Review Article | Published:

Passive immunotherapy of viral infections: 'super-antibodies' enter the fray

Nature Reviews Immunology volume 18, pages 297308 (2018) | Download Citation

Abstract

Antibodies have been used for more than 100 years in the therapy of infectious diseases, but a new generation of highly potent and/or broadly cross-reactive human monoclonal antibodies (sometimes referred to as 'super-antibodies') offers new opportunities for intervention. The isolation of these antibodies, most of which are rarely induced in human infections, has primarily been achieved by large-scale screening for suitable donors and new single B cell approaches to human monoclonal antibody generation. Engineering the antibodies to improve half-life and effector functions has further augmented their in vivo activity in some cases. Super-antibodies offer promise for the prophylaxis and therapy of infections with a range of viruses, including those that are highly antigenically variable and those that are newly emerging or that have pandemic potential. The next few years will be decisive in the realization of the promise of super-antibodies.

Key points

  • Antibodies have been used for over a century prophylactically and, less often, therapeutically against viruses.

  • 'Super-antibodies' — a new generation of highly potent and/or broadly cross-reactive human monoclonal antibodies — offer new opportunities for prophylaxis and therapy of viral infections.

  • Super-antibodies are typically generated infrequently and/or in a limited number of individuals during natural infections.

  • Isolation of these antibodies has primarily been achieved by large-scale screening for suitable donors and new single B cell approaches to human monoclonal antibody generation.

  • Super-antibodies may offer the possibility of treating multiple viruses of a given family with a single reagent. They are also valuable templates for rational vaccine design.

  • The great potency of super-antibodies has many advantages for practical development as therapeutic reagents. These advantages can be enhanced by a variety of antibody engineering technologies.

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Acknowledgements

The authors thank J. Mascola, D. Sok and M. Vasquez for comments on the manuscript. The authors also thank L. Hangartner and C. Corbaci for assistance with figure preparation. D.R.B. acknowledges the financial support from the US National Institute of Allergy and Infectious Disease, the International AIDS Vaccine Initiative, the Bill and Melinda Gates Foundation and the Ragon Institute.

Author information

Affiliations

  1. Adimab LLC, Lebanon, New Hampshire 03766, USA.

    • Laura M. Walker
  2. Department of Immunology and Microbiology, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA.

    • Dennis R. Burton
  3. International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037, USA.

    • Dennis R. Burton
  4. Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02139, USA.

    • Dennis R. Burton

Authors

  1. Search for Laura M. Walker in:

  2. Search for Dennis R. Burton in:

Contributions

Both authors contributed to research and discussion of the content of the article and to writing, reviewing and editing of the manuscript before submission.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Laura M. Walker or Dennis R. Burton.

Glossary

Humanized mouse antibodies

Genetically engineered mouse antibodies in which the protein sequence has been modified to increase its similarity to human antibodies, thereby decreasing its potential immunogenicity.

Transchromosomal cows

Cows that have been genetically modified to incorporate human chromosomes so that upon immunization they generate human antibodies.

Antibody-dependent cellular cytotoxicity

(ADCC). A mechanism by which Fc receptor-bearing effector cells such as natural killer (NK) cells recognize and kill antibody-coated target cells, such as virus-infected cells. The Fc portions of the coating antibodies interact with an Fc receptor (for example, FcγRIII; which is expressed by NK cells), thereby initiating a signalling cascade that results in the release of cytotoxic granules (containing perforin and granzyme B) from the effector cell, which lead to cell death of the antibody-coated cell.

Complement-dependent cytotoxicity

A mechanism of antibody-mediated immunity whereby the association of an antibody on a target cell surface leads to binding of the complement component C1q and triggering of the classical complement cascade. The cascade leads to elimination of target cells by a number of mechanisms, including the formation of the membrane attack complex, the cytolytic end product of the complement cascade.

Hyperimmune globulins

Antibody preparations generated from plasma of donors with high titres of an antibody against a specific pathogen or antigen. Hyperimmune globulins are available against rabies virus, hepatitis B virus and varicella zoster virus, among other viruses.

About this article

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DOI

https://doi.org/10.1038/nri.2017.148