(600f) Design of an Optimal Temporal Immunization Strategy for Evolving Broadly Neutralizing Antibodies Against HIV

In 2016, an estimated 1.8 million people became infected with HIV, with 36.7 million people living with the virus worldwide [1], highlighting a clear and urgent need for a solution. The greatest challenge in developing a vaccine against HIV is undoubtedly accounting for and combating the highly mutable nature of HIV, thus an effective HIV vaccine will likely need to protect against many diverse "strains" or variants of the original infecting virus. Building off past work from the Chakraborty lab [2,3], this presentation will feature recent computational efforts to elicit antibodies (Abs) that can "broadly neutralize" a wide range of HIV variants, so-called "bNAbs". A coarse-grained computational model that is based in statistical mechanics, biological principles, and available experimental data has been developed to study the evolution of bNAbs through a biological process called “affinity maturation”. The effects on bNAb development of changing variables that are central to developing a successful vaccination strategy will be discussed in detail, such as the optimal number and concentration of immunogens to use, the relative sequence similarities of the immunogens, and the best way(s) in which to administer these immunogens in time. New, quantitative metrics that can be used to predict the quality of the produced Abs are described for the many different scenarios and parameters tested.

References

[1] “HIV/AIDS.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 18 Dec. 2017, www.cdc.gov/hiv/basics/statistics.html.

[2] Shaffer, J.S.; Moore, P.L; Kardar, M.; Chakraborty, A. Optimal Immunization Cocktails Can Promote Induction of Broadly Neutralizing Abs Against Highly Mutable Pathogens. PNAS 2016, 113, E7039-37048.

[3] Wang, S. et. al. Manipulating the Selection Forces during Affinity Maturation to Generate Cross-Reactive HIV Antibodies. Cell 2015, 160, 785-797.