Smallpox, “the most dreadful scourge of the human species”

Fenner, Frank

doi:10.5694/j.1326-5377.1984.tb132965.x

Cited by 10 publications

(6 citation statements)

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“…VARV is the causative agent of human smallpox with mortality rates of 10–30%. Although smallpox was declared eradicated in 1980 following a global immunization campaign [ 1 ], monkeypox, a zoonotic disease, is emerging as a significant threat globally [ 2 ]. Monkeypox Zaire or Clade I, causes a human disease similar to smallpox with a mortality rate of 10%.…”

Section: Introductionmentioning

confidence: 99%

Single Dose of Recombinant Chimeric Horsepox Virus (TNX-801) Vaccination Protects Macaques from Lethal Monkeypox Challenge

Noyce

Westfall

Fogarty

et al. 2023

Viruses

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The ongoing global Monkeypox outbreak that started in the spring of 2022 has reinforced the importance of protecting the population using live virus vaccines based on the vaccinia virus (VACV). Smallpox also remains a biothreat and although some U.S. military personnel are immunized with VACV, safety concerns limit its use in other vulnerable groups. Consequently, there is a need for an effective and safer, single dose, live replicating vaccine against both viruses. One potential approach is to use the horsepox virus (HPXV) as a vaccine. Contemporary VACV shares a common ancestor with HPXV, which from the time of Edward Jenner and through the 19th century, was extensively used to vaccinate against smallpox. However, it is unknown if early HPXV-based vaccines exhibited different safety and efficacy profiles compared to modern VACV. A deeper understanding of HPXV as a vaccine platform may allow the construction of safer and more effective vaccines against the poxvirus family. In a proof-of-concept study, we vaccinated cynomolgus macaques with TNX-801, a recombinant chimeric horsepox virus (rcHPXV), and showed that the vaccine elicited protective immune responses against a lethal challenge with monkeypox virus (MPXV), strain Zaire. The vaccine was well tolerated and protected animals from the development of lesions and severe disease. These encouraging data support the further development of TNX-801.

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Section: Introductionmentioning

confidence: 99%

Single Dose of Recombinant Chimeric Horsepox Virus (TNX-801) Vaccination Protects Macaques from Lethal Monkeypox Challenge

Noyce

Westfall

Fogarty

et al. 2023

Viruses

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“…Over the past few years, the potential risks for the possible release of lethal viruses by bioterrorists have stimulated the development of new therapies against poxviruses. Smallpox, which was considered one of the most devastating human diseases in history, was definitely eradicated in the late 1970s following a mass vaccination campaign [1]. The causative agent of smallpox is the orthopoxvirus variola virus (VARV).…”

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confidence: 99%

Specific Targeting of the F13L Protein by St-246 Affects Orthopoxvirus Production Differently

et al. 2008

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Background ST-246 is a potent anti-orthopoxviral molecule targeting the F13L protein of vaccinia virus, which is involved in the wrapping of viruses. The discrepancy in sensitivities of several orthopoxviruses to ST-246 has raised questions about potential differences in their replicative cycles and/or the presence of another drug target. Methods Density gradients were used to evaluate the differences between the viral cycles of vaccinia, cow-pox and camelpox viruses. Also, to investigate if ST-246 inhibits a single target, we compared its activity to that of small interfering RNAs designed to silence the F13L gene (siF13Ls). Results We showed that the spread of vaccinia virus involved both intracellular and extracellular enveloped viruses, whereas both cowpox and camelpox viruses seemed to propagate via non-enveloped intracellular forms and cell-associated viral particles. Although ST-246 exerted a clear antiviral activity by interfering with the egress of the virus from infected cells, we observed that cowpox and camelpox viruses, in contrast to vaccinia virus, could be directed towards a lytic cycle under ST-246 treatment. We specifically knocked down the F13L transcripts of vaccinia and camelpox viruses by >85%, reduced virus progeny by 90% and showed that siF13Ls affect camelpox and vaccinia virus propagation differently. Flow cytometry data validated that ST-246 interfered with the activity of the F13L protein, whereas siF13Ls silenced the F13L gene. Conclusions Our observations support that vaccinia, cow-pox and camelpox viruses exhibit different levels of sensitivity to ST-246 because of dissimilarities between their ways of propagation, and provide a better understanding of the mode of action of ST-246.

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“…He stated that ‘he also heard a most lugubrious dirge chaunted at a Corrobera at Bathurst, commemorative of this destructive epidemic, and judged accurately of its nature from the melancholy note and solemn manner of the pageant.’ It was found in the natives by Major Mitchell after crossing the Liverpool Range in 1831. The disease may possibly have spread extensively into Queensland 10–13 …”

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confidence: 99%

“…As in the 1789 outbreak, the source(s) of the outbreak were never determined. Various possibilities have been discussed by Fenner 13 …”

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confidence: 99%

“…Altogether, 12 people contracted smallpox. During the 1860s and 1870s, smallpox had been active in the Top End of the Northern Territory and farther south to Tennant Creek and the Finke River, where pock‐marked natives were found, and had also involved the western coast of Western Australia 13 . There may have been separate importations of the virus over time from offshore, possibly by trepang fishermen from the Dutch East Indies.…”

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confidence: 99%

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