Autonomous Targeting of Infectious Superspreaders Using Engineered Transmissible Therapies

Metzger, Vincent T.; Lloyd-Smith, James O.; Weinberger, Leor S.

We introduce a proposed intervention against infectious diseases that extends and optimizes the recognized benefit of 'transmissible immunization' that occurs with live-attenuated vaccines such as Oral Polio Vaccine (OPV), the vaccine chosen for the worldwide polio eradication campaign. The intervention proposed here is based upon Therapeutic Interfering Particles (TIPs) that are engineered to replicate only in the presence of the wildtype pathogen and act to inhibit the growth of the pathogen. Therefore TIPs 'piggyback' on the pathogen, leading to two important differences from live-attenuated vaccines: TIPs can only transmit from individuals already infected with wildtype pathogen, and TIPs could only revert to virulence in individuals already carrying the wild-type pathogen. Intriguingly, because TIPs spread between individuals using the same transmission routes as the pathogen, they automatically find their way to the populations at greatest risk of infection, thus circumventing the unsolved problem of how to identify superspreaders and target them for preventive measures. Based on clinical-trial data, we analyze the impact that TIP intervention would have on HIV/AIDS in sub-Saharan Africa and show that TIPs could lower HIV/AIDS prevalence more effectively than vaccines or drugs alone and, in fact, would effectively complement these other interventions.