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Antibody-Dependent Enhancement (ADE) is a complex and poorly understood phenomenon, likely underpinned by different mechanisms, where binding of a virus to suboptimal antibodies enhances severity of the disease, rather than providing protection to the host.
1/ https://twitter.com/DavidJWeber2/status/1334508495866109958
1/ https://twitter.com/DavidJWeber2/status/1334508495866109958
The aspect of ADE of most relevance in the context of #SARSCoV2 vaccination is sometime termed 'original antigenic sin' (OAS), a phenomenon where the clinical course of a disease is more severe in people having been previously immunised to the pathogen.
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The textbook example for 'original antigenic sin' (OAS) is dengue. The viral population is comprised of 4-5 genetically different lineages. Prior exposure to one lineage of dengue tends to make subsequent infections by another lineage more severe.
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https://elifesciences.org/articles/42496
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https://elifesciences.org/articles/42496
OAS induced by vaccination/reinfection is expected to be highest in the presence of distinct lineages of a pathogen generating imperfect 'cross-immunity', whereby the host immune system targets antigens of the initial virus/vaccine rather the one causing the current infection.
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The closest I'm aware of to OAS for #SARSCoV2 is an observation that prior exposure to the endemic 'common cold' HCoV OC43 might have lead to more severe symptoms in some cases.
5/ https://www.medrxiv.org/content/10.1101/2020.10.10.20210070v1
5/ https://www.medrxiv.org/content/10.1101/2020.10.10.20210070v1
The OAS risk of vaccination/reinfection by #SARSCoV2 itself feels very remote at this stage, as the entire viral population still has very low genetic diversity, with 2 strains being on average only ~12 mutations apart (<1 'immunologically meaningful').
6/ https://www.nature.com/articles/s41467-020-19818-2
6/ https://www.nature.com/articles/s41467-020-19818-2
The theoretical prediction of low risk of OAS in #SARSCoV2 vaccination/reinfection is supported by two bodies of preliminary but growing evidence: severity of symptoms upon reinfection, and efficacy of vaccines from phase III trials.
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There have probably been hundreds if not thousands of reinfections by #SARSCoV2 to date, the majority unreported. With the exception of the 'Nevada patient' case, none, to the best of my knowledge, led to more severe symptoms upon reinfection.
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A second line of evidence is that all vaccine clinical trials on #SARSCoV2 involving tenth of thousands of people have reported fewer severe cases in the vaccine arm than among the controls.
Both near-systematically milder symptoms upon reinfection, and lower occurrence of severe disease in the vaccine arm of #SARSCoV2 vaccine trials point to OAS being very events, at worst, irrespective of whether immunisation had been acquired through infection or vaccination.
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