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Antiviral neutralizing antibodies: from in vitro to in vivo activity

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NATURE REVIEWS IMMUNOLOGY
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NATURE PORTFOLIO
DOI: 10.1038/s41577-023-00858-w

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Neutralizing antibodies (nAbs) have become increasingly important in preventing and treating viral infections and guiding vaccine development. In vivo, nAbs can block viral entry to target cells and exert antiviral effects against viruses and infected cells. Interpreting in vivo results based on in vitro assays is challenging but crucial in choosing the most effective antibody and vaccine strategies. This review discusses the assays for and mechanisms of neutralizing antibodies against viruses as tools to understand and predict their activity in vivo when administered passively or induced by vaccination or infection.
Neutralizing antibodies (nAbs) are being increasingly used as passive antiviral reagents in prophylactic and therapeutic modalities and to guide viral vaccine design. In vivo, nAbs can mediate antiviral functions through several mechanisms, including neutralization, which is defined by in vitro assays in which nAbs block viral entry to target cells, and antibody effector functions, which are defined by in vitro assays that evaluate nAbs against viruses and infected cells in the presence of effector systems. Interpreting in vivo results in terms of these in vitro assays is challenging but important in choosing optimal passive antibody and vaccine strategies. Here, I review findings from many different viruses and conclude that, although some generalizations are possible, deciphering the relative contributions of different antiviral mechanisms to the in vivo efficacy of antibodies currently requires consideration of individual antibody-virus interactions. Assays for, and mechanisms of action of, neutralizing antibodies against viruses are considered here as tools to interpret and predict the activity of such antibodies in vivo, administered passively or induced by vaccination or infection.

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