The 1918 influenza pandemic was unusually severe, resulting in about 50 million deaths worldwide. The 1918 virus is also highly pathogenic in mice, and studies have identified a multigenic origin of this virulent phenotype in mice. However, these initial characterizations of the 1918 virus did not address the question of its pathogenic potential in primates. Here we demonstrate that the 1918 virus caused a highly pathogenic respiratory infection in a cynomolgus macaque model that culminated in acute respiratory distress and a fatal outcome. Furthermore, infected animals mounted an immune response, characterized by dysregulation of the antiviral response, that was insufficient for protection, indicating that atypical host innate immune responses may contribute to lethality. The ability of influenza viruses to modulate host immune responses, such as that demonstrated for the avian H5N1 influenza viruses, may be a feature shared by the virulent influenza viruses.

Vaccines and therapies are urgently needed to address public health needs stemming from emerging pathogens and biological threat agents such as the filoviruses Ebola virus (EBOV) and Marburg virus (MARV). Ebola virus (EBOV) and Marburg virus (MARV) of the virus familyFiloviridae are emerging and reemerging pathogens that cause hemorrhagic fever with high mortality rates in humans and nonhuman primates 1-3 . The public health concern about filoviruses has increased in recent years as a result of increased awareness and frequency of cases in central Africa as evidenced by the current outbreak of MARV in Angola 4 and also because filoviruses are considered to be potential agents of bioterrorism 5 . Currently, there are no EBOV or MARV vaccines or therapies approved for human use. Recently, we generated live attenuated recombinant vesicular stomatitis viruses (rVSV) expressing the transmembrane glycoprotein of Zaire ebolavirus (ZEBOV; VSV ∴∆G/ZEBOVGP) and MARV (VSV∆G/MARVGP) 6 . Our study evaluated the utility of these rVSV vectors as candidate vaccines for EBOV and MARV using the cynomolgus macaque model.Filovirus vaccine research has been extensively reviewed in the past and has primarily focused on EBOV 7,8 . The first EBOV vaccine to protect nonhuman primates was a DNA prime-adenovirus boost approach using both the glycoprotein and nucleoprotein as target antigens 9 . This approach required several months for immunity to develop, which limited the utility of this strategy. More recently, an accelerated vaccine was described. A single immunization of nonhuman primates with 2 × 10 12 particles of an equal mixture of human adenovirus 5 vectors carrying either the gene encoding ZEBOV glycoprotein or the gene encoding ZEBOV nucleoprotein resulted in complete protection against ZEBOV 10 . Despite the intriguing success of the adenovirus vaccine, preexisting immunity rates of between 40 and 60% have been reported to adenovirus in the human population and this may eventually limit the utility of this approach [11][12][13] .A smaller number of efforts have focused on developing vaccines against MARV. Alphavirus replicons expressing MARV proteins protected cynomolgus monkeys from homologous MARV challenge 14 . Subsequent studies evaluating this platform as a vaccine for EBOV were less encouraging, as the EBOV counterpart of this alphavirus replicon platform was unable to protect any animal against lethal EBOV challenge under similar test conditions 7 . The ideal vaccine would protect humans from infection from all four EBOV species (ZEBOV, Sudan ebolavirus (SEBOV), Reston ebolavirus, Ivory Coast ebolavirus) and MARV. Although the adenovirusbased vaccine platform has completely protected nonhuman primates against ZEBOV 9,10 , and the platform based on alphavirus replicons protected monkeys against MARV 14 , no platform has demonstrably protected nonhuman primates against both of these viruses.Vaccines based on live attenuated rVSV have been highly effective in animal models and are particularly attractive because they can ...

The Stardust spacecraft collected thousands of particles from comet 81P/Wild 2 and returned them to Earth for laboratory study. The preliminary examination of these samples shows that the nonvolatile portion of the comet is an unequilibrated assortment of materials that have both presolar and solar system origin. The comet contains an abundance of silicate grains that are much larger than predictions of interstellar grain models, and many of these are high-temperature minerals that appear to have formed in the inner regions of the solar nebula. Their presence in a comet proves that the formation of the solar system included mixing on the grandest scales.