Development of NHP Models for Infectious Pathogens of Man

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For the cell tracking project, we have successfully developed the method we term serial intravascular staining to define the trafficking of cells over a 24 to 48 hour period In vivo. This technique has proven immensely useful for defining the relative trafficking rates of different subpopulations into and out of tissues. We are planning to marry this soon with labeled vaccines to define the trafficking rates of cells that initiate vaccine responses into a variety of tissues. For norovirus, we have begun the process of collecting norovirus strains from humans, and we'll mix them together in a single challenge to multiple nonhuman primates to try to find one or more strains that show at least some minimal replications in the primate gut. We've also successfully begun to grow nonhuman primate enteroids that shows the right morphology and cell composition. In collaboration with Dr Kwong at the VRC come on we will be using his NV probes to identify antigen specific B cells in both humans and in NHP, we from which we can generate novel monoclonal antibodies. Finally, for WEVEE, we have isolated almost 100 distinct nonhuman primate monoclonal antibodies two the three viruses; with our methodology, we can selectively identify those which are cross reactive to all three. We have shown that antibodies which bind all three viruses, will only neutralize one -- IE, neutralizing epitopes on the surface of these viruses are distinct. This suggests that Monoclonal antibody therapeutics or preventatives may require at least two distinct monoclonal antibodies for protection against all three viruses. In collaboration with Dr. Kwong at the VRC, we are crystalizing these monoclonal antibodies in context of each of the viral spikes in order to define the complete antigenic surface structure of the viruses and understand why they have distinct neutralizing epitopes.