Recent Approaches and Strategies in the Generation of Anti-human Cytomegalovirus Vaccines

Boppana, Suresh B.; Britt, William J.

doi:10.1007/978-1-0716-1111-1_19

Cited by 14 publications

(18 citation statements)

References 391 publications

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“…Virus-like particles consisting of a fusion product of extracellular domain glycoprotein B and vesicular stomatitis virus G-protein induced high titres of neutralizing antibodies[ 81 ]. Live-attenuated vaccine has shown a good safety profile, inducing both humoural and cell-mediated immunity, and reducing the incidence of severe infection[ 82 , 83 ]. However, vaccines still fail to prevent infection in seronegative solid organ transplant recipients.…”

Section: Preventionmentioning

confidence: 99%

Cytomegalovirus infection in liver-transplanted children

Onpoaree¹,

Sanpavat²,

Sintusek³

2022

WJH

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Cytomegalovirus (CMV) infection is a common complication of liver trans-plantation in children. The CMV serostatus of recipients and donors is the primary risk factor, and prophylaxis or pre-emptive strategies are recommended for high-risk patients. Graft rejection, coinfection and Epstein-Bar virus reactivation, which can lead to post-transplant lymphoproliferative disease, are indirect effects of CMV infection. Assessment of CMV infection viral load should be routinely performed upon clinical suspicion. However, tissue-invasive CMV disease is not associated with CMV viraemia and requires confirmation by tissue pathology. Oral valganciclovir and intravenous ganciclovir are equivalent treatments, and the duration of treatment depends on factors including CMV viral load, tissue pathology, and clinical response. Risk stratification by donor and recipient status prior to transplantation and post-transplantation antiviral prophylaxis or pre-emptive therapy are recommended. Adult guidelines have been established but additional study of the effectiveness of the preventive guidelines in children is needed. This review summarizes the burden, risk factors, clinical manifestations, laboratory evaluation, treatment, and prevention of CMV infection in children after liver transplantation.

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Section: Preventionmentioning

confidence: 99%

Cytomegalovirus infection in liver-transplanted children

Onpoaree¹,

Sanpavat²,

Sintusek³

2022

WJH

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“…HCMV is the most common member of the beta‐herpesvirus family, infecting the majority of the human population worldwide. HCMV infects a wide range of cell types, and although primary infection is usually asymptomatic, HCMV is an opportunistic pathogen in immunocompromised adults and the leading cause of congenital infections worldwide 2 . The primary targets of HHV6A and 6B and HHV7 are activated T cells, and primary infection with these viruses at infancy causes roseola or sixth disease 3 …”

Section: Introduction To Herpesvirusesmentioning

confidence: 99%

“…HCMV infects a wide range of cell types, and although primary infection is usually asymptomatic, HCMV is an opportunistic pathogen in immunocompromised adults and the leading cause of congenital infections worldwide. 2 The primary targets of HHV6A and 6B and HHV7 are activated T cells, and primary infection with these viruses at infancy causes roseola or sixth disease. 3 The gamma-herpesviruses subfamily includes Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV).…”

Section: Introduction To Herpesvirusesmentioning

confidence: 99%

“…HCMV reactivation from latency is a major clinical concern in immunocompromised individuals after hematopoietic cell or solid organ transplant, where HCMV can cause graft failure or spread to host organs. 2 There are currently no licensed vaccines for HCMV, and antiviral therapies, such as ganciclovir, are only available to treat productive HCMV infection; these therapies, however, have severe side effects and resistance often develops. The strict species specificity of HCMV poses major challenges for researching and understanding its pathogenesis.…”

Section: Introduction To Herpesvirusesmentioning

confidence: 99%

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Rethinking human cytomegalovirus latency reservoir

Schwartz

Stern-Ginossar

2023

Annals of the New York Academy of Sciences

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Human cytomegalovirus (HCMV) is a prevalent herpesvirus, infecting the majority of the human population. Like other herpesviruses, it causes lifelong infection through the establishment of latency. Although reactivation from latency can cause significant morbidity and mortality in immunocompromised hosts, our understanding of HCMV latency and how it is maintained remains limited. Here, we discuss the characterized latency reservoir in hematopoietic cells in the bone marrow and the gaps in our knowledge of mechanisms that facilitate HCMV genome maintenance in dividing cells. We further review clinical evidence that strongly suggests the tissue origin of HCMV reactivation, and we outline similarities to murine cytomegalovirus where latency in tissue‐resident cells has been demonstrated. Overall, we think these observations call for a rethinking of HCMV latency reservoirs and point to potential sources of HCMV latency that reside in tissues.

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“…The clinical relevance of human cytomegalovirus (hCMV), the prototype member of the βsubfamily of the herpes virus family [1], results from severe and often lethal CMV disease that it causes under conditions of compromised immunity [2][3][4]. A concern with significant health system impact are birth defects resulting from congenital infection of immunologically immature fetuses, a syndrome historically known as cytomegalic inclusion disease (CID) (for overviews, see [5,6]).…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy of cytomegalovirus infection by low-dose adoptive transfer of antiviral CD8 T cells relies on substantial post-transfer expansion of central memory cells but not effector-memory cells

Holtappels,

Becker,

Hamdan

et al. 2023

Preprint

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Cytomegaloviruses (CMVs) are host species-specific in their replication. It is a hallmark of all CMVs that productive primary infection is controlled by concerted innate and adaptive immune responses in the immunocompetent host. As a result, the infection usually passes without overt clinical symptoms and develops into latent infection, referred to as ’latency’. During latency, the virus is maintained in a non-replicative state from which it can reactivate to productive infection under conditions of waning immune surveillance. In contrast, infection of an immunocompromised host causes CMV disease with viral multiple-organ histopathology resulting in organ failure. Primary or reactivated CMV infection of hematopoietic cell transplantation (HCT) recipients in a “window of risk” between therapeutic hematoablative leukemia therapy and immune system reconstitution remains a clinical challenge. Studies in the mouse model of experimental HCT and infection with murine CMV (mCMV), followed by clinical trials in HCT patients with human CMV (hCMV) reactivation, have revealed a protective function of virus-specific CD8 T cells upon adoptive cell transfer (AT). Memory CD8 T cells derived from latently infected hosts are a favored source for immunotherapy by AT. Strikingly low numbers of these cells were found to prevent CMV disease, suggesting either an immediate effector function of few transferred cells or a clonal expansion generating high numbers of effector cells. In the murine model, the memory population consists of resting central memory T cells (TCM), as well as of conventional effector-memory T cells (cTEM) and inflationary effector-memory T cells (iTEM). iTEM, increase in numbers over time in the latently infected host, a phenomenon known as ‘memory inflation’ (MI). They thus appeared to be a promising source for use in immunotherapy. However, we show here that iTEM contribute little to the control of infection after AT, which rests almost exclusively on a superior proliferation potential of TCM.

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Recent Approaches and Strategies in the Generation of Anti-human Cytomegalovirus Vaccines

Cited by 14 publications

References 391 publications

Cytomegalovirus infection in liver-transplanted children

Cytomegalovirus infection in liver-transplanted children

Rethinking human cytomegalovirus latency reservoir

Immunotherapy of cytomegalovirus infection by low-dose adoptive transfer of antiviral CD8 T cells relies on substantial post-transfer expansion of central memory cells but not effector-memory cells

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