Papers by Robert Johnston
Bookmarks Related papers MentionsView impact
Nature, 2003
Bookmarks Related papers MentionsView impact
The New England journal of medicine, Jan 19, 2004
Bookmarks Related papers MentionsView impact
Development (Cambridge, England), 2006
Bookmarks Related papers MentionsView impact
Current opinion in neurobiology, 2008
Bookmarks Related papers MentionsView impact
Cell, Jan 5, 2010
Bookmarks Related papers MentionsView impact
Annual review of cell and developmental biology, 2010
Bookmarks Related papers MentionsView impact
Vaccine, Jan 23, 2014
The eradication of poliovirus from the majority of the world has been achieved through the use of... more The eradication of poliovirus from the majority of the world has been achieved through the use of two vaccines: the inactivated poliovirus vaccine (IPV) and the live-attenuated oral poliovirus vaccine (OPV). Both vaccines are effective at preventing paralytic poliomyelitis, however, they also have significant differences. Most importantly for this work is the risk of revertant virus from OPV, the greater cost of IPV, and the low mucosal immunity induced by IPV. We and others have previously described the use of an alphavirus-based adjuvant that can induce a mucosal immune response to a co-administered antigen even when delivered at a non-mucosal site. In this report, we describe the use of an alphavirus-based adjuvant (GVI3000) with IPV. The IPV-GVI3000 vaccine significantly increased systemic IgG, mucosal IgG and mucosal IgA antibody responses to all three poliovirus serotypes in mice even when administered intramuscularly. Furthermore, GVI3000 significantly increased the potency of IPV in rat potency tests as measured by poliovirus neutralizing antibodies in serum. Thus, an IPV-GVI3000 vaccine would reduce the dose of IPV needed and provide significantly improved mucosal immunity. This vaccine could be an effective tool to use in the poliovirus eradication campaign without risking the re-introduction of revertant poliovirus derived from OPV.
Bookmarks Related papers MentionsView impact
Science (New York, N.Y.), Jan 7, 2014
Bookmarks Related papers MentionsView impact
Vaccine, Jan 7, 2014
Bookmarks Related papers MentionsView impact
Journal of virology, 2014
Neonatal immune responses to infection and vaccination are biased toward TH2 at the cost of proin... more Neonatal immune responses to infection and vaccination are biased toward TH2 at the cost of proinflammatory TH1 responses needed to combat intracellular pathogens. However, upon appropriate stimulation, the neonatal immune system can induce adult-like TH1 responses. Here we report that a new class of vaccine adjuvant is especially well suited to enhance early life immunity. The GVI3000 adjuvant is a safe, nonpropagating, truncated derivative of Venezuelan equine encephalitis virus that targets dendritic cells (DCs) in the draining lymph node (DLN) and produces intracellular viral RNA without propagating to other cells. RNA synthesis strongly activates the innate immune response so that in adult animals, codelivery of soluble protein antigens induces robust humoral, cellular, and mucosal responses. The adjuvant properties of GVI3000 were tested in a neonatal BALB/c mouse model using inactivated influenza virus (iFlu). After a single immunization, mice immunized with iFlu with the GVI3000 adjuvant (GVI3000-adjuvanted iFlu) had significantly higher and sustained influenza virus-specific IgG antibodies, mainly IgG2a (TH1), compared to the mice immunized with antigen only. GVI3000 significantly increased antigen-specific CD4(+) and CD8(+) T cells, primed mucosal immune responses, and enhanced protection from lethal challenge. As seen in adult mice, the GVI3000 adjuvant increased the DC population in the DLNs, caused activation and maturation of DCs, and induced proinflammatory cytokines and chemokines in the DLNs soon after immunization, including gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), granulocyte colony-stimulating factor (G-CSF), and interleukin 6 (IL-6). In summary, the GVI3000 adjuvant induced an adult-like adjuvant effect with an influenza vaccine and has the potential to improve the immunogenicity and protective efficacy of new and existing neonatal vaccines. The suboptimal immune responses in early life constitute a significant challenge for vaccine design. Here we report that a new class of adjuvant is safe and effective for early life immunization and demonstrate its ability to significantly improve the protective efficacy of an inactivated influenza virus vaccine in a neonatal mouse model. The GVI3000 adjuvant delivers a truncated, self-replicating viral RNA into dendritic cells in the draining lymph node. Intracellular RNA replication activates a strong innate immune response that significantly enhances adaptive antibody and cellular immune responses to codelivered antigens. A significant increase in protection results from a single immunization. Importantly, this adjuvant also primed a mucosal IgA response, which is likely to be critical for protection during many early life infections.
Bookmarks Related papers MentionsView impact
PloS one, 2015
Bookmarks Related papers MentionsView impact
Managing Service Quality, 2011
Home > Managing Service Quality > Volume 21 issue 1 > The customer experience: a road-ma... more Home > Managing Service Quality > Volume 21 issue 1 > The customer experience: a road-map for... ... Icon: Abstract. Icon: Backfiles. Icon: Print. Icon: Reprints & permissions. ... The authors are indebted to Professor Scott Sampson from Brigham Young University for his ...
Bookmarks Related papers MentionsView impact
Choice experiments are designed to account for variations in environmental resources and site cha... more Choice experiments are designed to account for variations in environmental resources and site characteristics, as well as potential implications of these variations for willingness to pay. This may render choice experiment results highly suitable for benefits transfer. It is unclear, however, whether the flexibility of choice experiments renders the similarity of study and transfer sites less critical for transfer validity.
Bookmarks Related papers MentionsView impact
Virology, 1995
Venezuelan equine encephalitis virus (VEE) causes a biphasic disease in mice following subcutaneo... more Venezuelan equine encephalitis virus (VEE) causes a biphasic disease in mice following subcutaneous inoculation in the footpad. In the initial phase, virus replicates primarily in the lymphoid tissues and induces a high titer viremia. Subsequently, the virus invades the central nervous system (CNS) from the circulation, and an encephalitis ensues. At the earliest times that VEE specific in situ hybridization signal was observed in the CNS, it was in areas of the brain involved in olfaction, leading to the hypothesis that virus may invade the brain from the circulation through the olfactory system. The results presented in this paper define the route of CNS invasion in experimental murine VEE disease initiated by subcutaneous inoculation. Virus circulating in the blood appears to seed specific areas of the peripheral nervous system during the viremic lymphoid phase of the illness. Virus replication within olfactory and dental tissues is followed by centripetal spread of virus along neural pathways. Virus enters the brain in a pattern reflecting the proximity of the peripheral invasion site to the CNS. Specifically, virus is first found in the brain within the structures of the olfactory system, followed by areas innervated by the trigeminal nerve. Virus later disseminates along fiber tracts and connected circuits within the brain, resulting in a disseminated meningoencephalitis. Surgical or chemical interruption of the olfactory system at the level of the olfactory neuroepithelium or the main olfactory bulb inhibited entry of VEE into the CNS through the olfactory nerve. However, the olfactory route is not absolutely required for CNS invasion, as virus invaded the CNS of olfactory ablated animals through the trigeminal nerve. These observations are consistent with a model of hematogenous seeding of the peripheral nervous system, followed by invasion of the CNS by direct neural spread.
Bookmarks Related papers MentionsView impact
Environmental Management and Health, 1996
Few environmental problems can be contained to one defined segment of the earth’s surface; becaus... more Few environmental problems can be contained to one defined segment of the earth’s surface; because of the inter-connectedness of environmental systems, most problems spill over into other areas. A logical consequence is that environmental problems can only be tackled vigorously at the global scale. But human organization of the earth’s surface has divided it into a large number of territorial
Bookmarks Related papers MentionsView impact
... Analysts conducting primary nonmarket valuation research may choose among several established... more ... Analysts conducting primary nonmarket valuation research may choose among several established and ... theory suggests that welfare estimates for otherwise identical resource improvements should ... a broader lack of consensus over whether the common meta-analytic finding ...
Bookmarks Related papers MentionsView impact
PLOS Medicine, 2006
Bookmarks Related papers MentionsView impact
Immunity, Jan 21, 2014
Bookmarks Related papers MentionsView impact
Journal of Comparative Psychology, 2008
In humans, individuals recognize other individuals by numerous types of independent information, ... more In humans, individuals recognize other individuals by numerous types of independent information, such as the quality of the voice, appearance of the face, smell, gait, and posture. Humans also have integrated memories of others--that is, in response to a face or a voice the individual is recognized by name and other information about that individual is remembered. In many nonhuman species, individual recognition also occurs. Although observational studies suggest that individuals of some nonhuman species may be able to use several different cues for individual recognition, little experimental proof for this is available. Golden hamsters have at least 5 individually distinctive odors and they develop integrated, multi-odor memories (concepts) of familiar individuals, as shown by across-odor habituation experiments. Little is known, however, about the conditions that are necessary to develop such integrated memories. In these experiments we investigated what kinds of experiences were necessary for male hamsters to develop multiodor memories of females. The results show that exposure to all of the odors of another individual was not sufficient to develop such multiodor memories but that physical contact between the subjects and stimulus animals was necessary. Multiodor representations were developed after interactions with anesthetized individuals, confirming the finding that physical contact was important but also showing that interaction with an awake, behaving individual was not necessary to form multiodor representations of other individuals. We are not aware of experimental proof for integrated, multicomponant memories in any other nonhuman species.
Bookmarks Related papers MentionsView impact
Uploads
Papers by Robert Johnston