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Dengue-2 vaccine: viremia and immune responses in rhesus monkeys
Abstract:
Studies were undertaken in Indian rhesus monkeys (Macaca mulatta) to determine the safety, potency, immunogenicity, and mosquito infectivity of a small-plaque, temperature-sensitive variant of dengue type 2 (DEN-2) virus, a vaccine candidate. Fifteen monkeys were inoculated subcutaneously with the vaccine virus, ten receiving 10(3.1) plaque-forming units (PFU) and five receiving 10(4.5) PFU. After primary immunization, viremia was detected in only one monkey, a recipient of the higher dose of vaccine. The recovered virus had the same growth characteristics as the vaccine strain. Aedes aegypti mosquitoes did not become infected when they were allowed to feed on monkeys that received the lower dose of vaccine. As expected, the immunization produced no evidence of illness in any of the animals. A dose response to vaccine was detected; all five of the high-dose recipients developed neutralizing antibodies, whereas only five of ten low-dose recipients did so. In both groups, neutralizing antibody was often transient. Its presence at 30 days did not always correlate with protection from viremia in those animals challenged 4 to 6 months after vaccination with wild-type DEN-2 virus. However, immunized animals developed anamnestic antibody responses after challenge, and none demonstrated adverse effects to infection. Reimmunization of monkeys 4 months after primary immunization led to the production of low-titered but persistent neutralizing antibody which protected the animals from a wild-type virus challenge.
Insights
This study evaluated a dengue type 2 (DEN-2) vaccine candidate in rhesus monkeys. The vaccine showed promise, inducing protective antibodies after re-vaccination, though initial antibody responses were transient.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Dengue virus poses a significant global health threat.
- Development of effective dengue vaccines is a priority.
- A temperature-sensitive variant of dengue type 2 (DEN-2) virus was developed as a vaccine candidate.
Purpose of the Study:
- To assess the safety, potency, and immunogenicity of a DEN-2 vaccine candidate in Indian rhesus monkeys.
- To evaluate the vaccine's ability to prevent viremia and mosquito infectivity.
- To determine the protective efficacy against wild-type DEN-2 virus challenge.
Main Methods:
- Subcutaneous inoculation of rhesus monkeys with two doses (10(3.1) and 10(4.5) plaque-forming units) of the DEN-2 vaccine candidate.
- Monitoring for viremia, antibody responses (neutralizing antibodies), and clinical signs post-vaccination.
- Challenging vaccinated monkeys with wild-type DEN-2 virus 4–6 months after primary immunization.
- Assessing mosquito infectivity (Aedes aegypti) after feeding on vaccinated monkeys.
Main Results:
- The vaccine was safe, causing no illness in any animals.
- Viremia was minimal after primary immunization, occurring in only one high-dose recipient.
- A dose-dependent antibody response was observed, with higher antibody titers in the high-dose group.
- Neutralizing antibodies were often transient and did not always correlate with protection from viremia upon initial challenge.
- Re-vaccination led to persistent, low-titered neutralizing antibodies that conferred protection against wild-type DEN-2 challenge.
- Mosquitoes feeding on low-dose recipients did not become infected.
Conclusions:
- The small-plaque, temperature-sensitive DEN-2 vaccine candidate is safe and immunogenic in rhesus monkeys.
- A single dose may not induce consistently protective immunity, but re-vaccination can elicit persistent protective antibodies.
- The vaccine candidate shows potential for dengue prevention, warranting further investigation.