The following is a summary of “Analysis of Archival Sera from Norovirus-Infected Individuals Demonstrates that Cross-Blocking of Emerging Viruses is Genotype-Specific,” published in the February 2024 issue of Infectious Diseases by Pilewski et al.
Researchers conducted a retrospective study to investigate how the remarkable sequence diversity of rapidly evolving RNA viruses like human norovirus and transient natural immunity influence humoral immune responses upon re-exposure to shape future vaccine design strategies.
They analyzed antibody responses during two community gastroenteritis outbreaks caused by GII.2 and GII.6 noroviruses in 1971. Using various VLPs, ELISA, and carbohydrate-blocking assays (surrogate for neutralization), they investigated the antibody response at acute and convalescent stages after GII.6 infection.
The results revealed a robust homologous blocking effect in convalescent sera, indicating a 5-fold enhancement in GII.6 carbohydrate-blockade compared to acute samples. These sera demonstrated broad blocking activity against various archival and contemporary GII.6 noroviruses. Despite high ELISA binding titers, convalescent sera exhibited limited carbohydrate-blocking of heterotypic VLPs. Although certain individuals showed a broad cross-genotype blockade, this response was established before the second outbreak. A novel competitive carbohydrate-blocking assay was applied to showcase the epitope-specificity and distinct compartments of the neutralizing response.
Investigators concluded that while infection induces targeted immunity against the specific genotype, broad cross-blocking in some individuals likely reflects pre-existing, diverse antibodies, not genuine cross-protection.
Source: academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiae085/7612218