Live-attenuated CHIKV vaccine with rearranged genome replicates in vitro and induces immune response in mice.

Chikungunya fever virus (CHIKV) is a mosquito-borne alphavirus that causes wide-spread human infections and epidemics in Asia, Africa and recently, in the Americas. CHIKV is considered a priority pathogen by CEPI and WHO. Despite recent approval of a live-attenuated CHIKV vaccine, development of additional vaccines is warranted due to the worldwide outbreaks of CHIKV. Previously, we developed immunization DNA (iDNA) plasmid capable of launching live-attenuated CHIKV vaccine in vivo. Here we report the use of CHIKV iDNA plasmid to prepare a novel, live-attenuated CHIKV vaccine V5040 with rearranged RNA genome. In V5040, genomic RNA was rearranged to encode capsid gene downstream from the glycoprotein genes. Attenuated mutations derived from experimental CHIKV 181/25 vaccine were also engineered into E2 gene of V5040. The DNA copy of rearranged CHIKV genomic RNA with attenuated mutations was cloned into iDNA plasmid pMG5040 downstream from the CMV promoter. After transfection in vitro, pMG5040 launched replication of V5040 virus with rearranged genome and attenuating E2 mutations. Furthermore, V5040 virus was evaluated in experimental murine models for general safety and immunogenicity. Vaccination with V5040 virus subcutaneously resulted in elicitation of CHIKV-specific, virus-neutralizing antibodies. The results warrant further evaluation of V5040 virus with rearranged genome as a novel live-attenuated vaccine for CHIKV.

Land Ho! Polarized light serves as a visual signal for landward orientation in displaced spiders.

An organism's ability to identify goals within their environment, orient towards those goals, and successfully navigate to them are critical to all aspects of survival. Long-jawed orb weavers (Tetragnatha elongata) occupy riparian zones and perform orientation behaviors when displaced from this habitat onto the water. Spiders prefer to move toward the closest shoreline, regardless of release location, likely to avoid predation from fish. In this study, we conducted a series of investigations to determine the mechanism by which these spiders rapidly achieve zonal recovery. Occlusion experiments indicate that spiders use visual information to identify characteristics of the riparian habitat and navigate to shelter. While environmental characteristics such as color, contrast, and the sun's position do not appear to factor into this orientation behavior, the polarization of light appears critical. We propose that the polarization of light reflecting off the water's surface acts as a water detector and the absence of such at the edges of the pond (or via experimental induction) serves as a visual reference for the closest suitable habitat.

Orientation behavior of riparian long-jawed orb weavers (Tetragnatha elongata) after displacement over water.

Many organisms possess remarkable abilities to orient and navigate within their environment to achieve goals. We examined the orientation behavior of a riparian spider, the Long-Jawed Orb Weaver (Tetragnatha elongata), when displaced onto the surface of the water. When displaced, spiders move with alternating movements of the first three leg pairs while dragging the most posterior pair of legs behind them. In addition, spiders often perform a series of orientation behaviors consisting of concentric circles before ultimately choosing a path of travel directly toward the nearest point to land. While the number of orientation behaviors increased with increasing distance from shore, distance from shore had no effect on the direction of travel, which was significantly oriented toward the closest shoreline. These results indicate a complex ability to orient toward land when displaced onto water, possibly to decrease the amount of time on the surface of the water and thus decrease predation risk.