Modeling a safer smallpox vaccination regimen, for human immunodeficiency virus type 1-infected patients, in immunocompromised macaques.
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.
Edghill-Smith
Yvette
Y
Laboratory of Receptor Biology and Gene Expression, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-5055, USA.
Venzon
David
D
Karpova
Tatiana
T
McNally
James
J
Nacsa
Janos
J
Tsai
Wen-Po
WP
Tryniszewska
Elzbieta
E
Moniuszko
Marcin
M
Manischewitz
Jody
J
King
Lisa R
LR
Snodgrass
Steven J
SJ
Parrish
John
J
Markham
Phil
P
Sowers
Marsha
M
Martin
Derrick
D
Lewis
Mark G
MG
Berzofsky
Jay A
JA
Belyakov
Igor M
IM
Moss
Bernard
B
Tartaglia
Jim
J
Bray
Mike
M
Hirsch
Vanessa
V
Golding
Hana
H
Franchini
Genoveffa
G
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
D000914:Antibodies, Viral; C078786:DryVax vaccine; C078787:NYVAC vaccine; D012900:Smallpox Vaccine; D014613:Vaccines, Attenuated; D014765:Viral Vaccines