Intrauterine Transmission of Cytomegalovirus to Infants of Women With Preconceptional Immunity

Boppana, Suresh B.; Rivera, Lisa B.; Fowler, Karen B.; Mach, Michael; Britt, William J.

doi:10.1097/00006254-200110000-00011

Cited by 99 publications

(142 citation statements)

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“…Therefore, the expression of the gp100 gene was also controlled by the MCMV P 1/3 -E-P 2 promoter. In addition, we modified the CD8 epitope contained in the gp100 protein (gp100 [25][26][27][28][29][30][31][32][33]. It was previously shown that an altered gp100 [25][26][27][28][29][30][31][32][33] (KGPRNQDWL) epitope binds to MHC class I molecule H-2D b with greater affinity than the original gp100 [25][26][27][28][29][30][31][32][33] The data shown are representative of two independent experiments.…”

Section: Construction and Characterization Of Recombinant Mcmv-gp100 mentioning

confidence: 99%

“…CMV belongs to the Herpesviridae family, and the following unique characteristics make CMV a promising cancer vaccine vector: (i) CMV establishes a lifelong, asymptomatic infection in immunocompetent hosts; (ii) a remarkable characteristic of CMV infections is that a robust superinfection is observed despite the presence of preexisting CMV-specific immunity, and thus individuals who may already harbor latent CMV can be reimmunized with CMV-based vaccines (23)(24)(25); (iii) cloning of the CMV genome as a bacterial artificial chromosome makes it possible to introduce multiple tumor antigens into the CMV vector; (iv) CMV infection induces a strong inflammatory innate immune response followed by a robust polyfunctional CD8 T-cell expansion, which makes CMV a potentially ideal T-cell-based cancer vaccine vector; (v) in mice and in humans, a process called memory inflation continues long after the establishment of latency, in which CMV-specific CD8 T-cell populations proliferate for the life of the host (26)(27)(28)(29), and a large percentage of these "inflationary" CD8 T cells are functional as exhibited by their ability to secrete multiple cytokines; and (vi) the CMV-specific CD8 þ T cells are distributed widely in lymphoid and nonlymphoid organs, such as the lung, liver, and brain; therefore, CMV vaccines could be used to target metastases in different organs.…”

Section: Introductionmentioning

confidence: 99%

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Cytomegalovirus-Based Vaccine Expressing a Modified Tumor Antigen Induces Potent Tumor-Specific CD8+ T-cell Response and Protects Mice from Melanoma

Qiu

Huang

Grenier

et al. 2015

Cancer Immunology Research

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The presence of tumor-infiltrating CD8 þ T cells is associated with tumor regression and better prognosis. Cytomegalovirus (CMV) infection elicits a robust and long-lasting CD8 þ T-cell response, which makes CMV a potentially promising vaccine vector against cancer. In the current study, we used recombinant murine CMV (MCMV) strains as prophylactic and therapeutic vaccines in an aggressive B16 lung metastatic melanoma model. Immunization with MCMV-expressing ovalbumin (OVA) induced a potent OVA-specific CD8 þ T-cell response and was effective in protecting mice from OVAexpressing B16 melanoma in an antigen-dependent manner. We engineered MCMV to express a modified B16 melanoma antigen gp100 (MCMV-gp100KGP). Immunization with MCMV-gp100KGP was highly effective in overcoming immune tolerance to self-antigen and induced a strong, long-lasting gp100-specific CD8 þ T-cell response even in the presence of preexisting anti-CMV immunity. Furthermore, both prophylactic and therapeutic vaccinations of mice with MCMV-gp100KGP effectively protected mice from highly aggressive lung B16-F10 melanoma, and the protection was mediated by gp100-specific CD8 þ T cells. We showed that MCMV is a superior vaccine vector compared with a commonly used vesicular stomatitis virus vector. Collectively, our studies demonstrate that CMV is a promising vaccine vector to prevent and treat tumors.

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Section: Construction and Characterization Of Recombinant Mcmv-gp100 mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cytomegalovirus-Based Vaccine Expressing a Modified Tumor Antigen Induces Potent Tumor-Specific CD8+ T-cell Response and Protects Mice from Melanoma

Qiu

Huang

Grenier

et al. 2015

Cancer Immunology Research

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“…Most of these cases are from primary infections in the mother, but congenital CMV infection has now been identiWed in mothers who were immune before their pregnancies. Some have developed neurosensory hearing loss [17].…”

Section: Congenital CMV Infection (Cid)mentioning

confidence: 99%

“…This was the Wrst indication of strain diVerences among CMV isolates. More recently, Boppana et al [17] studied maternal serum with preconceptual immunity against CMV before and after conception of an infant with congenital CMV infection; ten of the 16 mothers with congenitally infected children acquired new antibody speciWcities against glycoprotein H (gH). This protein is part of the armamentarium of neutralizing antibodies.…”

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confidence: 99%

The history of cytomegalovirus and its diseases

2007

Med Microbiol Immunol

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Intranuclear inclusions typical of cytomegalovirus infections were Wrst noticed in 1881 by German scientists who thought they represented protozoa. After viruses were grown in cell cultures, Weller, Smith and Rowe independently isolated and grew CMV from man and mice in [1956][1957]. Antibodies in 30-100% of normal adults indicate not only a past infection, but the presence of a present latent infection. The presence of CMV DNA in tissues and most organs surveyed indicates the ubiquity of latent infection. CMV disease requires the virus and some deWciency of immunity such as occurs in the immature fetus, in AIDS, and in transplant patients on immunosuppressive drugs. Antiviral agents can inhibit CMV replication but they cannot prevent or cure latent infections. A pharmacological approach using the many leads in understanding latency is needed. Keywords Antiviral therapy · CMV in AIDS · CMV after transplantation · Discovery of CMV · Epidemiology of CMV · Latent infection by CMV Discovery of cytomegalovirusRibbert [1] wrote that in 1881, he saw large cells in sections of the kidney of a luetic stillborn and in the parotid gland of children which he was unable to interpret until he saw the report of Jesionek and Kiolemenoglou ( Von Glahn and Pappenheimer [4] noted that Lipschuetz [5] had discovered intranuclear inclusion containing cells in lesions in man infected by herpes zoster and herpes genitalis. Thus they believed such abnormal cells were produced by viruses, and they doubted that they were related to protozoa. This was the Wrst indication that cells with intranuclear inclusions might be related to a group of related viruses, now known as the herpesviridae.Farber and Wolbach [6] found such inclusion bearing cells in the salivary glands of 26 out of 183 children examined after death from diverse causes. This was the Wrst approximation of the fact that infection by cytomegalovirus is highly frequent.By 1932, 25 cases of a rare lethal congenial infection characterized by petechiae, hepatosplenomegaly, and intracerebral calciWcation had been described. All of them had cells with typical intranuclear inclusions. Wyatt et al. [7] suggested the name, "generalized cytomegalic inclusion disease (CID)", although its viral etiology was not yet known. A uniform site of involvement were cells of the renal tubules. They suggested that the disease might be diagnosed during life by searching for cells with inclusions in urinary sediments.Following this clue, Fetterman [8] made a cytological preparation from the urine sediment of a suspected case, and made the Wrst intravitum diagnosis of CID.Minder [9] Wrst saw by electronmicroscopy 199 nm particles, suggestive of a virus, in the clear halo around the intranuclear inclusion of pancreatic cells in a case of CID.

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“…In contrast, only 1%-2% of CMVseroimmune women, in whom the virus is persistent, will transmit the virus to their fetus. Moreover, infants born to CMV-seropositive women are less likely to exhibit signs of CMV infection at birth and typically develop only mild neurological sequelae, most commonly sensorineural hearing loss [9,10].…”

mentioning

confidence: 99%

Maternal Antibody Responses and Nonprimary Congenital Cytomegalovirus Infection of HIV-1–Exposed Infants

et al. 2016

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Risk of congenital cytomegalovirus (cCMV) transmission is highly dependent on the presence of preexisting maternal immunity, with the lowest rates observed in CMV-seroimmune populations. Among infants of CMV-seroimmune women, those who are exposed to human immunodeficiency virus (HIV) have an increased risk of acquiring cCMV infection as compared to HIV-unexposed infants. To better understand the risk factors of nonprimary cCMV transmission in HIV-infected women, we performed a casecontrol study in which CMV-specific plasma antibody responses from 19 CMV-transmitting and 57 CMV-nontransmitting women with chronic CMV/HIV coinfection were evaluated for the ability to predict the risk of cCMV infection. Primary multivariable conditional logistic regression analysis revealed an association between epithelial-tropic CMV neutralizing titers and a reduced risk of cCMV transmission (odds ratio [OR], 0.18; 95% confidence interval [CI], .03-.93; P = .04), although this effect was not significant following correction for multiple comparisons (false-discovery rate, 0.12). Exploratory analysis of the CMV specificity of plasma antibodies revealed that immunoglobulin G (IgG) responses against the glycoprotein B (gB) neutralizing epitope AD-2 had a borderline association with low risk of transmission (OR, 0.72; 95% CI, .51-1.00; P = .05), although this was not confirmed in a post hoc plasma anti-AD-2 IgG blocking assay. Our data suggest that maternal neutralizing antibody responses may play a role in protection against cCMV in HIV/CMV-coinfected populations.

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Intrauterine Transmission of Cytomegalovirus to Infants of Women With Preconceptional Immunity

Cited by 99 publications

References 0 publications

Cytomegalovirus-Based Vaccine Expressing a Modified Tumor Antigen Induces Potent Tumor-Specific CD8+ T-cell Response and Protects Mice from Melanoma

Cytomegalovirus-Based Vaccine Expressing a Modified Tumor Antigen Induces Potent Tumor-Specific CD8+ T-cell Response and Protects Mice from Melanoma

The history of cytomegalovirus and its diseases

Maternal Antibody Responses and Nonprimary Congenital Cytomegalovirus Infection of HIV-1–Exposed Infants

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