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Review
. 2024 Apr 3;13(2):28.
doi: 10.3390/antib13020028.

Beyond bNAbs: Uses, Risks, and Opportunities for Therapeutic Application of Non-Neutralising Antibodies in Viral Infection

Kahlio Mader  1 , Lynn B Dustin  1
Affiliations
Review

Beyond bNAbs: Uses, Risks, and Opportunities for Therapeutic Application of Non-Neutralising Antibodies in Viral Infection

Kahlio Mader et al. Antibodies (Basel). .

Abstract

The vast majority of antibodies generated against a virus will be non-neutralising. However, this does not denote an absence of protective capacity. Yet, within the field, there is typically a large focus on antibodies capable of directly blocking infection (neutralising antibodies, NAbs) of either specific viral strains or multiple viral strains (broadly-neutralising antibodies, bNAbs). More recently, a focus on non-neutralising antibodies (nNAbs), or neutralisation-independent effects of NAbs, has emerged. These can have additive effects on protection or, in some cases, be a major correlate of protection. As their name suggests, nNAbs do not directly neutralise infection but instead, through their Fc domains, may mediate interaction with other immune effectors to induce clearance of viral particles or virally infected cells. nNAbs may also interrupt viral replication within infected cells. Developing technologies of antibody modification and functionalisation may lead to innovative biologics that harness the activities of nNAbs for antiviral prophylaxis and therapeutics. In this review, we discuss specific examples of nNAb actions in viral infections where they have known importance. We also discuss the potential detrimental effects of such responses. Finally, we explore new technologies for nNAb functionalisation to increase efficacy or introduce favourable characteristics for their therapeutic applications.

Keywords: Fc receptors; antibody engineering; antiviral immunity; immunoglobulin; neutralizing antibodies; viral infection.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Non-neutralising antibody activities. Antibody-Mediated Complement Deposition (AMCD), Antibody-Dependent Cellular Phagocytosis (ADCP), Antibody-Dependent Cellular Cytotoxicity (ADCC). Key of icons is shown on the right. Created with Biorender.com, accessed 26 March 2024.
Figure 2
Figure 2
Simplified schematic of potential deleterious effects of antibody responses. Antibody Dependent Enhancement (ADE). Key of icons is shown on the right. Created with Biorender.com, accessed 26 March 2024.
Figure 3
Figure 3
Simplified schematic depicting innovative potential functionalisation opportunities of non-neutralising antibodies. Site Directed Mutagenesis (SDM). Created with Biorender.com, accessed 26 March 2024.
See this image and copyright information in PMC

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