The presence of anti-YF nAb is a recognized hallmark of protection against YF infection. A dose of 104 PFUs of YF 17DD virus was potent enough to produce a high concentration of nAb after a single immunization in both mouse strains. The plasmid expressing the chimeric E-LAMP protein (pL/YFE) was able to produce significantly higher concentrations of anti-YF nAb after three immunizations in both mouse strains compared with the controls or p/YFE; however, the levels of nAb were considerably lower compared with the YF 17DD immunization. The p/YFE plasmid, expressing only the YF E protein, failed to generate high levels of anti-YF nAb in BALB/c mice and produced only a modest increase of anti-YF nAb in C57Bl/6 mice. These data are in accordance with previous reports demonstrating that the expression of chimeric proteins in-frame with LAMP lead to an improvement in B-cell responses [17, 22, 30]. Others have used extended immunization protocols to produce higher levels of antibody [17]. Although we have not tested this hypothesis here, it is interesting to speculate that extra DNA immunizations could further increase the levels of anti-YF nAb observed.