title: Shared modes of protection against poxvirus infection by attenuated and conventional smallpox vaccine viruses.
abstract: The concern about bioterrorism with smallpox has raised the possibility of widespread vaccination, but the greater prevalence of immunocompromised individuals today requires a safer vaccine, and the mechanisms of protection are not well understood. Here we show that, at sufficient doses, the protection provided by both modified vaccinia Ankara and NYVAC replication-deficient vaccinia viruses, safe in immunocompromised animals, was equivalent to that of the licensed Wyeth vaccine strain against a pathogenic vaccinia virus intranasal challenge of mice. A similar variety and pattern of immune responses were involved in protection induced by modified vaccinia Ankara and Wyeth viruses. For both, antibody was essential to protect against disease, whereas neither effector CD4+ nor CD8+ T cells were necessary or sufficient. However, in the absence of antibody, T cells were necessary and sufficient for survival and recovery. Also, T cells played a greater role in control of sublethal infection in unimmunized animals. These properties, shared with the existing smallpox vaccine, provide a basis for further evaluation of these replication-deficient vaccinia viruses as safer vaccines against smallpox or against complications from vaccinia virus.
authors.affiliation: Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. belyakov@mail.nih.gov
authors.forename: Igor M
authors.initials: IM
authors.lastname: Belyakov
authors.forename: Patricia
authors.initials: P
authors.lastname: Earl
authors.forename: Amiran
authors.initials: A
authors.lastname: Dzutsev
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Kuznetsov
authors.forename: Michael
authors.initials: M
authors.lastname: Lemon
authors.forename: Linda S
authors.initials: LS
authors.lastname: Wyatt
authors.forename: James T
authors.initials: JT
authors.lastname: Snyder
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Ahlers
authors.forename: Genoveffa
authors.initials: G
authors.lastname: Franchini
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D011213:Poxviridae Infections / Q000821:virology*; D012899:Smallpox / Q000517:prevention & control*; D012900:Smallpox Vaccine; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D014612:Vaccines; D014616:Vaccinia virus / Q000502:physiology*
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D012900:Smallpox Vaccine; D014612:Vaccines; D007371:Interferon-gamma