Immunity to smallpox and vaccinia: the future of smallpox vaccines

Lane, John

doi:10.1586/1744666x.2.3.325

Cited by 5 publications

(2 citation statements)

References 20 publications

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“…Although the correlates of protective antipoxvirus immunity are still debated (reviewed in ref. 35), our results, along with others, suggest that, in response to a vaccinia infection, partial immunodeficiencies may be compensated for by any arm of the immune system. Immunodeficiencies may result in persistent infections, however, and we considered the possibility that the virus was not fully cleared after ST-246 treatment.…”

Section: Discussionsupporting

confidence: 82%

Efficacy of ST-246 versus lethal poxvirus challenge in immunodeficient mice

Grosenbach

Berhanu

King

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The threat of smallpox as a bioweapon and the emerging threat of human monkeypox, among other poxviral diseases, highlight the need for effective poxvirus countermeasures. ST-246, which targets the F13L protein in vaccinia virus and its homologs in other orthopoxvirus species, provides full protection from lethal poxviral disease in numerous animal models and seems to be safe in humans. All previous evaluations of ST-246 efficacy have been in immunocompetent animals. However, the risk of severe poxviral disease is greater in immunodeficient hosts. Here we report on the efficacy of ST-246 in preventing or treating lethal poxviral disease in immunodeficient mice. After lethal challenge with the Western Reserve strain of vaccinia, Nude, SCID, and J H knockout mice additionally depleted of CD4 + and CD8 + T cells were not fully protected by ST-246, although survival was significantly extended. However, CD4 + T cell deficient, CD8 + T cell deficient, J H knockout, and J H knockout mice also deficient for CD4 + or CD8 + T cells survived lethal challenge when treated with ST-246 starting on the day of challenge. Delaying treatment until 72 h after infection reduced ST-246 efficacy in some models but provided full protection from lethal challenge in most. These findings suggest that ST-246 may be effective in controlling smallpox or other pathogenic orthopoxviruses in some immunodeficient human populations for whom the vaccine is contraindicated.antiviral | immunodeficiency | ST-246 | smallpox | orthopoxvirus

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Section: Discussionsupporting

confidence: 82%

Efficacy of ST-246 versus lethal poxvirus challenge in immunodeficient mice

Grosenbach

Berhanu

King

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…CD8 + T cells protect against the disease, but CD4 + T cell dependent antibody production is indispensable in clearing the virus after acute infection. Moreover, CD4 + cells are more potent in the secretion of IFN-γ compared to CD4 + T cells ( 16 , 17 ). Vaccination is one of the best choices to trigger immune responses and neutralize invading pathogens.…”

Section: Introductionmentioning

confidence: 99%

Immunoinformatic-based design of immune-boosting multiepitope subunit vaccines against monkeypox virus and validation through molecular dynamics and immune simulation

et al. 2022

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Monkeypox virus is the causative agent of monkeypox disease, belonging to an orthopoxvirus genus, with a disease pattern similar to that of smallpox. The number of monkeypox cases have robustly increased recently in several countries around the world, potentially causing an international threat. Therefore, serious measures are indispensable to be taken to mitigate the spread of the disease and hence, under these circumstances, vaccination is the best choice to neutralize the monkeypox virus. In the current study, we used immunoinformatic approaches to target the L1R, B5R, and A33R proteins of the monkeypox virus to screen for immunogenic cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes to construct multiepitope subunit vaccines. Various online tools predicted the best epitope from immunogenic targets (L1R, B5R, and A33R) of monkeypox virus. The predicted epitopes were joined together by different linkers and subjected to 3D structure prediction. Molecular dynamics simulation analysis confirmed the proper folding of the modeled proteins. The strong binding of the constructed vaccines with human TLR-2 was verified by the molecular docking and determination of dissociation constant values. The GC content and codon adaptation index (CAI) values confirmed the high expression of the constructed vaccines in the pET-28a (+) expression vector. The immune response simulation data delineated that the injected vaccines robustly activated the immune system, triggering the production of high titers of IgG and IgM antibodies. In conclusion, this study provided a solid base of concept to develop dynamic and effective vaccines that contain several monkeypox virus-derived highly antigenic and nonallergenic peptides to control the current pandemic of monkeypox virus.

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