-2, focusing on non-severe cases and anti-spike (S) Ab responses in particular, the latter being central to protective immunity induced by infection or vaccination. The emergence of viral variants that have acquired mutations in S acutely highlights the need for continued characterization of both emerging variants and Ab responses against these during the evolving pathogen-immune system arms race.

Keywords: B cells; COVID-19; SARS-CoV-2; antibody responses; population immunity; vaccines.

Fig. 1

(a) Kinetics of innate and adaptive immune responses following SARS‐CoV‐2 infection. Following rapid action by the innate immune system immediately after virus exposure, B and T cell responses develop within the first weeks. Short‐lived IgM antibodies are produced by responding B cells initially and is followed by a more persistent and high‐affinity class‐switched response. (b) Production of highly diverse virus‐specific antibodies. After cognate antigen encounter, activated naïve B cells enter the germinal center (GC) where they receive T cell help to generate a high‐affinity antibody repertoire. Short‐lived peripheral plasma cells produce most antibodies during the infection, while GC‐derived memory B cells and bone marrow‐resident plasma cells cooperate to provide long‐lasting protection against re‐infection. (c) Maturation of the antibody response following viral clearance. While the magnitude of the antibody response gradually wanes after the virus replication is controlled, the quality of the B cell response continues to improve for several months following the infection

Fig. 2

Vaccine platforms in use or under clinical evaluation to prevent COVID‐19. Currently, several inactivated whole virus vaccines as well as SARS‐CoV‐2 spike‐encoding vaccines based on mRNA or adenovirus technology are approved for clinical use. Furthermore, spike protein subunit vaccines have shown high efficacy in phase 3 clinical trials and should be approved for use shortly

Fig. 3

Schematic of the SARS‐COV‐2 spike glycoprotein and location of mutations in VoCs. Left: Schematic of the spike trimer highlighting key domains including the RBD, NTD and S2. Right (side and top view): ChimeraX was used to illustrate selected residues in the spike trimer that are mutated in selected VOCs known at the time of writing. Mutations can be common or unique to different VOCs