title: Molecular smallpox vaccine delivered by alphavirus replicons elicits protective immunity in mice and non-human primates.
abstract: Naturally occurring smallpox was eradicated as a result of successful vaccination campaigns during the 1960s and 1970s. Because of its highly contagious nature and high mortality rate, smallpox has significant potential as a biological weapon. Unfortunately, the current vaccine for orthopoxviruses is contraindicated for large portions of the population. Thus, there is a need for new, safe, and effective orthopoxvirus vaccines. Alphavirus replicon vectors, derived from strains of Venezuelan equine encephalitis virus, are being used to develop alternatives to the current smallpox vaccine. Here, we demonstrated that virus-like replicon particles (VRPs) expressing the vaccinia virus A33R, B5R, A27L, and L1R genes elicited protective immunity in mice comparable to vaccination with live-vaccinia virus. Furthermore, cynomolgus macaques vaccinated with a combination of the four poxvirus VRPs (4pox-VRP) developed antibody responses to each antigen. These antibody responses were able to neutralize and inhibit the spread of both vaccinia virus and monkeypox virus. Macaques vaccinated with 4pox-VRP, flu HA VRP (negative control), or live-vaccinia virus (positive control) were challenged intravenously with 5 x 10(6)pfu of monkeypox virus 1 month after the second VRP vaccination. Four of the six negative control animals succumbed to monkeypox and the remaining two animals demonstrated either severe or grave disease. Importantly, all 10 macaques vaccinated with the 4pox-VRP vaccine survived without developing severe disease. These findings revealed that a single-boost VRP smallpox vaccine shows promise as a safe alternative to the currently licensed live-vaccinia virus smallpox vaccine.
authors.affiliation: US Army Medical Research Institute of Infectious Diseases, Virology Division, 1425 Porter Street, Fort Detrick, MD 21702, United States. jay.hooper@amedd.army.mil
authors.forename: Jay W
authors.initials: JW
authors.lastname: Hooper
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Ferro
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Golden
authors.forename: Peter
authors.initials: P
authors.lastname: Silvera
authors.forename: Jeanne
authors.initials: J
authors.lastname: Dudek
authors.forename: Kim
authors.initials: K
authors.lastname: Alterson
authors.forename: Max
authors.initials: M
authors.lastname: Custer
authors.forename: Bryan
authors.initials: B
authors.lastname: Rivers
authors.forename: John
authors.initials: J
authors.lastname: Morris
authors.forename: Gary
authors.initials: G
authors.lastname: Owens
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Smith
authors.forename: Kurt I
authors.initials: KI
authors.lastname: Kamrud
mesh_terms: D000524:Alphavirus / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D002522:Chlorocebus aethiops; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008251:Macaca; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D012900:Smallpox Vaccine / Q000235:genetics / Q000276:immunology*; D014709:Vero Cells
chemical_list: D057134:Antibodies, Neutralizing; D012900:Smallpox Vaccine