Smallpox eradication, laboratory visits, and a touch of tourism: travel notes of a Canadian scientist in Brazil

Palmer, Steven; Hochman, Gilberto; Arbex, Danieli

doi:10.1590/s0104-59702010000300012

Cited by 5 publications

(4 citation statements)

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“…The major smallpox vaccine producer in Brazil, among three others, was Instituto Oswaldo Cruz in Rio de Janeiro (1,14). VACV strain IOC (VACV-IOC) was exclusively used by the Institute to manufacture the vaccine that was widely distributed in Brazil during the eradication campaign (1).…”

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“…VACV strain IOC (VACV-IOC) was exclusively used by the Institute to manufacture the vaccine that was widely distributed in Brazil during the eradication campaign (1). The vaccine was produced in calf skin or chicken eggs (14) and usually had take rates of Ͼ98% (1) and low rates of adverse effects (H. Schatzmayr, personal communication). Unfortunately, poor documentation resulted in scant existing information about the origins of VACV-IOC.…”

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Genomic Analysis, Phenotype, and Virulence of the Historical Brazilian Smallpox Vaccine Strain IOC: Implications for the Origins and Evolutionary Relationships of Vaccinia Virus

Medaglia

Moussatché

Nitsche

et al. 2015

J Virol

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Smallpox was declared eradicated in 1980 after an intensive vaccination program using different strains of vaccinia virus (VACV; Poxviridae). VACV strain IOC (VACV-IOC) was the seed strain of the smallpox vaccine manufactured by the major vaccine producer in Brazil during the smallpox eradication program. However, little is known about the biological and immunological features as well as the phylogenetic relationships of this first-generation vaccine. In this work, we present a comprehensive characterization of two clones of VACV-IOC. Both clones had low virulence in infected mice and induced a protective immune response against a lethal infection comparable to the response of the licensed vaccine ACAM2000 and the parental strain VACV-IOC. Full-genome sequencing revealed the presence of several fragmented virulence genes that probably are nonfunctional, e.g., F1L, B13R, C10L, K3L, and C3L. Most notably, phylogenetic inference supported by the structural analysis of the genome ends provides evidence of a novel, independent cluster in VACV phylogeny formed by VACV-IOC, the Brazilian field strains Cantagalo (CTGV) and Serro 2 viruses, and horsepox virus, a VACV-like virus supposedly related to an ancestor of the VACV lineage. Our data strongly support the hypothesis that CTGV-like viruses represent feral VACV that evolved in parallel with VACV-IOC after splitting from a most recent common ancestor, probably an ancient smallpox vaccine strain related to horsepox virus. Our data, together with an interesting historical investigation, revisit the origins of VACV and propose new evolutionary relationships between ancient and extant VACV strains, mainly horsepox virus, VACV-IOC/CTGV-like viruses, and Dryvax strain. IMPORTANCEFirst-generation vaccines used to eradicate smallpox had rates of adverse effects that are not acceptable by current health care standards. Moreover, these vaccines are genetically heterogeneous and consist of a pool of quasispecies of VACV. Therefore, the search for new-generation smallpox vaccines that combine low pathogenicity, immune protection, and genetic homogeneity is extremely important. In addition, the phylogenetic relationships and origins of VACV strains are quite nebulous. We show the characterization of two clones of VACV-IOC, a unique smallpox vaccine strain that contributed to smallpox eradication in Brazil. The immunogenicity and reduced virulence make the IOC clones good options for alternative second-generation smallpox vaccines. More importantly, this study reveals the phylogenetic relationship between VACV-IOC, feral VACV established in nature, and the ancestor-like horsepox virus. Our data expand the discussion on the origins and evolutionary connections of VACV lineages. S mallpox, caused by variola virus (genus Orthopoxvirus, family Poxviridae), accounted for millions of deaths throughout human history. The disease was declared eradicated in 1980 after a worldwide program implemented by the WHO involving strict surveillance and intensive vaccination using vaccinia vi...

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Genomic Analysis, Phenotype, and Virulence of the Historical Brazilian Smallpox Vaccine Strain IOC: Implications for the Origins and Evolutionary Relationships of Vaccinia Virus

Medaglia

Moussatché

Nitsche

et al. 2015

J Virol

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“…In Brazil, the Oswaldo Cruz Institute in Rio de Janeiro was the main manufacturer of smallpox vaccines distributed nationwide as part of the systematic vaccination program [ 9 , 10 ]. Calf-based vaccines were preferentially used and were manufactured with VACV strain IOC, which probably derived from the Beaugency lymph brought to Brazil from France in the late 19th century and was exclusively produced in Brazil.…”

Section: Introductionmentioning

confidence: 99%

“…Calf-based vaccines were preferentially used and were manufactured with VACV strain IOC, which probably derived from the Beaugency lymph brought to Brazil from France in the late 19th century and was exclusively produced in Brazil. The other three production centers in Brazil used different VACV strains [ 1 , 10 ]. On some occasions, seed stocks of Wyeth-based smallpox vaccine were supplied to the Brazilian program by Wyeth Pharmaceuticals to overcome temporary supply shortages in the 1970s (Wilson RJ to Henderson DA, Sanofi Pasteur archives, 8 September 1970, personal communication).…”

Section: Introductionmentioning

confidence: 99%

Genomic Characterization of the Historical Smallpox Vaccine Strain Wyeth Isolated from a 1971 Seed Vial

Cruz

Luques

Castiñeiras

et al. 2022

Viruses

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The Wyeth strain of vaccinia virus (VACV) produced by Wyeth Pharmaceuticals was supposedly used to manufacture the old freeze-dried American smallpox vaccine, Dryvax, until its discontinuation in 2008. Although the genomic sequences of numerous Dryvax clones have been reported, data on VACV-Wyeth genomes are still lacking. Genomic analysis of old VACV strains is relevant to understand the evolutionary relationships of smallpox vaccines, particularly with the recent resumption of smallpox vaccination in certain population groups as an attempt to control the worldwide monkeypox outbreak. Here we analyzed the complete genome sequences of three VACV-Wyeth clonal isolates obtained from a single seed vial donated to the Brazilian eradication program in the 1970s. Wyeth clones show >99.3% similarity to each other and >95.3% similarity with Dryvax clones, mapping together in clade I of the vaccinia group. Although the patterns of SNPs and INDELs comparing Dryvax and Wyeth clones are overall uniform, important differences were detected particularly at the ends of the genome. In addition, we detected recombinant events of clone Wyeth A111 and the Dryvax clone Acam2000, suggesting that other regions of the genomes may have similar patchy patterns of recombination. A small-scale serological survey using VACV-Wyeth as antigen in ELISA assays revealed that 63 of the 65 individuals born before the end of smallpox vaccination in Brazil still have anti-VACV IgG antibodies, demonstrating the usefulness of the VACV-Wyeth strain in future extended serological studies of the Brazilian population.

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Revisiting Jenner's mysteries, the role of the Beaugency lymph in the evolutionary path of ancient smallpox vaccines

Damaso

2018

The Lancet Infectious Diseases

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Smallpox eradication, laboratory visits, and a touch of tourism: travel notes of a Canadian scientist in Brazil

Abstract: Erradicando a varíola, visitando laboratórios e um pouco de turismo: notas de viagem de um cientista canadense ao Brasil

Cited by 5 publications

References 3 publications

Genomic Analysis, Phenotype, and Virulence of the Historical Brazilian Smallpox Vaccine Strain IOC: Implications for the Origins and Evolutionary Relationships of Vaccinia Virus

Genomic Analysis, Phenotype, and Virulence of the Historical Brazilian Smallpox Vaccine Strain IOC: Implications for the Origins and Evolutionary Relationships of Vaccinia Virus

Genomic Characterization of the Historical Smallpox Vaccine Strain Wyeth Isolated from a 1971 Seed Vial

Revisiting Jenner's mysteries, the role of the Beaugency lymph in the evolutionary path of ancient smallpox vaccines

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