Experimental Measles. II. Infection and Immunity in the Rhesus Macaque

Abstract

Measles infection and the host immune response to measles virus was compared using naive and immunized rhesus monkeys. The monkeys were experimentally challenged with a wild-type strain of measles virus inoculated intranasally. After pathogenic virus challenge, measles virus was detected in mononuclear cells of peripheral blood, lymph node, and spleen in naive monkeys and viremia peaked on Day 7. However, only one of five vaccinated monkeys had a lower virus titer in peripheral blood mononuclear cells at one time point after challenge. No virus was detected in the lymphoid tissues from an immunized monkeys that was euthanized on Day 7 of infection. Measles-specific IgM, IgG, neutralizing antibody, and cytotoxic T lymphocytes were detected in vaccinated monkeys before challenge, but antibody titers were significantly lower in immunized monkeys than in naive monkey after challenge. Measles-specific IgG antibody and cytotoxic T cell responses were still detected more than 1 year after vaccination or infection. This animal model is useful for the further study of measles pathogenesis, immunosuppression, and immunologic memories.

Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed

“…All animal experiments were approved by the UC Davis Chancellor's Animal Use and Care Administrative Advisory Committee. For consistency with previous experiments, the TCID50 of the virus stock was determined by endpoint dilution coculture with Raji cells, as described previously (50). Six animals were inoculated with 10 4.5 TCID50 of WT-HDOUBLE in a volume of 1 ml by a single drop onto the conjunctiva of each eye and the remainder divided into both nares.…”

“…Four replicates of 10 1 to 10 5 PBMCs were cocultured with 10 5 Raji cells per well in 24-well plates (Fisher Scientific), and 10 6 PBMCs were cocultured with 10 6 Raji cells in T25 flasks. The cultures were maintained for 2 weeks, monitored for large multinucleated giant cell formation, and scored for cytopathic effect by light microscopy (50). At the same time points, tracheal aspirates were taken and centrifuged and the cell pellet tested for MV by coculture with Raji cells.…”

“…At the same time points, tracheal aspirates were taken and centrifuged and the cell pellet tested for MV by coculture with Raji cells. Neutralizing antibody against MV was measured as described previously (50).…”

Morbilliviruses and human disease

“…The cotton rat model mimics aspects of immunosuppression of MV in the human [176,177]. The most realistic model that mimics MV infection in humans is that of infection in macaques [34,[178][179][180][181][182][183][184], but the cost of these animals is high and small numbers are available. Rash is shown as a reliable indicator of the value of a model.…”

Tropism illuminated: Lymphocyte-based pathways blazed by lethal morbillivirus through the host immune system

“…Only primates develop a measles-like disease (14)(15)(16); initial attempts to produce appropriately genetically modified mice have been only partially successful (17)(18)(19). Thus, other experimental paradigms have been sought (20), and recently a model of morbillivirus-induced pathogenesis was developed in ferrets, one of the natural canine distemper virus (CDV) hosts.…”