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.

Keywords: animal model; common marmoset; cynomolgus macaque; dengue virus; non-human primate; secondary infection; tamarin; vaccine study.

Figure 1

Levels of dengue virus specific IgM and IgG antibody in cynomolgus macaques, common marmosets, and tamarins: (A) Levels of DENV-specific IgM antibody during primary infection; (B) Levels of DENV-specific IgG antibody during primary infection; (C) Levels of DENV-specific IgM antibody during secondary infection; (D) levels of DENV-specific IgG antibody during secondary infection. Levels of antibody in cynomolgus macaques (○), common marmosets (●), and tamarins (×) were determined from day 0 to 14 after primary and secondary DENV infection. The P/N ratio indicates the positive: negative ratio. The P/N ratio was calculated by using the formula: absorbance of the test sample/absorbance of the negative control. The P/N ratio_day0 is defined as the level of DENV-specific IgM or IgG antibody on the day of virus inoculation. DENV, dengue virus; Ig G, immunoglobulin G; Ig M, immunoglobulin M.