Antibody-Dependent Enhancement Activity of a Plant-Made Vaccine against West Nile Virus

Sun, Haiyan; Acharya, Dhiraj; Paul, Amber M.; Lai, Huafang; He, Jialong; Bai, Fengwei; Chen, Qiang

doi:10.3390/vaccines11020197

Cited by 10 publications

(5 citation statements)

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“…The potential impact of N-linked glycosylation variation on the enhancement of DENV and ZIKV infection by ZV1 was investigated in an in vitro assay. As shown in Figure 3, ZV1 CHO triggered ADE of DENV (Figure 3A) infection in K562 cells that express the human FcγRIIa, a phenomenon observed for CHO-cell-produced mAbs in previous studies [31,38]. Similarly, ZV1 CHO also promoted the ADE of ZIKV effectively (Figure 3B).…”

Section: Antibody-dependent Enhancement Of Denv and Zikv Infection By...supporting

confidence: 63%

Plant-Produced Anti-Zika Virus Monoclonal Antibody Glycovariant Exhibits Abrogated Antibody-Dependent Enhancement of Infection

et al. 2023

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Monoclonal antibodies (mAb) against the envelope (E) protein of Zika virus (ZIKV) have shown great potential as therapeutics against the Zika epidemics. However, their use as a therapy may predispose treated individuals to severe infection by the related dengue virus (DENV) via antibody-dependent enhancement of infection (ADE). Here, we generated a broadly neutralizing flavivirus mAb, ZV1, with an identical protein backbone but different Fc glycosylation profiles. The three glycovariants, produced in wild-type (WT) and glycoengineered ΔXF Nicotiana benthamiana plants and in Chinese hamster ovary cells (ZV1WT, ZV1ΔXF, and ZV1CHO), respectively, showed equivalent neutralization potency against both ZIKV and DENV. By contrast, the three mAb glycoforms demonstrated drastically different ADE activity for DENV and ZIKV infection. While ZV1CHO and ZV1ΔXF showed ADE activity upon DENV and ZIKV infection, ZV1WT totally forwent its ADE. Importantly, all three glycovariants exhibited antibody-dependent cellular cytotoxicity (ADCC) against virus-infected cells, with increased potency by the fucose-free ZV1ΔXF glycoform. Moreover, the in vivo efficacy of the ADE-free ZV1WT was demonstrated in a murine model. Collectively, we demonstrated the feasibility of modulating ADE by Fc glycosylation, thereby establishing a novel approach for improving the safety of flavivirus therapeutics. Our study also underscores the versatile use of plants for the rapid expression of complex human proteins to reveal novel insight into antibody function and viral pathogenesis.

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Section: Antibody-dependent Enhancement Of Denv and Zikv Infection By...supporting

confidence: 63%

Plant-Produced Anti-Zika Virus Monoclonal Antibody Glycovariant Exhibits Abrogated Antibody-Dependent Enhancement of Infection

et al. 2023

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“…The plaques were stained with 0.1% Neutral red solution (Sigma) and counted 68 . Then the PRNT 50 values were calculated with GraphPad Prism software (version 7.0) 72 .…”

Section: Methodsmentioning

confidence: 99%

An effective live-attenuated Zika vaccine candidate with a modified 5′ untranslated region

et al. 2023

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Zika virus (ZIKV) is a mosquito-transmitted flavivirus that has caused devastating congenital Zika syndrome (CZS), including microcephaly, congenital malformation, and fetal demise in human newborns in recent epidemics. ZIKV infection can also cause Guillain-Barré syndrome (GBS) and meningoencephalitis in adults. Despite intensive research in recent years, there are no approved vaccines or antiviral therapeutics against CZS and adult Zika diseases. In this report, we developed a novel live-attenuated ZIKV strain (named Z7) by inserting 50 RNA nucleotides (nt) into the 5′ untranslated region (UTR) of a pre-epidemic ZIKV Cambodian strain, FSS13025. We used this particular ZIKV strain as it is attenuated in neurovirulence, immune antagonism, and mosquito infectivity compared with the American epidemic isolates. Our data demonstrate that Z7 replicates efficiently and produces high titers without causing apparent cytopathic effects (CPE) in Vero cells or losing the insert sequence, even after ten passages. Significantly, Z7 induces robust humoral and cellular immune responses that completely prevent viremia after a challenge with a high dose of an American epidemic ZIKV strain PRVABC59 infection in type I interferon (IFN) receptor A deficient (Ifnar1−/−) mice. Moreover, adoptive transfer of plasma collected from Z7 immunized mice protects Ifnar1−/− mice from ZIKV (strain PRVABC59) infection. These results suggest that modifying the ZIKV 5′ UTR is a novel strategy to develop live-attenuated vaccine candidates for ZIKV and potentially for other flaviviruses.

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“…The development and approval of human vaccines face several limitations, including economic considerations, particularly for USUV, given that it has been implicated in only a limited number of human cases. Those limitations also include safety concerns, particularly the potential risk of antibody-dependent enhancement (ADE) with other orthoflaviviruses, such as Zika Virus or Dengue Virus [ 90 ]. The question of potential ADE effects or cross-protection also arises between WNV and USUV, notably due to their phylogenetic proximity and the fact that they co-circulate in the same geographic regions.…”

Section: Main Challenges To Overcomementioning

confidence: 99%

Circulation of West Nile Virus and Usutu Virus in Europe: Overview and Challenges

Simonin

2024

Viruses

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West Nile Virus (WNV) and Usutu Virus (USUV) are both neurotropic mosquito-borne viruses belonging to the Flaviviridae family. These closely related viruses mainly follow an enzootic cycle involving mosquitoes as vectors and birds as amplifying hosts, but humans and other mammals can also be infected through mosquito bites. WNV was first identified in Uganda in 1937 and has since spread globally, notably in Europe, causing periodic outbreaks associated with severe cases of neuroinvasive diseases such as meningitis and encephalitis. USUV was initially isolated in 1959 in Swaziland and has also spread to Europe, primarily affecting birds and having a limited impact on human health. There has been a recent expansion of these viruses’ geographic range in Europe, facilitated by factors such as climate change, leading to increased human exposure. While sharing similar biological traits, ecology, and epidemiology, there are significant distinctions in their pathogenicity and their impact on both human and animal health. While WNV has been more extensively studied and is a significant public health concern in many regions, USUV has recently been gaining attention due to its emergence in Europe and the diversity of its circulating lineages. Understanding the pathophysiology, ecology, and transmission dynamics of these viruses is important to the implementation of effective surveillance and control measures. This perspective provides a brief overview of the current situation of these two viruses in Europe and outlines the significant challenges that need to be addressed in the coming years.

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Antibody-Dependent Enhancement Activity of a Plant-Made Vaccine against West Nile Virus

Cited by 10 publications

References 50 publications

Plant-Produced Anti-Zika Virus Monoclonal Antibody Glycovariant Exhibits Abrogated Antibody-Dependent Enhancement of Infection

Plant-Produced Anti-Zika Virus Monoclonal Antibody Glycovariant Exhibits Abrogated Antibody-Dependent Enhancement of Infection

An effective live-attenuated Zika vaccine candidate with a modified 5′ untranslated region

Circulation of West Nile Virus and Usutu Virus in Europe: Overview and Challenges

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