Investigator, Asst Prof (M) Ragon PIs 1, Mass General Research Institute

Assistant Professor of Medicine Harvard Medical School

aids vaccines; antibodies neutralizing; dependovirus; gene transfer techniques; genetic vectors; hiv; hiv antibodies; hiv immunity; host-pathogen interactions; immune-mediated viral evolution; immunization; immunization passive; innate immunity; orthogonal antibody neutralization

The Nature of Sterilizing Immunity

The ultimate goal of any prophylactic intervention is the induction of immunity so overwhelming that the targeted pathogen has no opportunity to establish an infection in the host. One of my major interests is in understanding this process to engineer this level of immunity against HIV.

Pathogen Escape from Immunological Pressure

As host and pathogen come together, a complex immunological interaction ultimately determines the victor. Successful pathogens are capable of avoiding the immune system through evolution to escape host immunity. I am interested in studying this process at its most fundamental level.

The Role of Innate Immunity in Neutralization

Innate immunological responses have been found to play an important role in preventing infection, but the involvement of innate immunity in generating sterilizing protection in vivo has not been characterized. I seek to understand the contribution of innate immunity to this process.

Orthogonal Antibody Neutralization

When a pathogen is neutralized by a given monoclonal antibody, there is a natural selection towards variants that are no longer recognized. In a polyclonal response, multiple selective pressures are applied to a pathogen in concert. If this pressure occurs more quickly than the ability of a pathogen to evolve, it may be feasible to create a "checkmate" scenario that prevents escape. I am interested in applying this concept to ongoing HIV replication with existing neutralizing antibodies.

Immune-mediated Viral Evolution In Vivo

When a single virus initiates an infection, it rapidly proliferates to become a diverse population known as a quasispecies. This swarm of viral genotypes is what enables the evolution of resistance to diverse selective pressures. We hope to understand the genetic changes occuring in this quasispecies as a result of immunological selective pressure with the goal of predicting viral evolution and preventing immunological escape.