Congenital Cytomegalovirus: a “Now” Problem—No Really, Now

Bernstein, David I.

doi:10.1128/cvi.00491-16

Cited by 6 publications

(4 citation statements)

References 27 publications

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“…To date, there is no vaccine available that prevents primary or reactivation of CMV infection even though a vaccine would be the best chance to reduce the burden of CMV infection. However, several vaccine candidates are in clinical development, and a vaccine against CMV was classified as a top priority by “The National Vaccine Advisory Committee” in the US in 2004 which has triggered commercial interest [ 15 – 19 ]. In order to develop public health recommendations regarding the use of a CMV vaccine once available in the future, representative epidemiological data on the susceptibility of the population and the burden of CMV infection are essential.…”

Section: Discussionmentioning

confidence: 99%

“…However, several vaccine candidates are currently being tested in clinical trials [ 15 – 17 ]. A vaccine against CMV was classified as a top priority by "The National Vaccine Advisory Committee" in the US in 2004, based on the estimation that the disease burden of congenital CMV infection is as high as the disease burden due to congenital rubella before the introduction of rubella vaccinations [ 18 , 19 ]. Representative epidemiological data on the CMV susceptibility of the population are essential for decision making in the fields of public health and primary prevention through immunization.…”

Section: Introductionmentioning

confidence: 99%

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Cytomegalovirus (CMV) seroprevalence in the adult population of Germany

et al. 2018

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BackgroundInfection with cytomegalovirus (CMV) remains asymptomatic in most immunocompetent hosts, but is the leading cause of congenital viral infection worldwide and can be life-threatening in immunocompromised individuals. We aimed to assess CMV seroprevalence in a nationally representative sample of adults in Germany and to identify sociodemographic factors associated with CMV seropositivity.MethodsBlood samples from 6552 participants (18–79 years) of the “German National Health Interview and Examination Survey 1998”, a population-based sample of the adult population in Germany, were tested for the presence of CMV antibodies using an Ig-multiplex assay. Weighted seroprevalence was calculated and weighted binomial regression was used to identify factors associated with CMV seropositivity.ResultsOverall CMV seroprevalence was 56.7% (95%CI: 54.8–58.7%), with a higher seroprevalence in women (62.3%) than in men (51.0%). Seroprevalence increased with age: from 31.8% to 63.7% in men and from 44.1% to 77.6% in women when comparing the 18–29 with the 70–79 year age-group, respectively. CMV seroprevalence in women of childbearing age (18–45 years) was 51.7%. Factors significantly associated with CMV seropositivity were age, country of birth, smoking status, education, living in northern Germany and number of household members. In addition, having attended child care was associated with seropositivity in men, and number of siblings and living in East Germany in women.ConclusionOur results indicate that half the women of childbearing age were susceptible for primary CMV infection during pregnancy. CMV screening during pregnancy and informing seronegative women about CMV risk reduction measures could prevent congenital CMV infections with its serious consequences.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cytomegalovirus (CMV) seroprevalence in the adult population of Germany

et al. 2018

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“…An estimated 25% of cases of hearing loss in young children in the USA has been attributed to cCMV [14]. The high prevalence of maternal CMV infection and incidence of cCMV worldwide [3,[15][16][17][18] has motivated the development of vaccines [19,20]. No vaccine is as yet registered, but several candidate vaccines are well past the stage of early development and are being evaluated in clinical trials [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Short- and long-term impact of vaccination against cytomegalovirus: a modeling study

Rozhnova

Kretzschmar

Klis

et al. 2020

BMC Med

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Background: Infection with cytomegalovirus (CMV) is highly prevalent worldwide and can cause severe disease in immunocompromised persons and congenitally infected infants. The disease burden caused by congenital CMV infection is high, especially in resource-limited countries. Vaccines are currently under development for various target groups. Methods: We evaluated the impact of vaccination strategies and hygiene intervention using transmission models. Model parameters were estimated from a cross-sectional serological population study (n = 5179) and a retrospective birth cohort (n = 31, 484), providing information on the age-and sex-specific CMV prevalence and on the birth prevalence of congenital CMV (cCMV). Results: The analyses show that vertical transmission and infectious reactivation are the main drivers of transmission. Vaccination strategies aimed at reducing transmission from mother to child (vaccinating pregnant women or women of reproductive age) can yield substantial reductions of cCMV in 20 years (31.7-71.4% if 70% of women are effectively vaccinated). Alternatively, hygiene intervention aimed at preventing CMV infection and re-infection of women of reproductive age from young children is expected to reduce cCMV by less than 2%. The effects of large-scale vaccination on CMV prevalence can be substantial, owing to the moderate transmissibility of CMV at the population level. However, as CMV causes lifelong infection, the timescale on which reductions in CMV prevalence are expected is in the order of several decades. Elimination of CMV infection in the long run is only feasible for a vaccine with a long duration of protection and high vaccination coverage. Conclusions: Vaccination is an effective intervention to reduce the birth prevalence of cCMV. Population-level reductions in CMV prevalence can only be achieved on a long timescale. Our results stress the value of vaccinating pregnant women and women of childbearing age and provide support for the development of CMV vaccines and early planning of vaccination scenarios and rollouts.

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“…Furthermore, infusion with hyperimmune globulins to control viremia is not efficient [7]. Given the severity and importance of this virus, "The National Vaccine Advisory Committee" in the US classified the generation of a vaccine against HCMV as a top priority since 2004 [8][9][10]. The major target populations for vaccination are seronegative women of childbearing age and, among the others, seronegative patients awaiting organ transplantation, who are at risk for life-threatening HCMV disease.…”

Section: Introductionmentioning

confidence: 99%

Rationally designed Human Cytomegalovirus gB nanoparticle vaccine with improved immunogenicity

et al. 2020

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Human cytomegalovirus (HCMV) is the primary viral cause of congenital birth defects and causes significant morbidity and mortality in immune-suppressed transplant recipients. Despite considerable efforts in vaccine development, HCMV infection still represents an unmet clinical need. In recent phase II trials, a MF59-adjuvanted gB vaccine showed only modest efficacy in preventing infection. These findings might be attributed to low level of antibodies (Abs) with a neutralizing activity induced by this vaccine. Here, we analyzed the immunogenicity of each gB antigenic domain (AD) and demonstrated that domain I of gB (AD5) is the main target of HCMV neutralizing antibodies. Furthermore, we designed, characterized and evaluated immunogenic responses to two different nanoparticles displaying a trimeric AD5 antigen. We showed that mice immunization with nanoparticles induces sera neutralization titers up to 100-fold higher compared to those obtained with the gB extracellular domain (gBECD). Collectively, these results illustrate with a medically relevant example the advantages of using a general approach combining antigen discovery, protein engineering and scaffold presentation for modern development of subunit vaccines against complex pathogens.

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Congenital Cytomegalovirus: a “Now” Problem—No Really, Now

Cited by 6 publications

References 27 publications

Cytomegalovirus (CMV) seroprevalence in the adult population of Germany

Cytomegalovirus (CMV) seroprevalence in the adult population of Germany

Short- and long-term impact of vaccination against cytomegalovirus: a modeling study

Rationally designed Human Cytomegalovirus gB nanoparticle vaccine with improved immunogenicity

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