The Vaccine Origin of the 1968 Epidemic of Type 3 Poliomyelitis in Poland

Martı́n, Javier; Ferguson, Geraldine; Wood, David; Minor, Philip D.

doi:10.1006/viro.2000.0614

Cited by 33 publications

(17 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transmissibility of a live attenuated virus vaccine by mosquitoes is unacceptable because it places unvaccinated individuals at risk of infection, either by the original vaccine candidate or by more virulent derivatives created by the loss of attenuating mutations. 8,9 In the current study, 2A⌬30 demonstrated a reduced capability for infecting the midgut and for causing a disseminated infection in mosquitoes infected by artificial membrane feeding. Furthermore, 2A⌬30 was not transmitted from vaccinees to mosquitoes that were allowed to feed on the vaccinees during a period of viremia.…”

Section: Discussionmentioning

confidence: 51%

“…The candidate should not be transmissible from humans to mosquitoes to prevent both the introduction of dengue virus into new environments and the loss of the attenuation phenotype that can result from sustained transmission of live virus vaccines. 8,9 Recombinant DNA technology has greatly facilitated the development of live attenuated vaccines for dengue and other flaviviruses. [10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A live attenuated recombinant dengue-4 virus vaccine candidate with restricted capacity for dissemination in mosquitoes and lack of transmission from vaccinees to mosquitoes.

Troyer¹,

Hanley²,

Whitehead³

et al. 2001

The American Journal of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

Abstract. 2A⌬30 is a live dengue-4 virus vaccine candidate with a 30-nucleotide deletion in its 3Ј-untranslated region. To assess the transmissibility of 2A⌬30 by mosquitoes, we compared its in vivo replication in mosquitoes with that of its wild type DEN-4 parent. Both the vaccine candidate and wild type virus were equally able to infect the mosquito Toxorhynchites splendens after intrathoracic inoculation. Relative to its wild type parent, 2A⌬30 was slightly restricted in its ability to infect the midgut of Aedes aegypti mosquitoes fed on an artificial blood meal and was even more restricted in its ability to disseminate from the midgut to the salivary glands. Thus, the 30-nucleotide deletion rendered the vaccine candidate more sensitive than its wild type parent to the mosquito midgut escape barrier. Most significantly, 2A⌬30 was not transmitted to 352 Ae. albopictus mosquitoes fed on 10 vaccinees, all of whom were infected with the vaccine candidate.

show abstract

Section: Discussionmentioning

confidence: 51%

Section: Introductionmentioning

confidence: 99%

A live attenuated recombinant dengue-4 virus vaccine candidate with restricted capacity for dissemination in mosquitoes and lack of transmission from vaccinees to mosquitoes.

Troyer¹,

Hanley²,

Whitehead³

et al. 2001

The American Journal of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

show abstract

“…Mononucleotide and dinucleotide frequencies and codon usage were analyzed in the original reports of poliovirus genomic sequences (36,57,61,70). The mono-, di-, and trinucleotide frequency patterns are similar for the three Sabin strains (70) and appear to be conserved across poliovirus genotypes (24,35,39,42,46,78) and other human enterovirus species C serotypes (8). As with other enteroviruses, the component bases in the Sabin 2 open reading frame (ORF) are present in approximately equal proportions (24.0% U, 22.9% C, 29.9% A, and 23.1% G) (59,70), a property favorable to a low bias in codon usage (53).…”

Section: Resultsmentioning

confidence: 99%

Modulation of Poliovirus Replicative Fitness in HeLa Cells by Deoptimization of Synonymous Codon Usage in the Capsid Region

Burns

Shaw

Campagnoli

et al. 2006

J Virol

228

282

View full text Add to dashboard Cite

We replaced degenerate codons for nine amino acids within the capsid region of the Sabin type 2 oral poliovirus vaccine strain with corresponding nonpreferred synonymous codons. Codon replacements were introduced into four contiguous intervals spanning 97% of the capsid region. In the capsid region of the most highly modified virus construct, the effective number of codons used (N C ) fell from 56.2 to 29.8, the number of CG dinucleotides rose from 97 to 302, and the G؉C content increased from 48.4% to 56.4%. Replicative fitness in HeLa cells, measured by plaque areas and virus yields in single-step growth experiments, decreased in proportion to the number of replacement codons. Plaque areas decreased over an ϳ10-fold range, and virus yields decreased over an ϳ65-fold range. Perhaps unexpectedly, the synthesis and processing of viral proteins appeared to be largely unaltered by the restriction in codon usage. In contrast, total yields of viral RNA in infected cells were reduced ϳ3-fold and specific infectivities of purified virions (measured by particle/PFU ratios) decreased ϳ18-fold in the most highly modified virus. The replicative fitness of both codon replacement viruses and unmodified viruses increased with the passage number in HeLa cells. After 25 serial passages (ϳ50 replication cycles), most codon replacements were retained, and the relative fitness of the modified viruses remained well below that of the unmodified virus. The increased replicative fitness of high-passage modified virus was associated with the elimination of several CG dinucleotides. Potential applications for the systematic modulation of poliovirus replicative fitness by deoptimization of codon usage are discussed.The use of synonymous codons at unequal frequencies, the codon usage bias, is characteristic of all biological systems (26,27). The strength and direction of codon usage bias are related to the genomic GϩC content and the relative abundance of different isoaccepting tRNAs (reviewed in references 1, 16, and 53). Codon usage can affect the efficiency of gene expression. In bacteria (Escherichia coli) (26, 75), yeast (Saccharomyces cerevisiae) (5, 27), plants (Arabidopsis thaliana) (12), nematodes (Caenorhabditis elegans) (16), and insects (Drosophila melanogaster) (50), the most highly expressed genes use codons matched to the most abundant tRNAs (2). In contrast, in humans and other vertebrates, codon usage bias is much more strongly correlated with the GϩC content of the isochore where the gene is located (51, 71) than with the breadth or level of gene expression (16) or the number of corresponding tRNA genes (28, 30). Despite the weak correlation between codon usage and the levels of gene expression in mammalian cells (16,71), imbalances between codon usage and tRNA abundance can sharply reduce the levels of gene expression.Optimization of codon composition is frequently required for the efficient expression of genes in heterologous host systems (3,31,67,76). For example, the expression of human immunodeficiency virus type 1 ...

show abstract

“…However, the possibility that antigenic poliovirus variants such as strain 31043 could establish widespread infections in suboptimally vaccinated populations cannot be excluded. Low levels of protective antibodies against poliovirus in the population as a consequence of inadequate vaccination and the atypical antigenic properties of epidemic strains were identified as key factors in the establishment of outbreaks of type 3 poliomyelitis in Poland (1968) (28) and Finland (1984) (19). The outbreak in Poland involved poliovirus strains derived from the USOL-Dbac vaccine virus, which was used in a small trial.…”

Section: Discussionmentioning

confidence: 99%

Isolation of an Intertypic Poliovirus Capsid Recombinant from a Child with Vaccine-Associated Paralytic Poliomyelitis

Martı́n

Самойлович

Dunn

et al. 2002

J Virol

Self Cite

View full text Add to dashboard Cite

The isolation of a capsid intertypic poliovirus recombinant from a child with vaccine-associated paralytic poliomyelitis is described. Virus 31043 had a Sabin-derived type 3-type 2-type 1 recombinant genome with a 5-end crossover point within the capsid coding region. The result was a poliovirus chimera containing the entire coding sequence for antigenic site 3a derived from the Sabin type 2 strain. The recombinant virus showed altered antigenic properties but did not acquire type 2 antigenic characteristics. The significance of the presence in nature of such poliovirus chimeras and the consequences for the current efforts to detect potentially dangerous vaccine-derived poliovirus strains are discussed in the context of the global polio eradication initiative.Poliovirus, the agent responsible for paralytic poliomyelitis, is a human enterovirus member of the family Picornaviridae, a group of nonenveloped positive-strand RNA viruses. The coding region of the genome is preceded by a long 5Ј noncoding region (NCR) of approximately 740 nucleotides that contains important determinants of virulence. The 3Ј end of the genome consists of a short NCR of about 70 nucleotides that is also implicated in RNA replication (33). The coding region is translated as a single polyprotein and is then processed to generate the viral capsid (VP1 to VP4) and the nonstructural proteins. The antigenic determinants for poliovirus-neutralizing antibodies are located on surface-exposed loops in the capsid proteins VP1, VP2, and VP3. Four main antigenic sites have been identified by the use of murine monoclonal antibodies (MAbs) (30).Genomic RNA recombination is a common event during poliovirus evolution. The oral poliovaccine (OPV) consists of live attenuated strains of the three polio serotypes, which replicate in the guts of immunocompetent vaccinees for periods that range between several weeks and 3 months. A high proportion of type 2 and type 3 polio isolates excreted by healthy vaccinees and patients with vaccine-associated paralytic poliomyelitis (VAPP), have been found to be intertypic recombi-

show abstract

The Vaccine Origin of the 1968 Epidemic of Type 3 Poliomyelitis in Poland

Cited by 33 publications

References 14 publications

A live attenuated recombinant dengue-4 virus vaccine candidate with restricted capacity for dissemination in mosquitoes and lack of transmission from vaccinees to mosquitoes.

A live attenuated recombinant dengue-4 virus vaccine candidate with restricted capacity for dissemination in mosquitoes and lack of transmission from vaccinees to mosquitoes.

Modulation of Poliovirus Replicative Fitness in HeLa Cells by Deoptimization of Synonymous Codon Usage in the Capsid Region

Isolation of an Intertypic Poliovirus Capsid Recombinant from a Child with Vaccine-Associated Paralytic Poliomyelitis

Contact Info

Product

Resources

About