Indirect effects of cytomegalovirus infection: Implications for vaccine development

Abstract

Development of a cytomegalovirus (CMV) vaccine is a high priority due to its significant global impact-contributing to mortality in immunosuppressed individuals, neurodevelopmental delay in infected neonates and non-genetic sensorineural hearing loss. The impact of CMV on the general population has been less well studied; however, a wide range of evidence indicates that CMV may increase the risk of atherosclerosis, cancer, immunosenescence, and progression of tuberculosis (TB) and human immunodeficiency virus. Due to the high seroprevalence of CMV worldwide, any modulation of risk by CMV is likely to have a significant impact on the epidemiology of these diseases. This review will evaluate how CMV may cause morbidity and mortality outside of the neonatal and immunosuppressed populations and consider the potential impact of a CMV vaccine on these outcomes. | INTRODUCTIONCytomegalovirus (CMV) is the most common non-genetic cause of sensorineural hearing loss in neonates and a leading cause of neurodevelopmental delay. 1 In the immunocompromised host, CMV reactivation results in vasculopathy, graft rejection and severe end organ damage. 2,3 Subsequently, the development of a vaccine against CMV has been cited as a high priority for the last 2 decades including by the National Institute of Health. 4 CMV has been associated with several distinct disease processes-atherosclerosis, 5-8 cancer 9 and impaired immune response to vaccination. [10][11][12] Additionally, CMV is suspected to enhance the pathogenicity of human immunodeficiency virus (HIV) and tuberculosis (TB). [13][14][15][16] Animal studies and large population based epidemiological studies suggest that CMV may cause disease through mechanisms such as CD8+ memory T-cell inflation 17 ; immunosenescence and immunomodulation. [18][19][20] In addition, reactivation of CMV in local tissues may result in lytic replication and cause direct

CMV and HIV Coinfection in Women from a Region in Eastern Europe

“…A high value of CMV IgG and low level of CD4 cells may have future consequences on PLWH's evolution and developing complications. CMV IgG seropositivity has been associated with immunosenescence and the development of cardiovascular diseases, cancer and other pathologies [28,29]. Patients with higher levels of CD4 and lower levels of CMV IgG are less predisposed to complications.…”

Comprehensive Review of Urinary Tract Infections in Renal Transplant Recipients: Clinical Insights and Management Strategies

“…These vaccinations may indirectly reduce the risk of UTIs by preventing systemic viral infections that can affect the urinary tract. Preventing these viral infections can help maintain the overall health and immunity of the transplant recipient, lowering the susceptibility to UTIs [ 66 ].…”

Antiviral Approach to Cytomegalovirus Infection: An Overview of Conventional and Novel Strategies

“…Candidate vaccines in clinical evaluation include live attenuated, protein subunit, DNA, and viral-vectored approaches. Subunit approaches have focused on the HCMV proteins pp65 and IE-1 as important inducers of cytotoxic T cells and glycoprotein B (gB) as an important inducer of neutralizing antibodies [144,145]. DNA plasmids coding for pp65 and gB have shown preliminary evidence of efficacy in transplant recipients, with the ability to stimulate high levels of neutralizing antibodies [54].…”