These are live viruses with selective gene deletions in their membrane proteins that allowed them to assemble after their first infection cycle, but which were unable to infect successive cells ( 12). The 1990s saw the development of the first attenuated vaccines – a new generation of so-called transgenic disabled infectious single cycle (DISC) strains (see Figure 2) ( 11). They have the potential to be one of the most effective ways of vaccinating against CMV, as they can mimic a natural infection ( 10). However, the acknowledgement of the clinical significance of CMV in recent years has stimulated a surge in funding and research interest.Īttenuated vaccines are created by reducing the virulence of a pathogen, while still keeping them viable. Major impediments to the development of a suitable vaccine have likely been down to poor general awareness of the virus and its immunological complexity. No licensed vaccines are currently available, but researchers haven’t been sitting idle the development of CMV vaccines has been ongoing for nearly 50 years ( 9). Similarly, a vaccine for transplant recipients would avoid the need for expensive antiviral treatments that are limited in efficacy and duration, drastically improving patient survival and procedure success rates. Much like the rubella vaccine, a novel vaccine for CMV could protect mothers and their developing infants from CMV. And while antiviral therapies have been invaluable, they are limited by toxicity and the continual emergence of viral resistance. The incidence of CMV infection among transplant recipients is remarkably common, with 20–70 percent of recipients acquiring an infection in the first year post-transplant ( 1), making it one of the most common complications affecting the survival of transplant recipients worldwide ( 8).ĭespite its significant burden, no effective countermeasures are currently in place to protect those at risk, with only basic screening or behavioral measures, such as hand hygiene, available ( 7). Transplant-acquired infections can cause conditions, such as hepatitis, pneumonia and viremia ( 1) – all of which increase the likelihood of transplant rejection and graft-versus-host disease. These infections can occur due to the presence of CMV in the transplanted organ, viral reactivation in the recipient’s tissue, or primary infection in seronegative recipients. Recipients of donated organs and stem cell transplants. CMV is also a threat to the recipients of solid organ or hematopoietic stem cell transplants during immunosuppressive therapy. The magnitude of cCMV is significant, affecting approximately double the number of children living with better-known childhood disorders, such as Down syndrome ( 5), and takes the top spot for infectious hearing loss in children worldwide ( 7). Here, it can wreak havoc on an infant’s developing nervous system ( 5), causing irreversible defects that range from hearing loss, to impaired organ growth and learning disabilities ( 6). The pregnant mother and fetus.If a new or reactivated CMV infection occurs during pregnancy, the virus can be transmitted to the placenta and establish a congenital infection in the developing fetus (cCMV). Though the majority of CMV infections are often benign and of little concern, the virus poses a significant risk to those who struggle to mount an effective immune response – a problem that occurs predominantly in two groups: Given the body’s natural ability to respond quickly to infection, the majority of those infected with CMV are asymptomatic, though some may present with mild symptoms, including fever, sore throat and fatigue. Fortunately, the immune system typically responds quickly, and drives the virus into a latent state, where it remains dormant throughout a person’s life and waits for more favorable conditions ( 4). Once inside the body, it invades a remarkably broad range of cell types to mold cellular functions that support its replication. Though we don’t yet have a full picture of how CMV is transmitted, the virus appears to spread via a range of human bodily fluids, including urine, saliva, blood and tears. It exists as a variety of interrelated strains, both within the environment and those it infects ( 3). ![]() And yet general awareness of CMV and its impact on human health (particularly the risk of congenital infection) is relatively poor.ĬMV has one of the largest viral genomes known to man and is composed of hundreds of proteins (see Figure 1). The virus, which belongs to the Herpesviridae family, infects the majority of people over the course of their lifetime, making it one of the most ubiquitous human pathogens in the world ( 1, 2). To say that cytomegalovirus (CMV) is common would be an understatement.
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