Lack of greater seroconversion of rhesus monkeys after subcutaneous inoculation of dengue type 2 live-virus vaccine combined with infection-enhancing antibodies

A dengue-2 live virus vaccine was tested in monkeys immune to heterologous dengue serotypes to determine if, as with wild DEN-2 virus, antibody-enhanced viraemia and seroconversion would occur. A low dose of 900 plaque-forming units (PFU) of the DEN-2/S-1 vaccine virus was inoculated subcutaneously into rhesus monkeys six months after they had received wild DEN-1, DEN-2 or DEN-3 viruses, and into non-immune monkeys. As previously reported for non-immune monkeys, there was little, if any, detectable vaccine viraemia in any of the groups of monkeys. There was no difference in seroconversion between the dengue heterologously immune (3/6) and non-immune (1/3) monkeys. These data indicated that (i) the vaccine virus may differ from the parent virus in the ability to complex with heterologous antibody and, thus, in the ability to infect Fc receptor bearing cells in monkeys; (ii) 10(3) PFU of vaccine virus is approximately the 50% infectious dose in monkeys as measured by seroconversion.

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Lack of viraemia and limited antibody response of dengue virus immune rhesus monkeys after vaccination with DEN-2/S-1 vaccine

Kraiselburd

Kessler

Torres-Blasini

1984

Transactions of the Royal Society of Tropical Medicine and Hygi

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Quantity of dengue virus required to infect rhesus monkeys

Kraiselburd

Gubler

Kessler³

1985

Transactions of the Royal Society of Tropical Medicine and Hygi

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As part of a dengue vaccine study, it was necessary to determine how much virus was required to infect rhesus monkeys. Serial dilutions of dengue 2 and 4 viruses were inoculated subcutaneously into groups of five monkeys and seroconversions determined on days 30 and 60 post-inoculation. The viruses were also titrated simultaneously in LLC-MK2 cells and mosquitoes. It was calculated that 9.5 mosquito infectious doses 50 (MID50) of dengue 2 virus and 22 MID50 of dengue 4 virus were required to infect 50% of the monkeys. The data suggest that 100 MID50 of dengue virus should be used as a challenge dose for monkeys previously immunized with dengue vaccine.

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Decreases in dengue transmission may act to increase the incidence of dengue hemorrhagic fever

Nagao

Koelle

2008

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

148

173

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Dengue hemorrhagic fever (DHF) is a potentially fatal manifestation of an infection with the mosquito-borne dengue virus. Because of the social and economic costs of DHF, many countries in Asia and South America have initiated public health measures aimed at vector control. Despite these measures, DHF incidence rates do not appear to be declining. The effectiveness of vector control in reducing dengue transmissibility has thereby been questioned. Here, we revisit this conclusion using epidemiological data from Thailand. We first show, with age incidence data, that dengue transmission rates have fallen since 1981; surprisingly, however, these declines are not associated with decreases in DHF incidence. Instead, district-level analyses indicate a nonmonotonic relationship between the basic reproductive number R 0 and DHF incidence. To understand this relationship, we formulated three mathematical models, which differ in their assumptions of transient between-serotype cross-protection. Unlike the first two models, the previously unconsidered third model with clinical cross-protection can reproduce this nonmonotonic relationship. Simulation of this model with nonstationary R 0 reproduces several previously unexplained patterns of dengue dynamics, including a transition from a Ϸ2-year cycle to a Ϸ4-year cycle and a transient trough in DHF incidence in provinces with rapid R 0 declines. These results imply that DHF incidence can be effectively controlled with a sufficiently large reduction in R 0 but that moderate reductions may be counterproductive. More broadly, these results show that assuming parameter stationarity in systems with approximate stationarity in disease incidence is unjustified and may result in missed opportunities to understand the drivers of disease variability.dengue dynamics ͉ interannual disease variability ͉ multistrain dynamics

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Lack of greater seroconversion of rhesus monkeys after subcutaneous inoculation of dengue type 2 live-virus vaccine combined with infection-enhancing antibodies

Cited by 4 publications

References 16 publications

Lack of viraemia and limited antibody response of dengue virus immune rhesus monkeys after vaccination with DEN-2/S-1 vaccine

Lack of viraemia and limited antibody response of dengue virus immune rhesus monkeys after vaccination with DEN-2/S-1 vaccine

Quantity of dengue virus required to infect rhesus monkeys

Decreases in dengue transmission may act to increase the incidence of dengue hemorrhagic fever

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