Abstract
Experimental studies have shown that the size and infectious-stage of viral inoculum influence disease outcomes in rhesus macaques infected with simian immunodeficiency virus. The possible contribution to disease outcome of antibody developed after transmission and/or present in the inoculum in free or bound form is not understood. In this study, we develop a mathematical model of virus-antibody immune complex formation and use it to predict their role in transmission and protection. The model exhibits a bistable switch between clearance and persistence states. We fitted it to temporal virus data and estimated the parameter values for free virus infectivity rate and antibody carrying capacity for which the model transitions between virus clearance and persistence when the initial conditions (in particular the ratio of immune complexes to free virus) vary. We used these results to quantify the minimum virus amount in the inoculum needed to establish persistent infections in the presence and absence of protective antibodies.
Highlights
The humoral immune response is one of the first barriers against infecting pathogens and forms the basis for most vaccines that are currently in use (Plotkin, 2008; Deal and Balazs, 2015)
Animal models have proven useful in examining the mechanisms of virus-antibody interactions that lead to protection against human immunodeficiency virus (HIV) infections
We develop a mathematical model of antibody-virus dynamics that assumes interaction between virus, recipient and donor antibody, and the corresponding immune complexes
Summary
The humoral immune response is one of the first barriers against infecting pathogens and forms the basis for most vaccines that are currently in use (Plotkin, 2008; Deal and Balazs, 2015). The rapidly mutating human immunodeficiency virus (HIV), evades humoral immune responses in most human infections due to difficulties in eliciting neutralizing antibodies that are effective against the enormous diversity of virus strains (Haynes, 2015). Studies using the chimeric simian-human rhesus macaque model (SHIV) have shown that passive transfer of broadly neutralizing monoclonal antibodies (bnMAbs) can induce protection against mucosal challenge (Moldt et al, 2012). The potential for inducing neutralizing antibodies that correlate with protection in vivo has been shown during simian immunodeficiency virus (SIV) infections of ENVvaccinated rhesus macaques (Letvin et al, 2011), suggesting that it may be possible to elicit antibody-mediated protection through vaccination. Understanding the properties of antibodies, such as concentration and avidity needed for protection based on known virus count in the inoculum, is important information that can guide vaccine design
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