Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters. PLoS Pathogens
Brandenberg et al. experimentally determined molecular parameters of the HIV-1 envelope trimer – broadly neutralizing antibody interaction, and subsequently devised a mathematical model of HIV-1 infection and antibody neutralization in vivo. The reason for this work was that the potential of broadly neutralizing antibodies targeting the HIV-1 envelope trimer to prevent HIV-1 transmission has opened new avenues for therapies and vaccines. However, their implementation remains challenging and would profit from a deepened mechanistic understanding of HIV-antibody interactions and the mucosal transmission process.
The authors experimentally confirmed that binding of one antibody per HIV-1 envelope trimer is sufficient for trimer neutralization. This finding defines numerical requirements for HIV-1 virion neutralization and thereby enables mathematical modelling of in vitro and in vivo antibody neutralization efficacy.
In a next step, they employed the model for a post-hoc analysis of non-human primate infection studies, thereby obtaining estimates of HIV-1 neutralization in vivo and the probability for a single HIV-1 virion to initiate host infection. They found that the per-act likelihood of female HIV-1 infection is clearly driven by the size of the virus inoculum and retrieved per-act virus transmission probabilities in good agreement with empirical estimates. Furthermore, the model provided estimates for mucosal neutralizing antibody (nAb) concentrations required to provide protection from infection, indicating that nAb concentrations in the low μg/ml range may provide protection from mucosal HIV-1 transmission.
In conclusion, the combined experimental-mathematical approach delivers precise estimates of virion-antibody interaction stoichiometry, single-virion mucosal transmission probability, male to female per-act infection risk and in vivo nAb neutralization efficacy. These data represent novel quantitative insights into both the molecular details of HIV-1 antibody neutralization and the systemic level of mucosal HIV-1 infection.