Non-Human Primate Models of Dengue Virus Infection: A Comparison of Viremia Levels and Antibody Responses during Primary and Secondary Infection among Old World and New World Monkeys

Abstract

Due to the global burden of dengue disease, a vaccine is urgently needed. One of the key points in vaccine development is the development of a robust and reliable animal model of dengue virus infection. Characteristics including the ability to sustain viral replication, demonstration of clinical signs, and immune response that resemble those of human dengue virus infection are vital in animal models. Preclinical studies in vaccine development usually include parameters such as safety evaluation, induction of viremia and antigenemia, immunogenicity, and vaccine effectiveness. Although mice have been used as a model, non-human primates have an advantage over mice because of their relative similarity to humans in their genetic composition and immune responses. This review compares the viremia kinetics and antibody responses of cynomolgus macaques (Macaca fasicularis), common marmosets (Callithrix jacchus), and tamarins (Saguinus midas and Saguinus labitus) and summarize the perspectives and the usefulness along with challenges in dengue vaccine development.

Suppression of dengue virus replication by the French maritime pine extract Pycnogenol®

“…The DENV strains used in this study were DENV1 NIID 02-17 (GenBank accession number AB111075), DENV2 NIID 00-43 (AB111452) ( Ito et al., 2007 ), DENV3 DSS 1403 (GenBank accession number AB189125) ( Muhammad Azami et al., 2020 ), and DENV4 NIID 05-40. These viruses were propagated in Vero or baby hamster kidney (BHK) cells.…”

Molecular Mechanisms of Antiviral Agents against Dengue Virus

“…Currently, there are no animal models which can reproduce the same symptoms or clinical manifestations of dengue infections as observed in humans. Various non-human primate models such as rhesus macaques, bonnet monkeys, olive baboons, and African green monkeys have been used for the development of vaccines or antibody-based therapies against dengue [ 46 ]. However, antiviral drugs are seldom evaluated in these non-human primate models due to issues such as high production costs, difficulty in breeding large numbers of animals, and the absence of severe dengue symptoms mirroring that in humans.…”

Aedes-borne orthoflavivirus infections in neotropical primates – Ecology, susceptibility, and pathogenesis

“…54 The taxonomic proximity of NHPs and humans is greater than that of any other animal models, and therefore, these animals are important to understanding the pathogenesis and immune responses to DENV infection. 55…”