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PMID: 15047812 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Recombinant modified vaccinia virus Ankara expressing a soluble form of glycoprotein B causes durable immunity and neutralizing antibodies against multiple strains of human cytomegalovirus.

Journal of virology ·Vol. 78 ·No. 8 ·2004-04-00 ·Pages 3965-76

Wang Z, La Rosa C, Maas R, Ly H, Brewer J, Mekhoubad S, Daftarian P, Longmate J, Britt WJ, Diamond DJ

Abstract

Human cytomegalovirus (CMV) is a viral pathogen that infects both genders, who remain asymptomatic unless they receive immunosuppressive drugs or acquire infections that cause reactivation of latent virus. CMV infection also causes serious birth defects following primary maternal infection during gestation. A safe and effective vaccine to limit disease in this population continues to be elusive. A well-studied antigen is glycoprotein B (gB), which is the principal target of neutralizing antibodies (NAb) towards CMV in humans and has been implicated as the viral partner in the receptor-mediated infection by CMV in a variety of cell types. Antibody-mediated virus neutralization has been proposed as a mechanism by which host immunity could modify primary infection. Towards this goal, an attenuated poxvirus, modified vaccinia virus Ankara (MVA), has been constructed to express soluble CMV gB (gB680-MVA) to induce CMV NAb. Very high levels of gB-specific CMV NAb were produced after two doses of the viral vaccine. NAb were durable within a twofold range for up to 6 months. Neutralization titers developed in immunized mice are equivalent to titers found clinically after natural infection. This viral vaccine, expressing gB derived from CMV strain AD169, induced antibodies that neutralized CMV strains of three different genotypes. Remarkably, preexisting MVA and vaccinia virus (poxvirus) immunity did not interfere with subsequent immunizations of gB680-MVA. The safety characteristics of MVA, combined with the robust immune response to CMV gB, suggest that this approach could be rapidly translated into the clinic.

MeSH Terms
Animals Antibodies, Viral/biosynthesis Base Sequence Cytomegalovirus/genetics,immunology Cytomegalovirus Infections/immunology,prevention & control DNA, Viral/genetics Female Genotype Humans Immunoglobulin G/biosynthesis Lymphocyte Activation Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Neutralization Tests Pregnancy Solubility T-Lymphocytes/immunology T-Lymphocytes, Cytotoxic/immunology Vaccines, Attenuated/genetics,immunology Vaccines, Synthetic/genetics,immunology Vaccinia virus/genetics,immunology Viral Envelope Proteins/genetics,immunology Viral Vaccines/genetics,immunology
Chemicals
Antibodies, Viral DNA, Viral Immunoglobulin G Vaccines, Attenuated Vaccines, Synthetic Viral Envelope Proteins Viral Vaccines glycoprotein B, Simplexvirus
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Wang Zhongde
Laboratory of Vaccine Research, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA>
La Rosa Corinna
Maas Rebecca
Ly Heang
Brewer John
Mekhoubad Shahram
Daftarian Pirouz
Longmate Jeff
Britt William J
Diamond Don J
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.78.8.3965-3976.2004
Published
2004-04-00
Pages
3965-76
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC374285
Subset
IM
Grants
NCI NIH HHS · R01-CA77544 · United States
NCI NIH HHS · P01-CA30206 · United States
NCI NIH HHS · R01 CA077544 · United States
NCI NIH HHS · CA33572 · United States
NIAID NIH HHS · R01 AI049537 · United States
NIAID NIH HHS · R01 AI49537 · United States
NCI NIH HHS · P30 CA033572 · United States
NCI NIH HHS · P01 CA030206 · United States
External Links
PubMed source DOI: 10.1128/jvi.78.8.3965-3976.2004 PMC Full Text View journal details
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