Viremia and antibody response in green monkeys (Chlorocebus aethiops sabaeus) infected with dengue virus type 2: A potential model for vaccine testing

Abstract

The increasingly limited availability and high cost of the hitherto most commonly used monkey species in dengue vaccine research has augmented the importance of identifying alternative suitable models for these studies. In this study we examined the capacity of green monkeys (Chlorocebus aethiops sabaeus) to develop dengue viremia, and thus provide a potential model for dengue vaccine testing. Monkeys were inoculated with two different doses of dengue virus type 2. All animals in both groups became viremic after inoculation of the virus. In the lower dose group, mean viremia duration of 5.66 days was detected, whereas in the group that received the 10 6 PFU dose, viremia had a mean duration of only 1.66 days. Antibody titers were similar to those obtained in previous experiments with rhesus and cynomolgus macaques. We conclude that green monkeys develop viremia and antibody responses and therefore provide a potential model for the preclinical evaluation of novel candidates for dengue vaccines.

The Chimeric Protein Domain III-Capsid of Dengue Virus Serotype 2 (DEN-2) Successfully Boosts Neutralizing Antibodies Generated in Monkeys upon Infection with DEN-2

“…The virus was efficiently isolated from the sera of the infected animals, with a mean of 4.67 days of viremia. These results are similar to those previously described by Martín et al in 2009 for this monkey species (19).…”

“…After administration of the viral infective dose to monkeys, a consistent viremia was detected, indicating a successful infection. The day of mean viremia was similar to that previously reported by our group in different green monkey assays (19,20,28). The humoral immune response measured by ELISA reached maximal values at day 30 after infection, whereas titers of neutralizing antibodies had maximal values between days 60 and 90 postinfection.…”

Viral kinetics of primary dengue virus infection in non-human primates: A systematic review and individual pooled analysis

“…This phenomenon was observed by Martin et al in green monkeys [27], in yellow fever virus (YFV) infections in rhesus monkeys [28], chimeric YF-DENV vaccine in cynomolgus macaques [29] and in humans receiving a live, attenuated Japanese Encephalitis vaccine (ChimeriVax-JE) [30, 31] and a live, attenuated West Nile virus vaccine [32]. It could be that a large inoculating dose causes a rapid initial rise in viremia inducing a stronger innate immune response leading to quicker clearance.…”

The tortoise or the hare? Impacts of within-host dynamics on transmission success of arthropod-borne viruses

“…These findings suggest an inherent trade-off between duration and magnitude of viraemia. Moreover, we favour the interpretation, initially suggested by some of the authors of these studies, that this trade-off is mediated by the immune response to infection, and that a higher infecting dose enables more rapid virus replication but a concomitantly rapid and strong immune response [44,45]. An alternative explanation for this trade-off is resource limitation-i.e.…”