title: Modeling a safer smallpox vaccination regimen, for human immunodeficiency virus type 1-infected patients, in immunocompromised macaques.
abstract: We have modeled smallpox vaccination with Dryvax (Wyeth) in rhesus macaques that had depletion of CD4(+) T cells induced by infection with simian immunodeficiency virus or simian/human immunodeficiency virus. Smallpox vaccination induced significantly larger skin lesions in immunocompromised macaques than in healthy macaques. Unexpectedly, "progressive vaccinia" was infrequent. Vaccination of immunocompromised macaques with the genetically-engineered, replication-deficient poxvirus NYVAC, before or after retrovirus infection, was safe and lessened the severity of Dryvax-induced skin lesions. Neutralizing antibodies to vaccinia were induced by NYVAC, even in macaques with severe CD4(+) T cell depletion, and their titers inversely correlated with the time to complete resolution of the skin lesions. Together, these results provide the proof of concept, in macaque models that mirror human immunodeficiency virus type 1 infection, that a prime-boost approach with a highly attenuated poxvirus followed by Dryvax increases the safety of smallpox vaccination, and they highlight the importance of neutralizing antibodies in protection against virulent poxvirus.
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-5055, USA.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Edghill-Smith
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: Tatiana
authors.initials: T
authors.lastname: Karpova
authors.forename: James
authors.initials: J
authors.lastname: McNally
authors.forename: Janos
authors.initials: J
authors.lastname: Nacsa
authors.forename: Wen-Po
authors.initials: WP
authors.lastname: Tsai
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Tryniszewska
authors.forename: Marcin
authors.initials: M
authors.lastname: Moniuszko
authors.forename: Jody
authors.initials: J
authors.lastname: Manischewitz
authors.forename: Lisa R
authors.initials: LR
authors.lastname: King
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Snodgrass
authors.forename: John
authors.initials: J
authors.lastname: Parrish
authors.forename: Phil
authors.initials: P
authors.lastname: Markham
authors.forename: Marsha
authors.initials: M
authors.lastname: Sowers
authors.forename: Derrick
authors.initials: D
authors.lastname: Martin
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
authors.forename: Igor M
authors.initials: IM
authors.lastname: Belyakov
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
authors.forename: Jim
authors.initials: J
authors.lastname: Tartaglia
authors.forename: Mike
authors.initials: M
authors.lastname: Bray
authors.forename: Vanessa
authors.initials: V
authors.lastname: Hirsch
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; D004195:Disease Models, Animal; D015658:HIV Infections / Q000150:complications*; D015497:HIV-1; D006801:Humans; D007115:Immunization Schedule; D016867:Immunocompromised Host; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications; D015302:Simian Immunodeficiency Virus; D012867:Skin / Q000473:pathology; D012899:Smallpox / Q000517:prevention & control*; D012900:Smallpox Vaccine / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; C078786:DryVax vaccine; C078787:NYVAC vaccine; D012900:Smallpox Vaccine; D014613:Vaccines, Attenuated; D014765:Viral Vaccines