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Antiviral neutralizing antibodies: from in vitro to in vivo activity.

ABSTRACT: 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.

SUBMITTER: Burton DR

PROVIDER: S-EPMC10108814 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Antiviral neutralizing antibodies: from in vitro to in vivo activity.

Burton Dennis R DR

Nature reviews. Immunology 20230417 11

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 effec ...[more]

PMID: 37069260

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Project description:Topically applied microbicides may play a critical role in preventing sexual transmission of human immunodeficiency virus type 1 (HIV-1); however, their efficacy can be compromised by amyloid fibrils present in semen, which significantly increase HIV-1 infectivity. This phenomenon may have contributed to the failure of most microbicide candidates in clinical settings. Understanding the impact of semen on microbicide effectiveness is thus crucial. In our study, we evaluated the influence of semen on the neutralizing activity of broadly neutralizing antibodies (bNAbs), including PG16, PGT121, 10-1074, 3BNC117, and VRC01, which are potential microbicide candidates. We found that semen enhances infection of HIV-1 transmitted/founder viruses but only marginally affects the neutralizing activity of tested antibodies, suggesting their potential for microbicide application. Our findings underscore the need to consider semen-mediated enhancement when evaluating and developing microbicides and highlight the potential of incorporating HIV-1 bNAbs in formulations to enhance efficacy and mitigate HIV-1 transmission during sexual encounters.IMPORTANCEThis study examined the impact of semen on the development of microbicides, substances used to prevent the transmission of HIV-1 during sexual activity. Semen contains certain components that can render the virus more infectious, posing a challenge to microbicide effectiveness. Researchers specifically investigated the effect of semen on a group of powerful antibodies called broadly neutralizing antibodies, which can neutralize a large spectrum of different HIV-1 variants. The results revealed that semen only had a minimal effect on the antibodies' ability to neutralize the virus. This is promising because it suggests that these antibodies could still be effective in microbicides, even in the presence of semen. Understanding this interaction is crucial for developing better strategies to prevent HIV-1 transmission. By incorporating the knowledge gained from this study, scientists can now focus on creating microbicides that consider the impact of semen, bringing us closer to more effective prevention methods.

Dataset Information

Antiviral neutralizing antibodies: from in vitro to in vivo activity.

Publications

Antiviral neutralizing antibodies: from in vitro to in vivo activity.

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