Immune responses elicited in rainbow trout through the administration of infectious pancreatic necrosis virus-like particles.

Virus like particles (VLPs) against viral pathogens not only constitute a novel approach for the development of antiviral vaccines for an specific virus, but also for the creation of multivalent vaccines in which antigens from other pathogens may be expressed on the surface of these VLPs. Despite positive results on protection for many of these VLPs in both fish and mammals, not many studies have focused on the immune response triggered by these particles; studies that may provide hints for the identification of immune mechanisms responsible for antiviral protection, which are mostly unknown in fish. In the current work, we have studied the levels of transcription of several immune genes in the spleen of rainbow trout (Oncorhynchus mykiss) intraperitoneally injected with VLPs from infectious pancreatic necrosis virus (IPNV) focusing on the chemokine response as well as the response of genes related to interferon (IFN) production. Surprisingly, the capacity of VLPs to induce chemokines differed from that of live IPNV, suggesting a direct effect of viral replication on the chemokine response in this organ. While VLPs up-regulated the transcription of CK3, CK10 and CXCd and down-modulated CK5B, CK6 and CK9 transcription, a previous study in which the transcription of γIP, CXCd, CK1, CK3, CK5B, CK6, CK7A, CK9 and CK12 had been studied demonstrated that IPNV only significantly up-regulated CK6 and down-modulated CK3 in the spleen. On the other hand, the administration of VLPs produced a strong mobilization to the peritoneum of CD4(+), IgM(+), IgT(+) and CD83(+) leukocytes similar to that induced by the live viral infection. In both cases, this leukocyte recruitment seemed to be greatly mediated through CK3, CK5B, CK9 and CK10 chemokine production. These results together with the fact that VLPs strongly induced non-specific lymphocyte proliferation and specific anti-IPNV antibody production point to VLPs as excellent candidates for vaccine development.

The introduction of multi-copy CpG motifs into an antiviral DNA vaccine strongly up-regulates its immunogenicity in fish.

The protection conferred by antiviral DNA vaccines in fish is known to rely greatly on innate immune responses. Since oligodeoxynucleotides (ODNs) containing unmethylated CpG dinucleotides (CpG motifs) have been shown to induce potential innate immune responses, we have introduced several copies (either two or four) of a fragment containing multiple CpG sequences of known immunostimulatory effects into a DNA vaccine against viral hemorrhagic septicemia virus (VHSV). We have determined the effects of this introduction on the vaccine immunogenicity, measured as immune gene induction, serum neutralizing activity and antigen-dependent proliferation. When comparing the effects of the vaccine containing 2 copies of this CpG fragment (pVHSV-2CpG) or that containing 4 copies of the fragment (pVHSV-4CpG) with the original VHSV DNA vaccine (pVHSV), we found that the levels of expression of type I interferon (IFN) were significantly up-regulated in muscle and spleen when the CpG fragments were introduced. An up-regulation in the levels of MHC-I expression in spleen were also observed in response to the modified vaccines, whereas, the levels of transcription of interleukin 1ß (IL-1ß) were strongly reduced in comparison to the original vaccine. Important but very variable differences were also observed concerning the vaccine induction of IFN-γ. Moreover, the serum neutralizing capacity was strongly increased as fish were vaccinated with plasmids containing more CpG fragments. Taken together, all these results demonstrate a strongly increased immunogenicity of the VHSV DNA vaccine, through the introduction of this multicopy CpG fragment.

A closer look at water-related geologic activity on Mars.

Water has supposedly marked the surface of Mars and produced characteristic landforms. To understand the history of water on Mars, we take a close look at key locations with the High-Resolution Imaging Science Experiment on board the Mars Reconnaissance Orbiter, reaching fine spatial scales of 25 to 32 centimeters per pixel. Boulders ranging up to approximately 2 meters in diameter are ubiquitous in the middle to high latitudes, which include deposits previously interpreted as finegrained ocean sediments or dusty snow. Bright gully deposits identify six locations with very recent activity, but these lie on steep (20 degrees to 35 degrees) slopes where dry mass wasting could occur. Thus, we cannot confirm the reality of ancient oceans or water in active gullies but do see evidence of fluvial modification of geologically recent mid-latitude gullies and equatorial impact craters.