Cytomegalovirus (CMV) is a common virus affecting people worldwide. It belongs to the herpesvirus family, meaning that once a person is infected, the virus remains in their body for life, often in a dormant state. A vaccine for CMV is important due to its potential to cause severe health complications, especially in vulnerable populations. Efforts are underway to create an effective vaccine and reduce the public health burden of this virus.
Understanding Cytomegalovirus (CMV)
CMV is a member of the Herpesviridae family, also known as Human Herpesvirus 5 (HHV-5). This DNA virus is transmitted through direct contact with various body fluids from an infected person, including saliva, urine, blood, breast milk, tears, semen, and vaginal fluids. While casual contact typically does not spread CMV, prolonged or intimate exposure is a common mode of transmission.
Once infected, the virus remains latent within the body’s cells and may reactivate later, especially if the immune system becomes weakened. In healthy individuals, CMV often causes no noticeable symptoms or only mild, flu-like symptoms such as fever, swollen glands, or fatigue. Its high global prevalence is notable; estimates suggest that the worldwide seroprevalence in the general population is around 83%, with rates reaching as high as 100% in some developing countries. In the United States, over half of adults are infected by age 40, and nearly one in three children are infected by age five.
The Urgent Need for a CMV Vaccine
Congenital CMV infection, which occurs when a pregnant person transmits the virus to their unborn baby, is a primary concern. This infection is recognized as the most common infectious cause of birth defects and long-term disabilities in infants.
Infants born with congenital CMV may experience a range of serious issues, including hearing loss, which can be detected at birth or develop later in childhood. Other potential complications include developmental delays, vision problems, microcephaly (abnormally small head size), seizures, and issues affecting the liver, spleen, and lungs. Approximately 1 to 4 percent of women experience a primary CMV infection during pregnancy, and this initial infection carries a higher risk of passing the virus to the fetus.
Beyond congenital infection, CMV poses significant risks to individuals with compromised immune systems. This includes organ transplant recipients, where CMV can lead to severe, life-threatening illnesses such as pneumonia, retinitis, or gastrointestinal issues. Similarly, individuals with HIV/AIDS or those undergoing chemotherapy are at heightened risk for CMV reactivation, which can result in serious organ damage and increased morbidity and mortality.
Approaches to CMV Vaccine Development
Developing a CMV vaccine is complex due to the virus’s intricate nature. One long-standing approach involves live-attenuated vaccines, which use a weakened form of the virus to stimulate immunity without causing severe disease. This method aims to mimic a natural infection, potentially generating broad and long-lasting immune protection.
Another approach involves subunit vaccines, which focus on specific viral proteins to trigger an immune response. A prominent target for these vaccines is glycoprotein B (gB), a protein involved in the virus’s entry into host cells. Vaccines targeting gB aim to induce neutralizing antibodies that can block infection. Another protein, phosphoprotein 65 (pp65), is also being investigated as a target for subunit vaccines, often in combination with gB, to stimulate a more comprehensive immune response involving both antibodies and T-cells.
Newer technologies, such as messenger RNA (mRNA) vaccines, are also being applied. These platforms deliver genetic instructions to the body’s cells, prompting them to produce viral proteins, like gB, which train the immune system to recognize and fight the virus. Despite these diverse approaches, challenges remain in creating a vaccine that effectively prevents primary infection, congenital transmission, and disease in immunocompromised individuals, given CMV’s ability to establish lifelong latency and evade immune detection.
Current Progress and Future Outlook
Several CMV vaccine candidates are currently undergoing evaluation in clinical trials, representing different stages of development. One of the leading candidates, a recombinant subunit vaccine targeting glycoprotein B (gB), has shown promise in clinical trials, particularly for preventing congenital CMV infection in women. This candidate has progressed through various phases, demonstrating its ability to reduce the incidence of primary infection. Other approaches, including mRNA-based vaccines, are also in earlier phases of clinical development, investigating their safety and ability to induce an immune response.
The primary target populations for these vaccine candidates include women of childbearing age, aiming to prevent congenital CMV transmission to their infants. Adolescents are also considered a target group to prevent primary infection before reproductive age. Additionally, some vaccines are being developed with a focus on immunocompromised individuals, such as organ transplant recipients, to mitigate the severe complications CMV can cause in these patients.
A successful CMV vaccine could significantly reduce the incidence of congenital CMV infection, thereby preventing associated long-term disabilities like hearing loss and developmental delays in thousands of infants annually. For immunocompromised patients, a vaccine could improve outcomes by reducing the burden of CMV-related disease and complications following transplantation or other immunosuppressive conditions. While several years may pass before an effective CMV vaccine is broadly available, the ongoing research and clinical trial progress offer optimism for a future with diminished CMV-related health challenges.