title: Smallpox vaccine does not protect macaques with AIDS from a lethal monkeypox virus challenge.
abstract: It is unknown whether smallpox vaccination would protect human immunodeficiency virus type 1 (HIV-1)-infected individuals, because helper CD4(+) cells, the targets of HIV-1 infection, are necessary for the induction of both adaptive CD8(+) cell and B cell responses. We have addressed this question in macaques and have demonstrated that, although smallpox vaccination is safe in immunodeficient macaques when it is preceded by immunization with highly attenuated vaccinia strains, the macaques were not protected against lethal monkeypox virus challenge if their CD4(+) cell count was <300 cells/mm(3). The lack of protection appeared to be associated with a defect in vaccinia-specific immunoglobulin (Ig) switching from IgM to IgG. Thus, vaccination strategies that bypass CD4(+) cell help are needed to elicit IgG antibodies with high affinity and adequate tissue distribution and to restore protection against smallpox in severely immunocompromised individuals.
authors.affiliation: Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Edghill-Smith
authors.forename: Mike
authors.initials: M
authors.lastname: Bray
authors.forename: Chris A
authors.initials: CA
authors.lastname: Whitehouse
authors.forename: David
authors.initials: D
authors.lastname: Miller
authors.forename: Eric
authors.initials: E
authors.lastname: Mucker
authors.forename: Jody
authors.initials: J
authors.lastname: Manischewitz
authors.forename: Lisa R
authors.initials: LR
authors.lastname: King
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
authors.forename: Anna
authors.initials: A
authors.lastname: Hryniewicz
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: Clement
authors.initials: C
authors.lastname: Meseda
authors.forename: Jerry
authors.initials: J
authors.lastname: Weir
authors.forename: Aysegul
authors.initials: A
authors.lastname: Nalca
authors.forename: Virginia
authors.initials: V
authors.lastname: Livingston
authors.forename: Jay
authors.initials: J
authors.lastname: Wells
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: John
authors.initials: J
authors.lastname: Huggins
authors.forename: Susan H
authors.initials: SH
authors.lastname: Zwiers
authors.forename: Hana
authors.initials: H
authors.lastname: Golding
authors.forename: Genoveffa
authors.initials: G
authors.lastname: Franchini
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D018791:CD4 Lymphocyte Count; D016867:Immunocompromised Host; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D008253:Macaca mulatta; D045908:Mpox, Monkeypox / Q000401:mortality* / Q000517:prevention & control*; D008993:Monkeypox virus / Q000472:pathogenicity*; D009500:Neutralization Tests; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000401:mortality* / Q000821:virology; D012900:Smallpox Vaccine / Q000008:administration & dosage* / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; C078786:DryVax vaccine; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012900:Smallpox Vaccine; D014613:Vaccines, Attenuated