To support the licensure of a new and safer
vaccine to protect people against
smallpox, a
monkeypox model of
infection in cynomolgus macaques, which simulates
smallpox in humans, was used to evaluate two
vaccines,
Acam2000 and
Imvamune, for protection against disease. Animals vaccinated with a single immunization of
Imvamune were not protected completely from severe and/or lethal
infection, whereas those receiving either a prime and boost of
Imvamune or a single immunization with
Acam2000 were protected completely. Additional parameters, including clinical observations, radiographs, viral load in blood, throat swabs, and selected tissues, vaccinia virus-specific antibody responses, immunophenotyping, extracellular
cytokine levels, and histopathology were assessed. There was no significant difference (P > 0.05) between the levels of
neutralizing antibody in animals vaccinated with a single immunization of
Acam2000 (132 U/ml) and the prime-boost
Imvamune regime (69 U/ml) prior to challenge with monkeypox virus. After challenge, there was evidence of viral excretion from the throats of 2 of 6 animals in the prime-boost
Imvamune group, whereas there was no confirmation of excreted live virus in the
Acam2000 group. This evaluation of different human
smallpox vaccines in cynomolgus macaques helps to provide information about optimal
vaccine strategies in the absence of human challenge studies.