The potential for antibody-dependent enhancement of SARS-CoV-2 infection: Translational implications for vaccine development

Abstract There is an urgent need for vaccines to the 2019 coronavirus (COVID19; SARS-CoV-2). Vaccine development may not be straightforward, due to antibody-dependent enhancement (ADE). Antibodies against viral surface proteins can, in some cases, increase infection severity by ADE. This phenomenon occurs in SARS-CoV-1, MERS, HIV, Zika, and dengue virus infection and vaccination. Lack of high-affinity anti-SARS-CoV-2 IgG in children may explain the decreased severity of infection in these groups. Here, we discuss the evidence for ADE in the context of SARS-CoV-2 infection and how to address this potential translational barrier to vaccine development, convalescent plasma, and targeted monoclonal antibody therapies.

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Potential Mechanisms of Age Related Severity of COVID-19 Infection: Implications for Development of Vaccines, Convalescent Serum, and Antibody Therapies

10.31219/osf.io/f3pze ◽

2020 ◽

Cited By ~ 3

Author(s):

Martin Zand ◽

Jiong Wang

Keyword(s):

Viral Entry ◽

Vaccine Development ◽

Surface Proteins ◽

Igg Antibodies ◽

Dengue Virus Infection ◽

Younger Adults ◽

High Affinity ◽

Age Related ◽

Coronavirus Infection ◽

Viral Surface

There is an urgent need for vaccines to induce immunity to the 2019 coronavirus strain (COVID-19; CoV-SARS-2). Vaccine development may not be straightforward, in part due to the the phenomenon of antibody-dependent enhancement (ADE). The immune response to coronavirus infection or vaccination generates a mixture of IgG antibodies against viral surface proteins. Many of these antibodies block viral infection. However, in some cases IgG:virus complexes can facilitate viral entry and infection of cells by ADE, increasing the the risk and severity of infection. This phenomenon occurs in SARS, MERS, HIV, Zika and dengue virus infection and vaccination; it has been a serious barrier to vaccine development for these infections. Lack of high-affinity anti-COVID-19 IgG antibodies in children and younger adults may explain, in part, the decreased severity of infection in these groups. Here, we discuss the evidence for ADE in the context of COVID-19 infection, and how it may affect development of a vaccine and convalescent serum therapies. Here we discuss ADE in the context of COVID-19 infection, and how this may affect vaccine development, convalescent serum, and targeted monoclonal antibody therapies. We caution that this work is a hypothesis, and should be taken as such.

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Involvement of the Fc receptor IIA cytoplasmic domain in antibody-dependent enhancement of dengue virus infection

Journal of General Virology ◽

10.1099/vir.0.014829-0 ◽

2009 ◽

Vol 91 (1) ◽

pp. 103-111 ◽

Cited By ~ 40

Author(s):

M. L. Moi ◽

C.-K. Lim ◽

T. Takasaki ◽

I. Kurane

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Cytoplasmic Domain ◽

Fc Receptor ◽

Dengue Virus Infection ◽

Antibody Dependent Enhancement

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Current Understanding of the Pathogenesis of Dengue Virus Infection

Current Microbiology ◽

10.1007/s00284-020-02284-w ◽

2020 ◽

Author(s):

Puneet Bhatt ◽

Sasidharan Pillai Sabeena ◽

Muralidhar Varma ◽

Govindakarnavar Arunkumar

Keyword(s):

Immune Response ◽

T Cells ◽

Virus Infection ◽

Dengue Virus ◽

Genetic Factors ◽

Host Immune Response ◽

Severe Dengue ◽

Ns1 Protein ◽

Dengue Virus Infection ◽

Antibody Dependent Enhancement

AbstractThe pathogenesis of dengue virus infection is attributed to complex interplay between virus, host genes and host immune response. Host factors such as antibody-dependent enhancement (ADE), memory cross-reactive T cells, anti-DENV NS1 antibodies, autoimmunity as well as genetic factors are major determinants of disease susceptibility. NS1 protein and anti-DENV NS1 antibodies were believed to be responsible for pathogenesis of severe dengue. The cytokine response of cross-reactive CD4+ T cells might be altered by the sequential infection with different DENV serotypes, leading to further elevation of pro-inflammatory cytokines contributing a detrimental immune response. Fcγ receptor-mediated antibody-dependent enhancement (ADE) results in release of cytokines from immune cells leading to vascular endothelial cell dysfunction and increased vascular permeability. Genomic variation of dengue virus and subgenomic flavivirus RNA (sfRNA) suppressing host immune response are viral determinants of disease severity. Dengue infection can lead to the generation of autoantibodies against DENV NS1antigen, DENV prM, and E proteins, which can cross-react with several self-antigens such as plasminogen, integrin, and platelet cells. Apart from viral factors, several host genetic factors and gene polymorphisms also have a role to play in pathogenesis of DENV infection. This review article highlights the various factors responsible for the pathogenesis of dengue and also highlights the recent advances in the field related to biomarkers which can be used in future for predicting severe disease outcome.

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