Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2007 Mar 30;360(1):36-49.
doi: 10.1016/j.virol.2006.10.026. Epub 2006 Nov 13.

Neurovirulence properties of recombinant vesicular stomatitis virus vectors in non-human primates

J Erik Johnson  1 , Farooq Nasar, John W Coleman, Roger E Price, Ali Javadian, Kenneth Draper, Margaret Lee, Patricia A Reilly, David K Clarke, R Michael Hendry, Stephen A Udem
Affiliations
Comparative Study

Neurovirulence properties of recombinant vesicular stomatitis virus vectors in non-human primates

J Erik Johnson et al. Virology. .

Abstract

Although vesicular stomatitis virus (VSV) neurovirulence and pathogenicity in rodents have been well studied, little is known about VSV pathogenicity in non-human primates. To address this question, we measured VSV viremia, shedding, and neurovirulence in macaques. Following intranasal inoculation, macaques shed minimal recombinant VSV (rVSV) in nasal washes for 1 day post-inoculation; viremia was not detected. Following intranasal inoculation of macaques, wild type (wt) VSV, rVSV, and two rVSV-HIV vectors showed no evidence of spread to CNS tissues. However, macaques inoculated intrathalamically with wt VSV developed severe neurological disease. One of four macaques receiving rVSV developed clinical and histological signs similar to the wt group, while the remaining three macaques in this group and all of the macaques in the rVSV-HIV vector groups showed no clinical signs of disease and reduced severity of histopathology compared to the wt group. The implications of these findings for rVSV vaccine development are discussed.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
NHP safety study designs. (A) Rhesus macaque shedding study. The genome organization of the rVSVIN virus is depicted, and the dose, route of inoculation, and controls for the study are indicated. (B) Cynomolgus macaque NV and neuroinvasiveness studies. The genome organization of each virus or vector is depicted, along with the dose per macaque, route of inoculation, the number of macaques per group, and the day of scheduled euthanasia. (C) Bars indicate sections of cynomolgus macaque brain tissue and spinal cord sections collected at necropsy for histological analysis in the NV and neuroinvasiveness studies. Anatomical regions covered by collected sections are also indicated.
Fig. 2
Fig. 2
Brain histology. Photomicrographs of hematoxylin and eosin stained sections of lateral ventricle from the thalamic region of the brain of cynomolgus macaques following IT inoculation of: (A) wt VSVIN (macaque number 22212M) with severe periventricular inflammation and malacia, severe choroiditis, and loss of ependymal cells; (B) rVSVIN (macaque number 21789F) with moderate periventricular inflammation; (C) rVSVIN-HIVGag5 (macaque number 22245M) with moderate periventricular inflammation; (D) rVSVIN-CT1-HIVGag5 (macaque number 21797F) with minimal periventricular inflammation; (E) PBS (macaque number 22238M) with no significant lesions observed; (F) rVSVIN-CT1-HIVGag5 (macaque number 21797F, higher magnification), showing characteristic mononuclear inflammatory cell infiltrate composed primarily of lymphocytes, plasma cells, and mononuclear phagocytes along with scattered eosinophils. Black arrow = ependyma, red arrow = denuded ependyma, black arrow head = perivascular cuffs, red arrow head = eosinophil, M = malacia, and CP = choroids plexus. Magnification: A–E = 100 × and F = 400 ×.
Fig. 3
Fig. 3
Spinal cord histology. Photomicrographs of hematoxylin and eosin stained sections of lumbar spinal cord of cynomolgus macaques following IT inoculation of: (A) wt VSVIN (macaque number 22212M) with moderate multifocal gliosis, microhemorrhages, and mononuclear perivascular cuffs; (B) rVSVIN (macaque number 21789F) with severe multifocal coalescing gliosis and malacia, and prominent mononuclear perivascular cuffs; (C) rVSVIN-HIVGag5 (macaque number 21578F) with marked multifocal coalescing gliosis and malacia and prominent mononuclear perivascular cuffs; (D) rVSVIN-CT1-HIVGag5 (macaque number 21576F) with minimal focal gliosis; (E) PBS (macaque number 21724M) with no significant lesions observed; (F) rVSVIN-CT1-HIVGag5 (macaque number 21789F, higher magnification), showing characteristic mononuclear perivascular inflammatory cell infiltrate composed primarily of lymphocytes, plasma cells, and mononuclear phagocytes. Panels A–E: black arrow = gliosis, black arrowhead = mononuclear perivascular cuffs, white arrow = neurons, W = white matter, G = gray matter, O = central canal of spinal cord. Panel F: Black arrow = macrophage, black arrowhead = plasma cell, white arrow = endothelial cell, and white arrowhead = lymphocyte. Magnification: A–E = 100 × and F = 400 ×.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Arya S.C. Yellow fever vaccine safety: a reality or a myth? Vaccine. 2002;20(31–32):3627–3628. - PubMed
    1. Ball L.A., Pringle C.R., Flanagan B., Perepelitsa V.P., Wertz G.W. Phenotypic consequences of rearranging the P, M, and G genes of vesicular stomatitis virus. J. Virol. 1999;73(6):4705–4712. - PMC - PubMed
    1. Bi Z., Barna M., Komatsu T., Reiss C.S. Vesicular stomatitis virus infection of the central nervous system activates both innate and acquired immunity. J. Virol. 1995;69(10):6466–6472. - PMC - PubMed
    1. Brandly C.A., Hanson R.P. Epizootiology of vesicular stomatitis. Am. J. Public Health. 1957;47(2):205–209. - PMC - PubMed
    1. Brody J.A., Fischer G.F., Peralta P.H. Vesicular stomatitis virus in Panama. Human serologic patterns in a cattle raising area. Am. J. Epidemiol. 1967;86(1):158–161. - PubMed

Publication types

MeSH terms