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. 2022 Dec 16;50(6):1643-1658.
doi: 10.1042/BST20220415.

Humoral immunity and B-cell memory in response to SARS-CoV-2 infection and vaccination

Holly A Fryer  1 , Gemma E Hartley  1 , Emily S J Edwards  1 , Robyn E O'Hehir  1   2 , Menno C van Zelm  1   2
Affiliations

Humoral immunity and B-cell memory in response to SARS-CoV-2 infection and vaccination

Holly A Fryer et al. Biochem Soc Trans. .

Abstract

Natural infection with SARS-CoV-2 induces a robust circulating memory B cell (Bmem) population, which remains stable in number at least 8 months post-infection despite the contraction of antibody levels after 1 month. Multiple vaccines have been developed to combat the virus. These include two new formulations, mRNA and adenoviral vector vaccines, which have varying efficacy rates, potentially related to their distinct capacities to induce humoral immune responses. The mRNA vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) elicit significantly higher serum IgG and neutralizing antibody levels than the adenoviral vector ChAdOx1 (AstraZeneca) and Ad26.COV2.S (Janssen) vaccines. However, all vaccines induce Spike- and RBD-specific Bmem, which are vital in providing long-lasting protection in the form of rapid recall responses to subsequent infections. Past and current SARS-CoV-2 variants of concern (VoC) have shown the capacity to escape antibody neutralization to varying degrees. A booster dose with an mRNA vaccine following primary vaccination restores antibody levels and improves the capacity of these antibodies and Bmem to bind viral variants, including the current VoC Omicron. Future experimental research will be essential to evaluate the durability of protection against VoC provided by each vaccine and to identify immune markers of protection to enable prognostication of people who are at risk of severe complications from COVID-19.

Keywords: COVID-19; IgG; Omicron; SARS-CoV-2; memory B cell; neutralizing antibody.

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Conflict of interest statement

M.C.v.Z. and R.O.H. are inventors on a patent application related to generation of fluorescently labeled antigen tetramers used for flow cytometric analysis of antigen-specific B cells. The other authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1.
Figure 1.. SARS-CoV-2 structural components and binding to human ACE2 receptor via the Spike RBD.
The SARS-CoV-2 virus is composed of four main structural proteins: the Spike, Membrane, Envelope and Nucleocapsid. It carries a single-stranded RNA genome, which is encapsulated by a lipid envelope. The receptor-binding domain of the Spike protein binds to the human ACE2 receptor, allowing entry into host cells. ACE2, angiotensin converting enzyme 2; RBD, receptor-binding domain; ssRNA, single-stranded RNA. Created with BioRender.com.
Figure 2.
Figure 2.. The different pathways of the humoral immune response generate plasmablasts, Bmem, and LLPC.
Following activation, B cells follow either the T-independent or dependent pathways, depending on the structure of their cognate antigen. (A) The T-independent response generates plasmablasts, IgM+IgD+CD27+ and IgA+CD27− Bmem. (B) The GC response is T-dependent and produces both LLPC and Bmem, which increase in CD27 expression and SHM levels upon re-entry. (C) The T-dependent extrafollicular response is GC-independent and generates short-lived plasmablasts which produce low-affinity antibody. Th, helper T cell; Tfh, follicular helper T cell; SHM, somatic hypermutation; GC, germinal center; fDC, follicular dendritic cell; LLPC, long-lived plasma cell. Based on information from [26,30,34–36]. Created with BioRender.com.
Figure 3.
Figure 3.. Kinetics of RBD-specific IgG, IgM, and IgA levels and plasmablast and Bmem numbers in SARS-CoV-2 convalescence.
RBD-specific IgG levels decline following a peak at 2–4 weeks PSO but remain at detectable levels, whereas IgA and IgM levels drop more rapidly. Plasmablasts decrease after reaching peak levels ∼2 weeks PSO. RBD-specific Bmem numbers significantly increase in the months following infection, remaining at stable levels at least 6–8 months PSO. PSO, post-symptom onset; Bmem, memory B cells; Abs, antibodies; RBD, receptor-binding domain. Drawn in the style of Röltgen and Boyd [35], based on information from [41,43,45,50–52]. Created with BioRender.com.
Figure 4.
Figure 4.. SARS-CoV2 mRNA and adenoviral vector vaccine designs.
Adenoviral vector vaccines such as ChAdOx1 or Ad26.COV2.S comprise adenoviral vectors encapsulating the SARS-CoV-2 Spike protein DNA. When the vector is internalized into the host cell, the DNA is inserted into the nucleus where it is transcribed into mRNA before being translated into the Spike protein. mRNA vaccines such as BNT162b2 or mRNA-1273 comprise lipid nanoparticles containing Spike protein mRNA, which are internalized by recipient cells where the mRNA in is simply translated in the cytoplasm. The full-length Spike protein generated from either vaccine type can then be (A) processed and presented in MHC Classes I and II, (B) expressed on the cell surface, or (C) secreted from the cells, where it becomes a _target for the immune system. MHC, major histocompatibility complex. Based on information from [62]. Created with BioRender.com.
Figure 5.
Figure 5.. Kinetics of the antigen-specific antibody and Bmem response to mRNA vaccines up to 6 months post-vaccination.
The Spike- and RBD-specific IgG response is boosted by each vaccine dose, and peaks 1 week post-dose two, before declining. RBD-specific Bmem increase in the months following vaccination and remain at stable levels at least 6 months post-dose one. Bmem are of a class-switched resting phenotype and increase in Ig affinity over time. RBD, receptor-binding domain; Bmem, memory B cells. Based on information from [82,83]. Created with BioRender.com.
Figure 6.
Figure 6.. Relative escape of SARS-CoV-2 VoC from neutralization by sera from recipients of two mRNA vaccine doses.
Each of the five main past and present VoC escape neutralization by vaccine-elicited sera to varying degrees. NAb titers against Alpha are, on average, 2.75 times lower compared with those against Wuhan [106,119–122], those against Beta are 6.74-fold [106,109,112,119,120,122,123], those against Gamma are 3.43-fold [109,120,124], those against Delta are 3.76-fold [106,119–123], and those against Omicron are 56.50-fold lower [107,119,123,125]. Values are presented as mean fold change compared with Wuhan, error bars represent the range of the referenced studies. Total number of serum samples from pooled publications indicated. NAb, neutralizing antibodies; RBD, receptor-binding domain; VoC, variants of concern.
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