Author(s): Jie Zhong 1 , Rajiv Khanna [[dagger]] 2
congenital infection; human cytomegalovirus; immunization; vaccine
Importance of human cytomegalovirus vaccine
Human cytomegalovirus (HCMV; species human herpesvirus 5) is the most complex of the eight human herpesvirus species and has a 235-kbp double-stranded DNA that encodes 165 genes  . Although HCMV infects approximately 40-60% of the developed world's population, it does not cause clinical disease in immunocompetent individuals, except mononucleosis-like illness in small numbers of infected people. However, HCMV-associated clinical disease has been recognized in three populations:
* Neonates with immature immune systems
* Transplant recipients with impaired immune systems due to the use of drugs to suppress rejection
* HIV-infected patients with impaired immune systems due to the decline of CD4+ T cells
Congenital HCMV infection is the most common intrauterine infection and 0.3-2.4% of neonates (depending on the seroprevalence of the population examined) are born with HCMV infection worldwide  . Of the neonates with congenital HCMV infection, 10% have symptoms of irreversible CNS involvement in the form of microcephaly, encephalitis, seizures, deafness (56% of symptomatic infants with HCMV infection), upper-motor neuron disorders and psychomotor retardation  . The 90% of congenitally infected children who appear to be healthy at birth will develop serious sequelae, including mental retardation and hearing loss (15% of asymptomatic infants with HCMV infection) over the course of several years. More importantly, long-term follow-up studies indicate that up to 10-20% of the remaining 80% of affected infants have serious life-threatening organ dysfunction and death  . It has been shown that each year in the USA alone, 8000 newborns carry congenital HCMV infection and each one of these children costs the US healthcare system more than US$300,000  .
In addition to neonates, HCMV infection has a significant impact on immunocompromised individuals, such as transplant recipients and HIV-infected patients. HCMV is the most important viral pathogen affecting transplant recipients, including both solid organ transplant and allogeneic hematopoietic stem cell transplant (HSCT) recipients whose immune systems are suppressed by drugs used to prevent graft rejection. HIV-infected patients with CD4+ T-cell counts less than 100/µl are also impacted by HCMV infection due to the loss of HCMV-specific CD4+ T-cell response, which is required for the maintenance of virus-specific CD8 + T cells  . However, in recent years, the incidence of HCMV disease has declined significantly in HIV-infected patients owing to the application of therapeutic drugs to limit HIV replication, which restore CD4+ T-cell function and anti-HCMV cellular immunity [7-9] . Although the need for a HCMV vaccine for HIV patients is not as urgent as previously estimated, the benefit of HCMV vaccine for congenital infection in neonates and in transplant recipients is huge and obvious. Based on the cost and human suffering that would be relieved by reducing the disease burden associated with HCMV infection, in 1999 the Institute of Medicine (USA) assigned the development of HCMV vaccine as a level 1 priority  .
Immune response to HCMV infection
Although the primary immune response induced by initial infection with HCMV does not clear the...