2025-03-06 テキサス大学オースチン校 (UT Austin)
<関連情報>
- https://news.utexas.edu/2025/03/06/research-identifies-key-antibodies-for-development-of-broadly-protective-norovirus-vaccine/
- https://www.science.org/doi/10.1126/scitranslmed.ads8214
パンデミックGII.4変異体またはヒトノロウイルスの7つのGII遺伝子型を標的とする広範な中和抗体 Broadly neutralizing antibodies targeting pandemic GII.4 variants or seven GII genotypes of human norovirus
Juyeon Park, Lisa C. Lindesmith, Adam S. Olia, Veronica P. Costantini, […], and Ralph S. Baric
Science Translational Medicine Published:5 Mar 2025
Editor’s summary
Human norovirus is a major cause of infectious gastroenteritis. Although most individuals recover after a few unpleasant days, older individuals, young children, and those in immunocompromised states may be at risk of severe disease. A major challenge with vaccinating against norovirus is that there is substantial genetic diversity between variants and across viral genotypes. Here, Park et al. analyzed serum from two recipients of an oral adenoviral-vectored norovirus vaccine, both of whom had robust responses to the vaccine. One participant elicited antibodies that could neutralize several viral variants within a genotype, whereas the other developed antibodies that could neutralize across genotypes. Deeper analysis of one antibody, VX22, revealed that it targeted a conserved region on the VP1 capsid. This study provides proof-of-concept data that norovirus vaccines can elicit broadly neutralizing antibodies and further highlights a region of the virus that, when incorporated into a vaccine, may achieve that goal. —Courtney Malo
Abstract
Human norovirus causes more than 700 million illnesses annually. Extensive genetic diversity and a paucity of information on conserved neutralizing epitopes pose major obstacles to the design of broadly protective norovirus immunogens. Here, we used high-resolution liquid chromatography–tandem mass spectrometry (LC-MS/MS)–driven proteomics to quantitatively characterize the circulating serum IgG repertoire before and after immunization with an experimental monovalent norovirus GII.4 VP1 capsid–encoding adenoviral vaccine. Two participants were specifically selected on the basis of the breadth of serum neutralization responses either across GII.4 variants (participant A) or across GII genotypes (participant B). In participant A, vaccination back-boosted highly abundant serum antibody clonotypes targeting epitopes conserved among rapidly evolving GII.4 variants spanning from a strain identified in 1987 to a strain identified in 2019. In participant B, we identified a recall response consisting of broadly neutralizing monoclonal antibodies with remarkable cross-GII ligand-binding blockade (blocking ≥ seven GII genotypes) and virus neutralization breadth. The cocrystal structure of one of these antibodies, VX22, in complex with the VP1 capsid protruding (P) domain revealed a highly conserved epitope (residues 479 to 484 and 509 to 513) within two lateral loops of the P1 subdomain. Antibody evolutionary trajectory analysis further revealed that VX22 had originally evolved from an early heterologous infection, likely by a GII.12 strain. Together, our study demonstrates that norovirus human monoclonal antibodies with broad GII.4 potency and cross-GII breadth can be boosted in serum after immunization with an adenoviral vector–based vaccine, findings that may guide the design of immunogens for broadly protective norovirus vaccines.
