title: Experimental infection of Cynomolgus Macaques (Macaca fascicularis) with human varicella-zoster virus.
abstract: Varicella-zoster virus (VZV) is a member of the alphaherpesvirus family and the causative agent of chickenpox and shingles. To determine the utility of cynomolgus macaques (Macaca fascicularis) as a nonhuman primate model to evaluate VZV-based simian immunodeficiency virus/human immunodeficiency virus (SIV/HIV) vaccines, we experimentally inoculated 10 animals with the parental Oka (Oka-P) strain of VZV derived from MeWo or Telo-RF cells. VZV DNA could be detected in the lungs as late as 4 days postinfection, with replicating virus detected by shell vial culture assay in one case. Infection did not result in any overt clinical symptoms but was characterized by humoral and cell-mediated immunity in a time frame and at a magnitude similar to those observed following VZV vaccination in humans. The cell line source of VZV inoculum influenced both the magnitude and polyfunctionality of cell-mediated immunity. Animals mounted a vigorous anamnestic antibody response following a second inoculation 12 weeks later. Inoculations resulted in transient increases in CD4(+) T-cell activation and proliferation, as well as a sustained increase in CD4(+) T cells coexpressing CCR5 and α4β7 integrin. In contrast to previous failed attempts to successfully utilize attenuated VZV-Oka as an SIV vaccine vector in rhesus macaques due to suboptimal infectivity and cellular immunogenicity, the ability to infect cynomolgus macaques with Oka-P VZV should provide a valuable tool for evaluating VZV-vectored SIV/HIV vaccines.
authors.affiliation: Department of Microbiology, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: David O
authors.initials: DO
authors.lastname: Willer
authors.forename: Aruna P N
authors.initials: AP
authors.lastname: Ambagala
authors.forename: Richard
authors.initials: R
authors.lastname: Pilon
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Chan
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Fournier
authors.forename: James
authors.initials: J
authors.lastname: Brooks
authors.forename: Paul
authors.initials: P
authors.lastname: Sandstrom
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Macdonald
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002460:Cell Line; D002644:Chickenpox / Q000276:immunology / Q000821:virology*; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000235:genetics / Q000502:physiology; D014645:Herpesvirus 3, Human / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008252:Macaca fascicularis; D008297:Male
chemical_list: D000914:Antibodies, Viral