Dengue virus specific IgY provides protection following lethal dengue virus challenge and is neutralizing in the absence of inducing antibody dependent enhancement

Abstract

Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are severe disease manifestations that can occur following sequential infection with different dengue virus serotypes (DENV1-4). At present, there are no licensed therapies to treat DENV-induced disease. DHF and DSS are thought to be mediated by serotype cross-reactive antibodies that facilitate antibody-dependent enhancement (ADE) by binding to viral antigens and then Fcγ receptors (FcγR) on target myeloid cells. Using genetically engineered DENV-specific antibodies, it has been shown that the interaction between the Fc portion of serotype cross-reactive antibodies and FcγR is required to induce ADE. Additionally, it was demonstrated that these antibodies were as neutralizing as their non-modified variants, were incapable of inducing ADE, and were therapeutic following a lethal, antibody-enhanced infection. Therefore, we hypothesized that avian IgY, which do not interact with mammalian FcγR, would provide a novel therapy for DENV-induced disease. We demonstrate here that goose-derived anti-DENV2 IgY neutralized DENV2 and did not induce ADE in vitro. Anti-DENV2 IgY was also protective in vivo when administered 24 hours following a lethal DENV2 infection. We were also able to demonstrate via epitope mapping that both full-length and alternatively spliced anti-DENV2 IgY recognized different epitopes, including epitopes that have not been previously identified. These observations provide evidence for the potential therapeutic applications of goose-derived anti-DENV2 IgY.

Egg yolk antibodies (IgY) and their applications in human and veterinary health: A review

“…In one year, a single laying hen produces between 17 and 35 g of total IgY [13]. Although the production of IgY for research is mainly done in chicken, other birds are also used for the same purpose, such as goose [57] and quail [58], using an immunization protocol similar to that used for chickens.…”

“…Another possible therapeutic use of specific IgY is against dengue fever, as demonstrated by Fink et al Anti-DENV2 IgY produced in goose was able to neutralize the virus in vitro and in vivo without binding to Fcγ receptors on myeloid cells and generating ADE (antibody dependent enhancement) in mice [57].…”

Antimicrobial Resistance: Its Surveillance, Impact, and Alternative Management Strategies in Dairy Animals

“…However, being proteinaceous in nature, IgY antibodies are sensitive to GIT stress and may be encapsulated while administering to mammalian gut ( 294 ). Recently, avian IgY has also been documented to render protection against dengue ( 295 ) and bursal disease virus ( 296 ). Available data from in vivo and clinical trials clearly points out their possibility to act as an alternate to current day antibiotics.…”

Codon optimization, expression in Escherichia coli, and immunogenicity analysis of deformed wing virus (DWV) structural protein

“…However, research on therapeutic drugs against DWV is still rare. Egg yolk antibodies known as immunoglobulin Y (IgY) have been widely utilized in the prevention and control of epidemic diseases associated with Acinetobacter baumannii, Vibrio splendidus, the Dengue virus, noroviruses, rotaviruses and duck adenovirus 3 (Fink et al, 2017;Ghosh, Malik & Kobayashi, 2017;Jahangiri et al, 2019;Li et al, 2016;Yin et al, 2019). Moreover, Sun et al (2018) reported that specific IgY could be obtained from hens immunized with an inactivated Chinese Sacbrood virus (CSBV) vaccine, which has the ability to neutralize CSBV.…”