Highly pathogenic alphaviruses like VEEV/EEV/WWEEV cause encephalitis in humans and equids. These infections are endemic in wide regions of the developing world. Translational research regarding these pathogens is focused on developing new strategies to detect, treat and ideally protect humans and animals from these infections. Gene-encoded antibodies against alphavirus E1/E2 surface proteins will be developed and evaluated, in this Phase I SBIR project, as therapeutic molecules. The intent of these studies is to create new antibody-based prophylactics that can neutralize VEEV infections. As a first step, we develop novel antibody fragments that bind specifically to their cognate antigen on surface of VEEV. We will also assess the relative performance and compatibility of delivery strategies for introduction of the antibody fragments across the blood brain barrier. These optimized formulations will be assessed for therapeutic benefit in future challenge studies.