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Towards an Effective Vaccine for Cytomegalovirus


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Posted 20 November 2020 - 11:15 AM


Cytomegalovirus is a persistent herpesvirus that is problematic in a few populations, largely harmless in the short term for everyone else, largely unnoticed by those infected, and widely prevalent in the population. Near everyone is infected by the time old age arrives. Unfortunately, CMV appears to be a major factor in the age-related decline of the adaptive immune system, possibly by causing ever more immune cells to become uselessly specialized to target it, leaving too few immune cells for other tasks. This sort of runaway resource misallocation in the immune system is a large problem in the elderly, given that the thymus, where new T cells of the adaptive immune system mature, is near entirely atrophied by late life, reducing the supply of new cells to a trickle. Effective vaccination will help this situation, but there is good reason to think that, for the oldest to benefit, it must be accompanied by selective destruction of cytomegalovirus-focused immune cells, and restoration of the supply of new immune cells.

A research team says it has identified a key marker that will help speed effective vaccine designs for cytomegalovirus (CMV), the most common congenital infection worldwide. The researchers describe an immune surrogate that demonstrates when a vaccine has elicited the necessary antibodies that protect against CMV infection. The finding is already being applied to screen potential vaccines.

"Despite the high global burden of disease, vaccine development to prevent infection remains hampered by challenges in generating protective immunity. The most efficacious CMV vaccine candidate tested to date is a soluble glycoprotein B (gB) subunit vaccine with MF59 adjuvant (gB/MF59), which achieved 50% protection in multiple phase 2 clinical trials. The vaccine-elicited immune responses that conferred this protection have remained unclear. We investigated the humoral immune correlates of protection from CMV acquisition in populations of CMV-seronegative adolescent and postpartum women who received the gB/MF59 vaccine. We found that gB/MF59 immunization elicited distinct CMV-specific immunoglobulin G (IgG)-binding profiles and IgG-mediated functional responses in adolescent and postpartum vaccinees, with heterologous CMV strain neutralization observed primarily in adolescent vaccinees."

"We determined that protection against primary CMV infection in both cohorts was associated with serum IgG binding to gB present on a cell surface but not binding to the soluble vaccine antigen, suggesting that IgG binding to cell-associated gB is an immune correlate of vaccine efficacy. Supporting this, we identified gB-specific monoclonal antibodies that differentially recognized soluble or cell-associated gB, revealing that there are structural differences in cell-associated and soluble gB are relevant to the generation of protective immunity."

"Our results highlight the importance of the native, cell-associated gB conformation in future CMV vaccine design. CMV has been recognized as a top priority for vaccine development for more than 20 years, yet we remain without an approved vaccine. This work provides a way to assure that current and future vaccine candidates stimulate an effective immune response."

Link: https://www.genengne...ne-development/


View the full article at FightAging




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