Antibody imprinting is well recognized, yet its long-term dynamics and epitope specificity remain poorly understood. Here, we studied individuals sequentially infected with SARS-CoV-1 (SARS-1) and SARS-CoV-2 (SARS-2) over two decades and found durable imprinting of antibody responses following SARS-2 BF.7 breakthrough infection. Approximately 60% of isolated monoclonal antibodies were SARS-1 imprinted and targeted conserved receptor-binding domain regions, whereas 37% overcame imprinting to recognize the SARS-2 receptor-binding motif overlapping the ACE2-binding site. Notably, some SARS-1-only antibodies retained germline-like features and neutralizing activity 20 years after infection. One exceptionally imprinted broadly neutralizing antibody, THZ937, protected hamsters against contact and airborne transmission of Omicron EG.5.1, demonstrating the functional relevance of durable imprinted antibodies. Together, these findings define the remarkable longevity and molecular basis of antibody imprinting and provide insights for pan-sarbecovirus vaccine design.
ABSTRACT Bacteriocins are ribosomally synthesized antimicrobial peptides or proteins that offer an alternative to conventional antibiotics against multidrug‐resistant pathogens. Phage tail‐like bacteriocins (tailocins) are classified into rigid R‐type and flexible F‐type variants. While R‐type pyocins from Pseudomonas aeruginosa are well‐characterized, F‐type pyocins remain poorly understood, especially with respect to the molecular mechanisms for their Gram‐negative bactericidal activity. Here, we report cryo‐electron microscopy structures of the F‐type pyocin from P. aeruginosa ATCC 15442 at 2.29–3.26 Å resolution, encompassing three modular components: the tail cap, tail tip, and tail fiber. Structural comparisons with bacteriophage λ reveal a conserved tail tip architecture, including the baseplate hub proteins, distal tail protein, tail assembly protein, and tape measure protein. Unexpectedly, we identify three trimeric side fibers that attach not to the distal tail protein, as in canonical systems, but to the α‐helical shaft of the central fiber, indicating a previously unrecognized attachment mode. The receptor‐binding domain of the side fiber shares structural similarity with LPS‐recognizing domains of R‐type pyocins. Together, these results define the structural basis of F‐type pyocin assembly and host recognition, reveal conserved and unique features relative to phage λ, and provide a framework for engineering tailocins as precision antimicrobials against drug‐resistant P. aeruginosa.
Zhiwei Gu, Yufan Xie, Lanxin Wang et al.· Advancement of science· 0 citations
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