title: Rapid protection in a monkeypox model by a single injection of a replication-deficient vaccinia virus.
abstract: The success of the World Health Organization smallpox eradication program three decades ago resulted in termination of routine vaccination and consequent decline in population immunity. Despite concerns regarding the reintroduction of smallpox, there is little enthusiasm for large-scale redeployment of licensed live vaccinia virus vaccines because of medical contraindications and anticipated serious side effects. Therefore, highly attenuated strains such as modified vaccinia virus Ankara (MVA) are under evaluation in humans and animal models. Previous studies showed that priming and boosting with MVA provided protection for >2 years in a monkeypox virus challenge model. If variola virus were used as a biological weapon, however, the ability of a vaccine to quickly induce immunity would be essential. Here, we demonstrate more rapid immune responses after a single vaccination with MVA compared to the licensed Dryvax vaccine. To determine the kinetics of protection of the two vaccines, macaques were challenged intravenously with monkeypox virus at 4, 6, 10, and 30 days after immunization. At 6 or more days after vaccination with MVA or Dryvax, the monkeys were clinically protected (except for 1 of 16 animals vaccinated with MVA), although viral loads and number of skin lesions were generally higher in the MVA vaccinated group. With only 4 days between immunization and intravenous challenge, however, MVA still protected whereas Dryvax failed. Protection correlated with the more rapid immune response to MVA compared to Dryvax, which may be related to the higher dose of MVA that can be tolerated safely.
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-3210, USA.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Earl
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Americo
authors.forename: Linda S
authors.initials: LS
authors.lastname: Wyatt
authors.forename: Ondraya
authors.initials: O
authors.lastname: Espenshade
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Bassler
authors.forename: Kathy
authors.initials: K
authors.lastname: Gong
authors.forename: Shuling
authors.initials: S
authors.lastname: Lin
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Peters
authors.forename: Lowrey
authors.initials: L
authors.lastname: Rhodes
authors.forename: Yvette Edghill
authors.initials: YE
authors.lastname: Spano
authors.forename: Peter M
authors.initials: PM
authors.lastname: Silvera
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D008252:Macaca fascicularis; D008993:Monkeypox virus / Q000276:immunology*; D009500:Neutralization Tests; D012899:Smallpox / Q000517:prevention & control*; D012900:Smallpox Vaccine / Q000008:administration & dosage / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology*; D014779:Virus Replication / Q000502:physiology
chemical_list: D016207:Cytokines; C078786:DryVax vaccine; D012900:Smallpox Vaccine; D014613:Vaccines, Attenuated