The dosage of broadly neutralising antibodies determines the ability of the virus to replicate. Findings may help to design an HIV therapy that permanently suppresses the virus.
A research collaboration involving the University of Cologne, Germany has found a way to predict the effect of broadly neutralising antibodies (bNAbs) on the growth rate of HIV-1. The results are important for improving alternative immune-mediated therapies for HIV infections. The new findings are the result of a collaboration between scientists from the Institute of Biological Physics at the University of Cologne (Institut für Biologische Physik der Universität zu Köln) and the Institute of Virology at the University Hospital of Cologne (Institut für Virologie der Uniklinik Köln). The article “Predicting in vivo escape dynamics of HIV-1 from a broadly neutralizing antibody” has been published in the Proceedings of the National Academy of Sciences.
Great progress has already been made in controlling HIV infection. However, HIV-infected patients must adhere to a strict treatment regimen that includes taking a combination of drugs daily to suppress viral spread. HIV's extraordinary ability to evolve can further complicate treatment.
A new approach with the potential to improve treatment and prevention of HIV infection is broadly neutralising antibodies (bNAbs), which can recognise the virus and block its replication. However, the virus can make changes to its surface protein that allow it to evade recognition by the antibody.
bNAbs bind the surface protein of HIV, thereby preventing the virus from entering its target cells. However, if HIV evolves to evade antibodies, this advantage may come at a price. "Our hypothesis was that any variant that escapes detection will then replicate more slowly than the wild-type variant in an environment without antibodies. Reducing the growth rate of the so-called escape variant is the price of escape," says PhD student and first author Matthijs Meijers from Professor Michael Lässig's lab at the Institute of Biological Physics.
By analysing data from a clinical bNAb study conducted at the University Hospital of Cologne and Rockefeller University (New York, USA), the researchers found that there is indeed a trade-off between resistance to bNAbs on the one hand and reduced ability to replicate on the other. The escape variants observed in different individuals show remarkably similar behaviour: Their growth rate does not seem to depend significantly on the genomic background of the virus, which is different in each individual. Rather, it depends on two fitness factors: The antibody dose and the viral load. Therefore, the researchers were able to predict the escape dynamics of HIV-1 over the course of bNAb therapy.
Understanding how HIV escapes a bNAb can help design optimal treatment protocols. "Predicting the evolutionary response of the virus is a step towards controlling viral infection," says Professor Michael Lässig.
Predicting in vivo escape dynamics of HIV-1 from a broadly neutralising antibody Matthijs Meijers, Kanika Vanshylla, Henning Gruell, Florian Klein, Michael Lässig Proceedings of the National Academy of Sciences Jul 2021, 118 (30) e2104651118; DOI: 10.1073/pnas.2104651118