Smallpox vaccine does not protect macaques with AIDS from a lethal monkeypox virus challenge.
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.
Edghill-Smith
Yvette
Y
Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, Maryland 20892, USA.
Bray
Mike
M
Whitehouse
Chris A
CA
Miller
David
D
Mucker
Eric
E
Manischewitz
Jody
J
King
Lisa R
LR
Robert-Guroff
Marjorie
M
Hryniewicz
Anna
A
Venzon
David
D
Meseda
Clement
C
Weir
Jerry
J
Nalca
Aysegul
A
Livingston
Virginia
V
Wells
Jay
J
Lewis
Mark G
MG
Huggins
John
J
Zwiers
Susan H
SH
Golding
Hana
H
Franchini
Genoveffa
G
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
D000914:Antibodies, Viral; C078786:DryVax vaccine; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012900:Smallpox Vaccine; D014613:Vaccines, Attenuated