Post by Nadica (She/Her) on Sept 4, 2024 23:42:00 GMT
Hybrid immunity to SARS-CoV-2 arises from serological recall of IgG antibodies distinctly imprinted by infection or vaccination - Published Aug 20, 2024
Nadi's Note: While I'm firm in my belief that hybrid immunity to covid is a pipe dream due to the rapid mutation of viruses in circulation and their incredible ability to escape immune responses through that evolution, this article talks at length about an antibody that protects from all known strains of covid and could possibly be replicated for therapeutic purposes.
Highlights
•Infection and vaccination imprint distinct IgG responses at the molecular level
•Immunological imprinting varies between infection (S2/NTD) and vaccination (RBD)
•Over 60% of the IgG recall in hybrid immunity originates from the initial exposure
•Hybrid immune IgG plasma mAbs have superior neutralization potency and breadth
Summary
We describe the molecular-level composition of polyclonal immunoglobulin G (IgG) anti-spike antibodies from ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, vaccination, or their combination (“hybrid immunity”) at monoclonal resolution. Infection primarily triggers S2/N-terminal domain (NTD)-reactive antibodies, whereas vaccination mainly induces anti-receptor-binding domain (RBD) antibodies. This imprint persists after secondary exposures wherein >60% of ensuing hybrid immunity derives from the original IgG pool. Monoclonal constituents of the original IgG pool can increase breadth, affinity, and prevalence upon secondary exposures, as exemplified by the plasma antibody SC27. Following a breakthrough infection, vaccine-induced SC27 gained neutralization breadth and potency against SARS-CoV-2 variants and zoonotic viruses (half-maximal inhibitory concentration [IC50] ∼0.1–1.75 nM) and increased its binding affinity to the protective RBD class 1/4 epitope (dissociation constant [KD] < 5 pM). According to polyclonal escape analysis, SC27-like binding patterns are common in SARS-CoV-2 hybrid immunity. Our findings provide a detailed molecular definition of immunological imprinting and show that vaccination can produce class 1/4 (SC27-like) IgG antibodies circulating in the blood.
Graphical abstract
Nadi's Note: While I'm firm in my belief that hybrid immunity to covid is a pipe dream due to the rapid mutation of viruses in circulation and their incredible ability to escape immune responses through that evolution, this article talks at length about an antibody that protects from all known strains of covid and could possibly be replicated for therapeutic purposes.
Highlights
•Infection and vaccination imprint distinct IgG responses at the molecular level
•Immunological imprinting varies between infection (S2/NTD) and vaccination (RBD)
•Over 60% of the IgG recall in hybrid immunity originates from the initial exposure
•Hybrid immune IgG plasma mAbs have superior neutralization potency and breadth
Summary
We describe the molecular-level composition of polyclonal immunoglobulin G (IgG) anti-spike antibodies from ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, vaccination, or their combination (“hybrid immunity”) at monoclonal resolution. Infection primarily triggers S2/N-terminal domain (NTD)-reactive antibodies, whereas vaccination mainly induces anti-receptor-binding domain (RBD) antibodies. This imprint persists after secondary exposures wherein >60% of ensuing hybrid immunity derives from the original IgG pool. Monoclonal constituents of the original IgG pool can increase breadth, affinity, and prevalence upon secondary exposures, as exemplified by the plasma antibody SC27. Following a breakthrough infection, vaccine-induced SC27 gained neutralization breadth and potency against SARS-CoV-2 variants and zoonotic viruses (half-maximal inhibitory concentration [IC50] ∼0.1–1.75 nM) and increased its binding affinity to the protective RBD class 1/4 epitope (dissociation constant [KD] < 5 pM). According to polyclonal escape analysis, SC27-like binding patterns are common in SARS-CoV-2 hybrid immunity. Our findings provide a detailed molecular definition of immunological imprinting and show that vaccination can produce class 1/4 (SC27-like) IgG antibodies circulating in the blood.
Graphical abstract