1. Analysis of Archival Sera From Norovirus-Infected Individuals Demonstrates That Cross-Blocking of Emerging Viruses Is Genotype-Specific.
- Author
-
Pilewski KA, Ford-Siltz LA, Tohma K, Kendra JA, Landivar M, and Parra GI
- Subjects
- Humans, Enzyme-Linked Immunosorbent Assay, Antibodies, Neutralizing immunology, Antibodies, Neutralizing blood, Disease Outbreaks, Adult, Norovirus immunology, Norovirus genetics, Caliciviridae Infections immunology, Caliciviridae Infections virology, Caliciviridae Infections epidemiology, Antibodies, Viral blood, Antibodies, Viral immunology, Genotype, Gastroenteritis virology, Gastroenteritis immunology, Cross Reactions immunology
- Abstract
Background: Rapidly evolving RNA viruses, such as human norovirus, generate extraordinary sequence diversity, posing a significant challenge to vaccine design. This diversity, coupled with short-lasting natural immunity, leads to reinfection throughout one's lifetime. How reexposure shapes humoral immunity to future norovirus strains remains incompletely understood., Methods: We profiled the antibody responses following 2 community gastroenteritis outbreaks with GII.2 and GII.6 noroviruses in 1971. Using diverse virus-like particles (VLPs), enzyme-linked immunosorbent assay (ELISA), and carbohydrate-blocking assays (surrogate for neutralization), we examined the antibody response at acute and convalescent timepoints following GII.6 infection., Results: Convalescent sera displayed strong homologous blocking, demonstrating a 5-fold increase in GII.6 carbohydrate blockade over acute samples, and broad blocking of diverse archival and modern GII.6 noroviruses. Convalescent sera displayed limited carbohydrate blocking of heterotypic VLPs, despite high ELISA binding titers. Select individuals developed broad cross-genotype blockade, but this response was established before the second outbreak. Finally, we applied a novel competitive carbohydrate-blocking assay to demonstrate the epitope specificity and discrete compartments of the neutralizing response., Conclusions: Our data show that infection generates narrow, focused immunity directed toward the infecting genotype. We did detect broad cross-blocking in specific individuals, but these responses could be attributed to diverse, genotype-specific antibodies predating GII.6 infection., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)
- Published
- 2024
- Full Text
- View/download PDF