Estimated susceptibility to asymptomatic secondary immune response against measles in late convalescent and vaccinated persons

Damien, Benjamin; Huiss, S.; Schneider, François; Muller, Claude P.

doi:10.1002/(sici)1096-9071(199809)56:1<85::aid-jmv14>3.0.co;2-v

Cited by 39 publications

(14 citation statements)

References 18 publications

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“…However, considerable evidence suggests that this may not be the case given that asymptomatic measles virus infection has been well documented in vaccinated children. 27 Recently, it was demonstrated that macaques vaccinated with live attenuated virus or DNA can experience subclinical infection when challenged with measles virus. 28 Studies have shown that the therapeutic efficacy of conditionally replicating adenoviruses, 29 herpesviruses, 30 or reoviruses 4 was not negated by pre-existing antiviral antibodies.…”

Section: Discussionmentioning

confidence: 99%

Systemic therapy of myeloma xenografts by an attenuated measles virus

Peng¹,

Ahmann²,

Pham³

et al. 2001

Blood

167

157

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IntroductionAttenuated viruses with tumor specificity have attracted considerable interest as novel anticancer agents, and clinical testing of several such agents is under way. 1 Tumor selectivity of these viruses has been attributed to various intracellular restrictions to their life cycles that are strongly inhibitory to virus propagation in nontransformed cells but that are overridden by cellular factors present in neoplastic cells. [2][3][4][5][6] Measles is an acute viral disease caused by a negative-strand RNA virus of the family Paramyxoviridae, which remains responsible for approximately 1 million deaths each year. 7 In the early stages of measles virus (MV) infection, the lymphoid organs and tissues are predominant sites for viral replication, leading to the formation of giant reticuloendothelial (Warthin-Finkeldey) cells in the tissues. 7 Measles is prevented by the use of a live attenuated virus vaccine now routinely administered during childhood. The Edmonston-B vaccine strain of measles virus (MV-Edm) was attenuated by serial tissue culture passage of a clinical isolate. 7 Despite its profound attenuation as a human pathogen, MV-Edm replicates more efficiently than nonattenuated measles virus in many primate cell lines, inducing cell cell fusion and the formation of characteristic multinucleated syncytia. 8 Here, we compared the ability of MV-Edm to replicate in neoplastic myeloma cells and normal cells, and we investigated its potential as an antitumor agent in human myeloma xenografts in vivo. We report that the virus replicated selectively in a panel of 6 myeloma cell lines and in CD138-sorted myeloma cells from 6 patients and that it caused potent cytopathic effects. When administered intratumorally or intravenously into mice bearing established myeloma xenografts, MV-Edm caused growth inhibition or total regression of 2 different myeloma xenograft models. Materials and methods Cell cultureThe multiple myeloma ARH-77 cell line (ATCC CRL-1621) was obtained from American Type Culture Collection (Rockville, MD). The rest of the multiple myeloma cell lines were kind gifts of Dr John Lust (RPMI 8226), Dr Diane Jelinek (KAS-6/1), and Dr Rafael Fonseca (KMS-11, MM1, JJN-3) from the Mayo Clinic (Rochester, MN). All the human myeloma cell lines were maintained in RPMI-1640 (Gibco BRL, Rockville, MD) supplemented with 10% fetal bovine serum (FBS) except for KAS-6/1, which was grown in media supplemented with 1 ng/mL interleukin (IL)-6 (Sigma, St Louis, MO). Bone marrow aspirates were obtained after institutional review board approval and informed patient consent. Bone marrow samples were drawn into a tube containing heparin and centrifuged on a Ficoll-Hypaque gradient (Amersham Pharmacia, Piscataway, NJ) to enrich for mononuclear cells. Mononuclear cells were then incubated with MACS CD138 microbeads (Miltenyi Biotech, Auburn, CA) for 15 minutes in a 8°C water bath. CD138 ϩ primary myeloma cells were then isolated, washed, and maintained in 10% FBS-RPMI supplemented with 1 ng/mL IL-6. Peripheral blood lym...

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Section: Discussionmentioning

confidence: 99%

Systemic therapy of myeloma xenografts by an attenuated measles virus

Peng¹,

Ahmann²,

Pham³

et al. 2001

Blood

167

157

View full text Add to dashboard Cite

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“…There is evidence to suggest that this may not be the case, since examination of the immune response of convalescent children suggested that MV infection can occur after vaccination without resulting in disease (15). Moreover, it was recently shown that macaques vaccinated with live attenuated virus or DNA can experience a subclinical infection at challenge (40).…”

Section: Discussionmentioning

confidence: 99%

Recombinant Measles Viruses Efficiently Entering Cells through Targeted Receptors

Schneider

Bullough²,

Vongpunsawad

et al. 2000

J Virol

103

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We sought proof of principle that one of the safest human vaccines, measles virus Edmonston B (MV-Edm), can be genetically modified to allow entry via cell surface molecules other than its receptor CD46. Hybrid proteins consisting of the epidermal growth factor (EGF) or the insulin-like growth factor 1 (IGF1) linked to the extracellular (carboxyl) terminus of the MV-Edm attachment protein hemagglutinin (H) were produced. The standard H protein gene was replaced by one coding for H/EGF or H/IGF1 in cDNA copies of the MV genome. Recombinant viruses were rescued and replicated to titers approaching those of the parental strain. MV displaying EGF or IGF1 efficiently entered CD46-negative rodent cells expressing the human EGF or the IGF1 receptor, respectively, and the EGF virus caused extensive syncytium formation and cell death. Taking advantage of a factor Xa protease recognition site engineered in the hybrid H proteins, the displayed domain was cleaved off from virus particles, and specific entry in rodent cells was abrogated. These studies prove that MV can be engineered to selectively eliminate cells expressing a targeted receptor and provide insights into the mechanism of MV entry.Measles virus (MV) is a nonsegmented negative-strand RNA virus of the family Paramyxoviridae, genus Morbillivirus. It remains one of the leading causes of infant death in developing countries, but live attenuated vaccines derived from the MV strain Edmonston B (MV-Edm) have almost completely eliminated measles-related fatalities in countries that have adopted compulsory vaccination (13). We aim to transform MV-Edm, an extremely cost-effective public health tool, into a replicating vector for cytoreductive therapy. Restriction of cell entry through the use of receptor-specific virus attachment is the approach that we are developing to achieve selective MV replication in target cells. To this end, we describe here the production of dual tropic MV-Edm derivatives that specifically enter rodent cells through a targeted receptor.The MV envelope is composed of two glycoproteins: the hemagglutinin (H) and the fusion (F) protein. The H protein binds directly to the cellular receptor (17), and the F protein, containing a putative hydrophobic fusion peptide, executes fusion between the viral and the cell membrane at a neutral pH (50). A cellular receptor for MV-Edm is the type I glycoprotein CD46 (18, 34), a ubiquitous regulator of complement activation expressed in humans and Old World monkeys. CD46 is a major determinant of virus tropism, and its expression allows MV binding, entry, and replication in normally nonsusceptible rodent cells (6,18,33). The CD46 extracellular part consists of four complement control protein domains (CCP) and other small repeats (30). The viral H protein binds initially the two most distal domains, CCP 1 and 2 (6, 32), followed by secondary contacts with CCP 4 (12, 16). Several CCP 1 and 2 amino acids important for virus binding have been identified (5,22), and the crystal structure of these domains (8) reveals an...

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“…We know, for example, that the sera of convalescent measles patients or of those who have been vaccinated variably neutralize the wild virus strains [4] but, conversely, the neutralizing capacity of the polyclonal response of B-cells, whether induced by infection or by vaccination, is not affected or influenced by the genotype [5]. So did this strain have an increased virulence, giving it a selective advantage, e.g.…”

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confidence: 99%