Narendra M. Dixit's Talk

Aug 10, 2018 - 16:00

Aug 10, 2018 - 17:00

Room 230 Chemical Engg Dept

Seminars

Narendra M. Dixit Department of Chemical Engineering Indian Institute of Science Bangalore

The design of a potent vaccine for HIV has been challenging because of the massive genomic diversity of the virus in infected individuals. Some rare individuals naturally elicit antibodies that can neutralize this diverse collection of viruses. These antibodies are called broadly neutralizing antibodies (bNAbs). The individuals however elicit them late 2 or more years into the infection and in quantities that are too low to cure the infection. Enormous efforts are underway to expedite the production of bNAbs and to enhance their levels in the blood in all infected individuals. In a recent breakthrough administration of externally generated bNAbs to infected individuals was found to hugely improve their production internally. Further this effect lasted long after the administered bNAbs were cleared from circulation. This breakthrough raises hopes of engineering potent vaccines for HIV. The mechanism underlying the observed clinical effect however is unknown precluding rational optimization of such vaccine strategies. Antibodies are produced in temporary structures called germinal centers in the body. Here focussed Darwinian evolution occurs where cells that can produce antibodies of high affinity for the pathogen are preferentially selected. Administered antibodies can skew this selection. We constructed detailed stochastic simulations of this evolutionary process based on a mechanistic hypothesis we proposed of the role of administered antibodies. The simulations explained the recent clinical breakthrough and several other confounding observations. Further they unravelled a quality-quantity trade-off that limits the evolution in the germinal centers. Using the simulations we identified vaccination protocols that could exploit this trade-off and enhance the speed and the quantity of the production of bNAbs