A Game of Numbers

Abstract

The humoral response contributes to the protection against viral pathogens. Although antibodies have the potential to inhibit viral infections via several mechanisms, an ability to neutralize viruses directly may be particularly important. Neutralizing antibody titers are commonly used as predictors of protection from infection, especially in the context of vaccine responses and immunity. Despite the simplicity of the concept, how antibody binding results in virus inactivation is incompletely understood despite decades of research. Flaviviruses have been an attractive system in which to seek a structural and quantitative understanding of how antibody interactions with virions modulate infection because of the contribution of antibodies to both protection and pathogenesis. This review will present a stoichiometric model of antibody-mediated neutralization of flaviviruses and discuss how these concepts can inform the development of vaccines and antibody-based therapeutics.

Broadly Neutralizing Activity of Zika Virus-Immune Sera Identifies a Single Viral Serotype

“…While the existence of a single serotype was suggested by conservation of E protein sequences among ZIKV strains, factors that define the sensitivity of flaviviruses to neutralization remain incompletely understood (Pierson and Diamond, 2015). A recent study of the functional complexity of DENV vaccine-immune sera demonstrated that changes at only two amino acids were sufficient to render DENV1 and DENV2 RVPs equally sensitive to neutralization by monovalent DENV1 immune sera (VanBlargan et al, 2013).…”

Detection of Neutralizing Antibodies to Tembusu Virus: Implications for Infection and Immunity

“…Humoral immune response plays a significant role in protection of the host from flavivirus infections (1). Generally, neutralizing antibodies are thought to be the key mediators of protection against flaviviruses following both infection and vaccination (2,3).…”

Antibodies to SARS-CoV-2 and Their Potential for Therapeutic Passive Immunization

“…Antibodies can also exacerbate viral infection by different mechanisms that have long been described (55). In the vaccine context, infection by alpha-and flaviviruses (such as Dengue and Zika viruses) is enhanced when the antibody occupancy on the virion-surface epitopes falls below a critical threshold (56). This is the stoichiometric condition of an Fc-receptor-dependent form of ADE: the same antibodies that mediate ADE can be neutralizing and protective at higher occupancies on virions (56,57).…”