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Published on: April 10, 2018
Serotype-specific host responses in rhesus macaques after primary dengue challenge
Andrew C Hickey1, Jacob A Koster, Claudia M Thalmann
1Department of Microbiology, National Emerging Infectious Diseases Laboratories Institute, Laboratory Animal Science Center, Boston University, Boston, Massachusetts; Venture Technologies, Penang, Malaysia; Sentinext Therapeutics, Penang, Malaysia.
Primary dengue virus (DENV) infection in macaques caused subclinical organ damage and blood coagulation activation. Serologic responses, including IgG, showed long-term persistence and serotype-specific neutralization.
Area of Science:
- Virology
- Immunology
- Pathology
Background:
- Dengue virus (DENV) is a major global health concern, causing over 100 million infections annually.
- Understanding primary DENV infection is crucial for developing effective treatments and vaccines.
- Rhesus macaques serve as a relevant model for studying human DENV infection.
Purpose of the Study:
- To characterize the in vivo effects of primary DENV infection.
- To assess clinical parameters and serologic responses following DENV infection in macaques.
- To evaluate the specificity and longevity of immune responses to DENV.
Main Methods:
- Rhesus macaques were infected with one of four DENV serotypes (DENV-1, DENV-2, DENV-3, or DENV-4).
- Clinical parameters, including blood biochemical markers, were monitored.
- Serologic responses, such as immunoglobulins and neutralizing antibodies, were assessed for specificity and duration.
Main Results:
- No overt clinical symptoms were observed, but biochemical abnormalities indicated heart, kidney, and liver damage.
- Systemic activation of the blood coagulation pathway was evident through changes in fibrinogen, D-dimers, and protein C.
- All animals developed significant homotypic and heterotypic immunoglobulins, with IgG persisting for over 390 days.
- Neutralizing antibody responses were highly serotype-specific by day 120, with some heterotypic activity noted.
Conclusions:
- Primary DENV infection in macaques leads to subclinical organ damage and coagulation pathway activation.
- Long-lasting humoral immunity, including persistent IgG and serotype-specific neutralizing antibodies, is generated.
- Further research into serotype-specific host responses may clarify mechanisms underlying severe dengue after reinfection.
