Virus Neutralisation: New Insights from Kinetic Neutralisation Curves

Carsten Magnus

PLOS Computational Biology, 2013, vol. 9, issue 2, 1-11

Abstract: Antibodies binding to the surface of virions can lead to virus neutralisation. Different theories have been proposed to determine the number of antibodies that must bind to a virion for neutralisation. Early models are based on chemical binding kinetics. Applying these models lead to very low estimates of the number of antibodies needed for neutralisation. In contrast, according to the more conceptual approach of stoichiometries in virology a much higher number of antibodies is required for virus neutralisation by antibodies. Here, we combine chemical binding kinetics with (virological) stoichiometries to better explain virus neutralisation by antibody binding. This framework is in agreement with published data on the neutralisation of the human immunodeficiency virus. Knowing antibody reaction constants, our model allows us to estimate stoichiometrical parameters from kinetic neutralisation curves. In addition, we can identify important parameters that will make further analysis of kinetic neutralisation curves more valuable in the context of estimating stoichiometries. Our model gives a more subtle explanation of kinetic neutralisation curves in terms of single-hit and multi-hit kinetics. Author Summary: How many antibodies have to bind to a virus particle such that it is prevented from infecting a cell? This seemingly simple question has not been answered yet. However, this number is crucial to determine whether a vaccine can stimulate the immune system to elicit enough antibodies to neutralise virus before starting an infection. Two different approaches have been applied to answer this question, leading to contradictory results. One approach is inspired by concepts from binding kinetics, the other approach is a more conceptual one. Here, I describe the advantages and disadvantages of either approaches and condense the advantages of both into one model framework. I show under which conditions the framework can be used to identify the number of neutralising antibodies. In addition, this model can explain why viruses might not completely loose their infection potential even when there is a huge excess of antibodies.

Date: 2013
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1002900

DOI: 10.1371/journal.pcbi.1002900

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