Congenital Human Cytomegalovirus Infection and the Enigma of Maternal Immunity

Britt, William J.

doi:10.1128/jvi.02392-16

Cited by 153 publications

(176 citation statements)

References 44 publications

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“…Therefore, the ideal situation would be to control the virus before reaching the brain and inducing inflammatory response. It is well established that even seropositivity in pregnant women does not guarantee protection against congenital HCMV infection, implying the need for vaccines which would induce more efficient humoral and cellular immunity, and prevent fetal infection or at least prevent virus to reach the brain undergoing development (Britt, 2017). There is significant development in this field, especially after the identification of a pentameric complex that seems to be essential target for vaccination (Plotkin, 2015, Macagno et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Brain‐resident memory CD8⁺ T cells induced by congenital CMV infection prevent brain pathology and virus reactivation

et al. 2018

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Congenital HCMV infection is a leading infectious cause of long-term neurodevelopmental sequelae. Infection of newborn mice with mouse cytomegalovirus (MCMV) intraperitoneally is a well-established model of congenital human cytomegalovirus infection, which best recapitulates the hematogenous route of virus spread to brain and subsequent pathology. Here, we used this model to investigate the role, dynamics, and phenotype of CD8 T cells in the brain following infection of newborn mice. We show that CD8 T cells infiltrate the brain and form a pool of tissue-resident memory T cells (T cells) that persist for lifetime. Adoptively transferred virus-specific CD8 T cells provide protection against primary MCMV infection in newborn mice, reduce brain pathology, and remain in the brain as T cells. Brain CD8 T cells were long-lived, slowly proliferating cells able to respond to local challenge infection. Importantly, brain CD8 T cells controlled latent MCMV and their depletion resulted in virus reactivation and enhanced inflammation in brain.

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Section: Discussionmentioning

confidence: 99%

Brain‐resident memory CD8⁺ T cells induced by congenital CMV infection prevent brain pathology and virus reactivation

et al. 2018

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“…Some researchers have argued that conventional immune metrics currently used as a surrogate marker of effective anti-HCMV immunity, such as neutralization, may not tell the whole story (72). This in-depth investigation of the immune responses elicited by the most efficacious HCMV vaccine candidate to-date has revealed important biology of antibody functions that are potentially-protective against HCMV infection.…”

Section: Discussionmentioning

confidence: 99%

HCMV glycoprotein B subunit vaccine efficacy was mediated by non-neutralizing antibody effector functions

Nelson

Huffman

Rosa

et al. 2018

Preprint

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word count: 242 (250 max) 24Significance word count: 120 (120 max) 25Manuscript character count: 48,559 (49,000 max) 26 peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/246884 doi: bioRxiv preprint first posted online 2 Abstract: 27Human cytomegalovirus (HCMV) is the most common congenital infection worldwide, frequently 28 causing hearing loss and brain damage in afflicted infants. A vaccine to prevent maternal 29 acquisition of HCMV during pregnancy is necessary to reduce the incidence of infant disease. 30The glycoprotein B (gB) + MF59 adjuvant subunit vaccine platform is the most successful 31HCMV vaccine tested to-date, demonstrating approximately 50% efficacy in preventing HCMV 32 acquisition in phase II trials. However, the mechanism of vaccine protection remains unknown. 33Plasma from 33 gB/MF59 vaccinees at peak immunogenicity was tested for gB epitope

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“…This question is, of course, of paramount importance with respect to the issue of vaccination, since a maternal vaccine that reduces the magnitude of CMV disease in an infant would be judged a success, even if occasional transmission occurred. Some experts have expressed the view that there is no evidence that maternal immunity to CMV provides protection against either congenital infection or the long-term sequelae associated with congenital transmission (27). However, it is clear that the risks of transmission in the context of primary infection are strikingly different from those seen in the context of recurrent infection.…”

Section: Correlates Of Protective Maternal Immunity and Potential Formentioning

confidence: 99%

Progress toward Development of a Vaccine against Congenital Cytomegalovirus Infection

Schleiss

Permar

Plotkin

2017

Clin Vaccine Immunol

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A vaccine against congenital human cytomegalovirus (CMV) infection is a major public health priority. Congenital CMV causes substantial long-term morbidity, particularly sensorineural hearing loss (SNHL), in newborns, and the public health impact of this infection on maternal and child health is underrecognized. Although progress toward development of a vaccine has been limited by an incomplete understanding of the correlates of protective immunity for the fetus, knowledge about some of the key components of the maternal immune response necessary for preventing transplacental transmission is accumulating. Moreover, although there have been concerns raised about observations indicating that maternal seropositivity does not fully prevent recurrent maternal CMV infections during pregnancy, it is becoming increasing clear that preconception immunity does confer some measure of protection against both CMV transmission and CMV disease (if transmission occurs) in the newborn infant. Although the immunity to CMV conferred by both infection and vaccination is imperfect, there are encouraging data emerging from clinical trials demonstrating the immunogenicity and potential efficacy of candidate CMV vaccines. In the face of the knowledge that between 20,000 and 30,000 infants are born with congenital CMV in the United States every year, there is an urgent and compelling need to accelerate the pace of vaccine trials. In this minireview, we summarize the status of CMV vaccines in clinical trials and provide a perspective on what would be required for a CMV immunization program to become incorporated into clinical practice.

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Congenital Human Cytomegalovirus Infection and the Enigma of Maternal Immunity

Cited by 153 publications

References 44 publications

Brain‐resident memory CD8⁺ T cells induced by congenital CMV infection prevent brain pathology and virus reactivation

Brain‐resident memory CD8⁺ T cells induced by congenital CMV infection prevent brain pathology and virus reactivation

HCMV glycoprotein B subunit vaccine efficacy was mediated by non-neutralizing antibody effector functions

Progress toward Development of a Vaccine against Congenital Cytomegalovirus Infection

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Congenital Human Cytomegalovirus Infection and the Enigma of Maternal Immunity

Cited by 153 publications

References 44 publications

Brain‐resident memory CD8+ T cells induced by congenital CMV infection prevent brain pathology and virus reactivation

Brain‐resident memory CD8+ T cells induced by congenital CMV infection prevent brain pathology and virus reactivation

HCMV glycoprotein B subunit vaccine efficacy was mediated by non-neutralizing antibody effector functions

Progress toward Development of a Vaccine against Congenital Cytomegalovirus Infection

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Brain‐resident memory CD8⁺ T cells induced by congenital CMV infection prevent brain pathology and virus reactivation

Brain‐resident memory CD8⁺ T cells induced by congenital CMV infection prevent brain pathology and virus reactivation