The role of anti‐flavivirus humoral immune response in protection and pathogenesis

Abstract

SummaryFlavivirus infections are a public health threat in the world that requires the development of safe and effective vaccines. Therefore, the understanding of the anti‐flavivirus humoral immune response is fundamental to future studies on flavivirus pathogenesis and the design of anti‐flavivirus therapeutics. This review aims to provide an overview of the current understanding of the function and involvement of flavivirus proteins in the humoral immune response as well as the ability of the anti‐envelope (anti‐E) antibodies to interfere (neutralizing antibodies) or not (non‐neutralizing antibodies) with viral infection, and how they can, in some circumstances enhance dengue virus infection on Fc gamma receptor (FcγR) bearing cells through a mechanism known as antibody‐dependent enhancement (ADE). Thus, the dual role of the antibodies against E protein poses a formidable challenge for vaccine development. Also, we discuss the roles of antibody binding stoichiometry (the concentration, affinity, or epitope recognition) in the neutralization of flaviviruses and the “breathing” of flavivirus virions in the humoral immune response. Finally, the relevance of some specific antibodies in the design and improvement of effective vaccines is addressed.

A Yellow Fever Virus 17D Infection and Disease Mouse Model Used to Evaluate a Chimeric Binjari-Yellow Fever Virus Vaccine

“…The structural proteins of flaviviruses comprise two proteins, envelope (E) and membrane (M), with the latter synthesized as a precursor (prM), collectively referred to as prME [ 21 ]. Neutralizing antibodies directed at E are believed to represent the primary mediators of protection for most flavivirus vaccines, including YFV vaccines [ 22 , 23 ]. We recently described a new chimeric flavivirus vaccine platform based on the insect specific flavivirus Binjari virus [ 24 , 25 ].…”

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

“…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). The in vitro observations of ADE seem to account for the unfortunate outcome of recent Dengue vaccine trials, where examples of worsened disease postinfection occurred (58). ADE has been reported in the CoV literature, although there is no strong evidence that it will be as problematic as for alpha-and flaviviruses (59)(60)(61)(62)(63)(64).…”

Antibodies to SARS-CoV-2 and their potential for therapeutic passive immunization

“…This is the stoichiometric condition of an Fc-receptor-dependent form of ADE: the same antibodies that mediate ADE can neutralize and protect at higher occupancies on virions; alternatively, non-NAbs binding to epitopes exposed on the virion surface to antigens that are not functional for mediating entry may confer ADE (Pierson and Diamond, 2015;Klasse, 2014). The in vitro observations of ADE seem to account for the unfortunate outcome of recent Dengue vaccine trials with examples of worsened disease post-infection (Hurtado-Monzó n et al, 2020). ADE has been reported in the coronavirus literature, although most studies do not suggest that it will be as problematic as for alpha-and flaviviruses (Jaume et al, 2011;Kam et al, 2007;Peeples, 2020;Wan et al, 2020;Wang et al, 2014;Wang et al, 2016;Diamond and Pierson, 2020;de Alwis et al, 2020;Burton and Walker, 2020).…”