Infection, Dissemination, Transmission, and Biological Attributes of Dengue-2 PDK53 Candidate Vaccine Virus after Oral Infection in Aedes aegypti

Khin, Mi Mi; Jirakanjanakit, Nuananong; Yoksan, Sutee; Bhamarapravati, Natth

doi:10.4269/ajtmh.1994.51.864

Cited by 26 publications

(27 citation statements)

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“…Nonetheless, the relatively high level of infectivity of 2A⌬30 for the mosquito midgut differs from that of many previous vaccine candidates, which are poorly infectious for the midgut. [27][28][29][30] However, the OID 50 necessary for a disseminated infection was approximately 10-fold higher for 2A⌬30 than for its parent virus, indicating that 2A⌬30 is restricted in its ability to cross the midgut barrier. This interpretation was strengthened by the results from intrathoracic inoculation of T. splendens with the two viruses.…”

Section: Discussionmentioning

confidence: 97%

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

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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.

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Section: Discussionmentioning

confidence: 97%

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

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“…For example, the parental strain of a live-attenuated DEN-2 vaccine proved to be about five times more infectious to mosquitoes than its vaccine derivative. 26 Whole genome sequencing revealed that the vaccine strain actually represents a mixture of two genetic variants that vary at one amino acid position and these variants differ from the parental strain by seven or eight amino acids. 27 The SE Asian and American genotypes of DEN-2 virus may be distinguished by 11 amino acid changes in the coding region and by 7 nucleotide substitutions and 10 deletions in the non-coding regions of the genome.…”

Section: Discussionmentioning

confidence: 99%

Efficiency of Dengue Serotype 2 Virus Strains to Infect and Disseminate in Aedes Aegypti

Armstrong

Rico-Hesse

2003

The American Journal of Tropical Medicine and Hygiene

130

120

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Abstract. Dengue serotype 2 (DEN-2) viruses with the potential to cause dengue hemorrhagic fever have been shown to belong to the Southeast (SE) Asian genotype. These viruses appear to be rapidly displacing the American genotype of DEN-2 in the Western Hemisphere. To determine whether distinct genotypes of DEN-2 virus are better adapted to mosquito transmission, we classified 15 viral strains of DEN-2 phylogenetically and compared their ability to infect and disseminate in different populations of Aedes aegypti mosquitoes. Envelope gene nucleotide sequence analysis confirmed that six strains belonged to the American genotype and nine strains were of the SE Asian genotype. The overall rate of disseminated infection in mosquitoes from Texas was 27% for the SE Asian genotype versus 9% for the American genotype. This pattern of infection was similar in another population of mosquitoes sampled from southern Mexico (30% versus 13%). Together, these findings suggest that Ae. aegypti tends to be more susceptible to infection by DEN-2 viruses of the SE Asian genotype than to those of the American genotype, and this may have epidemiologic implications.

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“…Reduced replication of the candidate D2 PDK-53 vaccine virus in Aedes aegypti mosquitoes and C6/36 (A. albopictus) cells is a significant biological attenuation marker of the PDK-53 virus (9,25,26). PDK-53 virus is not transmitted by A. aegypti mosquitoes (25), reducing the potential for secondary transmission of the vaccine virus and providing an important safety feature for the vaccine.…”

Section: Discussionmentioning

confidence: 99%

“…PDK-53 virus is not transmitted by A. aegypti mosquitoes (25), reducing the potential for secondary transmission of the vaccine virus and providing an important safety feature for the vaccine. We and others have reported this low-replication phenotype in C6/36 cells for different DEN vaccine candidates (11,19,21,22,46).…”

Section: Discussionmentioning

confidence: 99%

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Chimeric Dengue 2 PDK-53/West Nile NY99 Viruses Retain the Phenotypic Attenuation Markers of the Candidate PDK-53 Vaccine Virus and Protect Mice against Lethal Challenge with West Nile Virus

Huang

Silengo

Whiteman

et al. 2005

J Virol

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West Nile (WN) virus, a member of the Flavivirus genus, is a mosquito-borne virus of the Japanese encephalitis (JE) serocomplex. The JE serocomplex contains viruses that cause central nervous system infections, such as JE virus in Asia; St. Louis encephalitis virus in the Americas; Rocio virus in Brazil; Murray Valley encephalitis virus in Australia, New Guinea, and New Zealand; and Kunjin virus (reclassified as subtype WN recently) in Australia (44). Before the mid 1990s, WN virus caused sporadic outbreaks of illness, ranging from fever to occasional encephalitis, in Africa, the Middle East, and Western Asia. However, since 1996, WN encephalitis in humans has been reported more frequently in Europe, the Middle East, northern and western Africa, and Russia (33). In 1999, WN virus first emerged in the western hemisphere in New York City and surrounding areas, where the virus caused the deaths of seven humans and numerous birds and horses (15,33). Since then, WN virus has spread throughout most of the continental United States, with more than 4,156 reported human cases and 284 deaths in 2002 (37) and 9,862 cases with 264 deaths in 2003 (12). WN virus activity in humans, birds, and horses has been documented in Canada, the Caribbean, and Central America. The rapid spread of WN virus suggests it may pose a significant public health problem in future years (15). There is no licensed human WN vaccine available to protect at-risk populations from WN illness.Dengue (DEN) viruses are also human pathogens that are transmitted by mosquitoes. These viruses cause illness in millions of people every year throughout tropical regions of the world. Flaviviruses of the DEN serocomplex are classified into four serotypes, DEN 1 to DEN 4 (D1 to D4). Flaviviruses contain a single-stranded positive-sense genomic RNA of approximately 11 kb with the genomic organization 5ЈNCR-CprM-E-NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5-3ЈNCR (where NCR is noncoding region, C is capsid, prM is premembrane, E is envelope, and NS is nonstructural protein). One of the most promising D2 vaccine candidates, strain PDK-53, was derived by passage of the wild-type D2 16681 virus 53 times in primary dog kidney (PDK) cells (48). To study the attenuation loci of the candidate D2 PDK-53 vaccine virus, as well as to develop effective tetravalent DEN vaccines against all four DEN serotypes, we constructed infectious cDNA clones of the D2 viruses (9, 26) and used them to engineer chimeric DEN viruses containing the prM-E genes of D1, D3, or D4 virus in the D2 genetic backbones (18,19). The uncloned D2 PDK-53 vaccine virus contains a mixture of two genotypic variants (26), designated 19) in this report. The PDK53-V variant contains all nine PDK-53 virus vaccine-specific nucleotide mutations, including the Glu-to-Val mutation at amino acid position NS3-250 (26). The PDK53-E variant contains eight of the nine mutations of the PDK-53 vaccine, and the NS3-250-Glu of its parental D2 16681 virus. Our results showed that the phenotypic markers associated with the attenuation of PDK...

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Infection, Dissemination, Transmission, and Biological Attributes of Dengue-2 PDK53 Candidate Vaccine Virus after Oral Infection in Aedes aegypti

Cited by 26 publications

References 0 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.

Efficiency of Dengue Serotype 2 Virus Strains to Infect and Disseminate in Aedes Aegypti

Chimeric Dengue 2 PDK-53/West Nile NY99 Viruses Retain the Phenotypic Attenuation Markers of the Candidate PDK-53 Vaccine Virus and Protect Mice against Lethal Challenge with West Nile Virus

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