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, 2014), we suspect that animals succumbing beyond 7 days post-RVFV challenge had very high viral loads in the brain and associated neurologic disease. FIGURE 2 Survival of hamsters Selleckchem GSK-J4 challenged s.c. with RVFV that received post-exposure treatment with rMP12-C13type or MP-12 vaccine strains. Animals in each group (n = 10) were treated s.c. with 1 �� 105 PFU of rMP12-C13type, MP-12 or placebo at 8, 12, or ... The effect of the post-exposure treatments on reducing viral titers in subsets of animals sacrificed on day 2 post-infection is shown in Figure ?Figure3.3. Treatment with rMP12-C13type significantly reduced day 2 viral titers at all three timepoints in serum and tissues compared to the MP-12 treatment at 8 hpi. The decrease in viral loads correlated with the time of rMP12-C13type treatment with the 8 hpi group having undetectable levels of virus in most cases and less dramatic reductions observed in the 24 hpi group. Notably, one animal from the MP-12 treatment group and two from the placebo group succumbed prior to sacrifice on day 2, further demonstrating the severity of disease in animals that did not receive rMP12-C13type post-exposure vaccine treatment. FIGURE 3 Analysis of serum and tissue viral titers in RVFV-infected hamsters treated with rMP12-C13type or MP-12 vaccine strains. Hamsters were treated as described in Figure ?Figure22 and up to four animals in each group were sacrificed on day 2 post-infection ... Efficacy of Post-exposure Vaccination with rMP12-C13type in Hamsters Challenged i.n. with RVFV Exposure to RVFV can also occur through the respiratory tract. Therefore, we also investigated the use of rMP12-C13type treatment in this capacity. In this study, a recombinant MP-12 virus (rMP-12) served as the comparison control for the rMP12-C13type vaccine, and along with the PBS placebo, all were administered by s.c. injection at 6 or 24 hpi with i.n. RVFV ZH501 to model respiratory tract exposure. As shown in Figure ?Figure4,4, only a weak protective effect based on extended survival time was observed in the i.n. challenge model in animals treated with rMP12-C13type within 6 hpi. There was no effect of rMP12-C13type treatment when administered 24 hpi (Figure ?(Figure4).4). Considering the highly effective post-exposure vaccination observed in the s.c. challenge model, and the fact that rMP12-C13type treatment was more efficacious in the mouse i.n. infection model (Gowen et al., 2013), the results were unexpected. FIGURE 4 Effect of post-exposure treatment with rMP12-C13type or rMP-12 vaccine strains on survival outcome in hamsters challenged i.n. with RVFV. Animals in each group (n = 10) were treated s.c. with 1 �� 105 PFU of rMP12-C13type or MP-12 at (A) 6 h or ...