Cross-Protection Studies and Search for Subclinical Disease in New World Monkeys Infected Sequentially With Different Immunologic Types of Dengue Viruses1

Scherer, W. F., F. A. Breakenridge and R. W. Dickerman (Cornell Univ. Medical College, New York, N.Y. 10021). Cross protection studies and search for subclinical disease in New World monkeys infected sequentially with different immunologic types of dengue viruses. Am J Epidemiol 95: 67–79, 1972.–Squirrel monkeys, Saimiri sciureus, and marmosets, Saguinus oedipus developed homologous HI antibodies after primary subcutaneous inoculation of several strains of types 1–3 dengue viruses though not after two type 4 strains. Viremias were detected irregularly, usually at low levels and more frequently with high-passaged, mouse-adapted strains and mouse tests for viremia than with low-passaged, rhesus kidney culture strains and direct plaque tests in LLCMK2 rhesus kidney cultures. Types 1–3 given intranasally produced antibody responses in some squirrel monkeys, marmosets and night monkeys (Aotus trivergatus). Neutralizing and HI antibodies to types 1–4 dengue viruses were not detected in preinoculation monkey sera. Secondary viremias occurred in squirrel monkeys and marmosets after sequences of virus types 2 + 3, 3 + 2, 1+2 and 1+3 given subcutaneously or intravenously 58–310 days apart. Heterologous secondary challenges with types 2 and 3 and tertiary challenges with types 1 and 3 produced significant rises in HI antibody titers to the challenge virus. Rises in type 3 HI antibody titers occurred in three squirrel monkeys given type 3 virus, strain 16562 from Thailand, subcutaneously a year after type 3, strain Pak-20 from East Pakistan. No signs of overt or subclinical disease could be detected in primarily infected or challenged squirrel monkeys or marmosets using measurements of body temperature, leucocyte and platelet concentrations of blood or hematocrits.