C-103 Special lecture: Beyond Neutralization is Metaneutralization

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Emerging viruses of high if intermittent concern for human health (exemplified here by filoviruses, alphaviruses, flaviviruses, and poxviruses) tend to cause acute and—unlike HIV—relatively non-persistent infections. While complete prevention of infection by vaccines is goalworthy, mitigation of viral burden is generally sufficient. Antibodies play a prominent role in both short-term and lasting immunity; however, these viruses also demonstrate how the complexities of antibody-mediated resistance to viral infection, disease, and spread are under-served by the common language of virology, in which assay-based terms such as neutralization and ADCC (antibody-dependent cell-mediated cytotoxicity) promote unhelpful oversimplifications of the in vivo phenomena they are intended to describe. For instance, it is widely inferred in error that something called neutralization is reliably necessary and sufficient for antibody-mediated protection against viruses. The roles and targets of antibodies against Ebola/Marburg, Sindbis/chikungunya, dengue/Zika and vaccinia/monkeypox viruses serve to contradict simple views. To provoke and expand new language among experts for whom nuance and complexity matter greatly (especially those involved in research on and development of vaccines and antibody-based therapies), the term metaneutralization is used here to encompass all mechanisms (entry-level neutralization, ADCC, and other) resident in antiviral protection observed empirically when monoclonal or polyclonal antibodies are administered before or after viral infection of an animal. For all mechanisms, appropriate Fc type and optimal Fc–FcR interactions appear helpful—often decisive—in favorable outcomes.

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