Modeling a safer smallpox vaccination regimen, for human immunodeficiency virus type 1-infected patients, in immunocompromised Macaques

被引：26

作者：

Edghill-Smith, Y

Venzon, D

Karpova, T

McNally, J

Nacsa, J

Tsai, WP

Tryniszewska, E

Moniuszko, M

Manischewitz, J

King, LR

Snodgrass, SJ

Parrish, J

Markham, P

Sowers, M

Martin, D

Lewis, MG

Berzofsky, JA

Belyakov, IM

Moss, B

Tartaglia, J

Bray, M

Hirsch, V

Golding, H

Franchini, G

机构：

[1] NCI, Basic Res Lab, Bethesda, MD 20892 USA

[2] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA

[3] NCI, Fluorescence Imaging Facil, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA

[4] NCI, Metab Branch, Bethesda, MD 20892 USA

[5] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA

[6] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA

[7] NIAID, Biodef Clin Res Branch, Off Clin Res, Bethesda, MD 20892 USA

[8] NIAID, Mol Microbiol Lab, Rockville, MD USA

[9] NIAID, Bioqual, Rockville, MD USA

[10] Adv BioSci Labs, Kensington, NSW, Australia

[11] So Res Inst, Frederick, MD USA

[12] Med Acad Bialystok, Dept Pediat 3, Bialystok, Waszyngtona, Poland

[13] Aventis Pasteur, Toronto, ON, Canada

来源：

JOURNAL OF INFECTIOUS DISEASES | 2003年 / 188卷 / 08期

关键词：

D O I：

10.1086/378518

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：1181 / 1191

页数：11