HCMV is the most common viral infection in newborns worldwide and affects more children than other more commonly known conditions such as Down syndrome, fetal alcohol syndrome or spina bifida. In the US, where the most extensive epidemiological studies have been conducted, the incidence of congenital HCMV infection is estimated at 40,000 cases annually.
It is estimated that almost 400 children die each year of congenital HCMV and more than 5,000 children develop permanent disabilities. Although epidemiological studies have been less extensive in Europe, available data suggest a similar incidence of congenital infection and disease. The estimated costs associated with HCMV disease for the US health care system is estimated at 1.86 billion dollars annually.
In 2000, the US National Academy of Medicine indicated that a vaccine preventing congenital HCMV infection would be highly cost-effective and ranked HCMV at the highest priority level for vaccine development. As a result, most large vaccine manufacturers, including GSK Biologicals, Merck, Sanofi and Astellas, have an HCMV program. In parallel, several monoclonal antibody manufacturers, including Novartis and Genentech, are working on anti-HCMV antibodies.
The risk of these programs is significantly increased by our poor understanding of immune control of HCMV following primary infection and by the absence of correlate of protection. Several key clinical trials provided a proof-of-principle that antibodies against HCMV envelope glycoproteins could efficiently control HCMV replication in vivo in humans.
Our project will provide unique information regarding the characteristics of the antibodies that should be induced or administered to prevent congenital HCMV infection. The project will provide the first in depth analysis of the IgG response to HCMV envelope glycoproteins during primary infection. It will also provide the first multi-parametric analysis of serological correlates of HCMV transmission to the fetus. The identification of the mechanisms underlying viral control and tissues damage at the materno-fetal interface will have a considerable impact on the development and on the evaluation of new vaccines and antibody-based therapies against congenital HCMV infection.