Perinatal Outcomes of Non-Primary Maternal Cytomegalovirus Infection: A 15-Year Experience

Simonazzi, Giuliana; Curti, Alessandra; Cervi, Francesca; Gabrielli, Liliana; Contoli, M.; Capretti, Maria Grazia; Rizzo, Nicola; Guerra, Brunella; Farina, Antonio; Lazzarotto, Tiziana

doi:10.1159/000477168

Cited by 44 publications

(40 citation statements)

References 26 publications

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“…Prospective studies showed that maternal immunity is protective against congenital HCMV infection, with highly significantly reduced rates of vertical transmission in women with nonprimary compared to primary infections. 125,126 Primary infections result in HCMV transmission in approximately 30% of affected pregnancies, whereas preexisting maternal immunity confers a 69% reduction of the risk of congenital HCMV in future pregnancies. 127,128 Moreover, there is evidence that sequelae of congenital HCMV infection are reduced in the setting of preconception maternal immunity.…”

Section: Rna Hcmv Vaccinesmentioning

confidence: 99%

Development of novel vaccines against human cytomegalovirus

Cui

Snapper

2019

Human Vaccines & Immunotherapeutics

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Congenital human cytomegalovirus (HCMV) infection and HCMV infection of the immunosuppressed patients cause significant morbidity and mortality, and vaccine development against HCMV is a major public health priority. Efforts to develop HCMV vaccines have been ongoing for 50 y, though no HCMV vaccine has been licensed; encouraging and promising results have obtained from both preclinical and clinical trials. HCMV infection induces a wide range of humoral and T cell-mediated immune responses, and both branches of immunity are correlated with protection. In recent years, there have been novel approaches toward the development of HCMV vaccines and demonstrated that vaccine candidates could potentially provide superior protection over natural immunity acquired following HCMV infection. Further, rationally designed HCMV protein antigens that express native conformational epitopes could elicit optimal immune response. HCMV vaccine candidates, using a multi-antigen approach, to maximize the elicited protective immunity will most likely be successful in development of HCMV vaccine.

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Section: Rna Hcmv Vaccinesmentioning

confidence: 99%

Development of novel vaccines against human cytomegalovirus

Cui

Snapper

2019

Human Vaccines & Immunotherapeutics

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“…Thus, although prior maternal infection with CMV does not provide complete protection against transmission to the fetus, it does clearly reduce the risk. Indeed, two recent prospective studies both indicated a protective effect of maternal immunity against congenital CMV infection, with highly significantly reduced rates of vertical transmission in women with nonprimary compared to primary infections (31,32). Thus, although imperfect, there is evidence to support the contention that preconception maternal immunity to CMV is a barrier to vertical transmission.…”

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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“…Recent studies show that seropositive mothers have high rates of reinfection with new virologic strains of CMV, ranging from 18-30% [13,14], suggesting that reinfection could be a major mode of non-primary cCMV infection. Birth prevalence of non-primary cCMV infection among infants born to all seropositive women is estimated to be 1%, yet placental transmission has been reported to be as high as 3.4% in women who have evidence of reinfection during pregnancy [8,15]. Seronegative mothers residing in areas of low CMV seroprevalence have low rates of maternal CMV acquisition ranging from 1-3% [1], yet placental CMV transmission rates in these cases of primary maternal CMV infection during pregnancy range from 30-50% [16][17][18].…”

mentioning

confidence: 99%

Impact of Maternal Immunity on Congenital Cytomegalovirus Birth Prevalence and Infant Outcomes: A Systematic Review

Coppola

Mangold²,

Cantrell

et al. 2019

Vaccines

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Congenital cytomegalovirus (cCMV) is the leading non-genetic cause of sensorineural hearing loss (SNHL), and efforts are geared towards prevention through vaccine development. Transmission rates following primary maternal infection occur at rates of 30-40%, however reported placental rates upon non-primary maternal infection is reported to be less than <4%. There is significant debate about whether this reduction in transmission rate is due to pre-existing maternal immunity, which could identify possible immunologic targets for vaccines. To address this question, we performed a systemic review of the literature using Preferred Reporting Items for Systematic Review and Analysis (PRISMA) guidelines. We identified cohort studies in high CMV seroprevalent (>80%) areas or in developing regions that examined a cohort of at least 50 infants for congenital CMV acquisition. We identified 19 articles that met criteria and were further categorized based on pre-conception serology, maternal seroprevalence, or previously known seroprevalence. Birth prevalence rates ranged from 0.4% to 6% (median 1.1%), with the studies reporting on clinical outcome (16/19 studies) noting the majority of infected infants as asymptomatic. We also utilized a recent study that differentiated primary maternal infections from chronic infections in a highly seropositive population to calculate a placental transmission rate in women with pre-existing immunity compared to that of no pre-existing immunity. This work confirms a low cCMV birth prevalence in highly seropositive populations, indicates via a calculated placental transmission rate that the CMV placental transmission rate is lower in non-primary infection than that of primary infection, and reveals gaps in data for further research aiming to identify targets for vaccine development.Vaccines 2019, 7, 129 2 of 13 leading non-genetic cause of SNHL [9,11]. Furthermore, as many as 5% of infants without recognizable CMV-associated sequelae at birth may develop microcephaly or neurodevelopmental deficits within the first year of life [10].Placental transmission of CMV occurs in mothers with both prior natural immunity to CMV, termed 'non-primary CMV infection', and among seronegative mothers who contract CMV during pregnancy, termed 'primary infection' [2,5,12]. Congenital CMV infections occur in chronic CMV-infected women as a result from either reactivation of the virus from a previous infection or reinfection. The contribution of each of these potential routes of infection to non-primary cCMV incidence is not known. Recent studies show that seropositive mothers have high rates of reinfection with new virologic strains of CMV, ranging from 18-30% [13,14], suggesting that reinfection could be a major mode of non-primary cCMV infection. Birth prevalence of non-primary cCMV infection among infants born to all seropositive women is estimated to be 1%, yet placental transmission has been reported to be as high as 3.4% in women who have evidence of reinfection during pregnancy [8,15]. Seronegative mothe...

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Perinatal Outcomes of Non-Primary Maternal Cytomegalovirus Infection: A 15-Year Experience

Cited by 44 publications

References 26 publications

Development of novel vaccines against human cytomegalovirus

Development of novel vaccines against human cytomegalovirus

Progress toward Development of a Vaccine against Congenital Cytomegalovirus Infection

Impact of Maternal Immunity on Congenital Cytomegalovirus Birth Prevalence and Infant Outcomes: A Systematic Review

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