Abstract
Human cytomegalovirus (HCMV) core fusion machinery proteins gB and gH/gL, and accessory proteins UL128/UL130/UL131A, are the key envelope proteins that mediate HCMV entry into and infection of host cells. To determine whether these HCMV envelope proteins could elicit neutralizing activities synergistically, we immunized rabbits with individual or various combinations of these proteins adsorbed to aluminum hydroxide mixed with CpG-ODN. We then analyzed serum neutralizing activities with multiple HCMV laboratory strains and clinical isolates. HCMV trimeric gB and gH/gL elicited high and moderate titers of HCMV neutralizing activity, respectively. HCMV gB in combination with gH/gL elicited up to 17-fold higher HCMV neutralizing activities compared to the sum of neutralizing activity elicited by the individual proteins analyzed with both fibroblasts and epithelial cells. HCMV gB+gH/gL+UL128/UL130/UL131A in combination increased the neutralizing activity up to 32-fold compared to the sum of neutralizing activities elicited by the individual proteins analyzed with epithelial cells. Adding UL128/UL130/UL131A to gB and gH/gL combination did not increase further the HCMV neutralizing activity analyzed with fibroblasts. These data suggest that the combination of HCMV core fusion machinery envelope proteins gB+gH/gL or the combination of gB and pentameric complex could be ideal vaccine candidates that would induce optimal immune responses against HCMV infection.
Highlights
Human cytomegalovirus (HCMV) belongs to the human herpesvirus (HHV) family, and HCMV is known as HHV5
Recombinant UL128/UL130/UL131A proteins were expressed where the coding sequences for UL128, UL130 and UL131A in tandem were separated by a (Gly4 Ser)3 linker coding sequence in between
Synthesized DNA coding for recombinant HCMV gH/gL or UL128/UL130/UL131A protein was cloned into pOptiVEC vector and transfected Chinese hamster ovary (CHO) cells
Summary
Human cytomegalovirus (HCMV) belongs to the human herpesvirus (HHV) family, and HCMV is known as HHV5. HCMV infection in transplantation recipients causes hepatitis and pneumonitis, HCMV viremia can significantly increase the chance of graft rejection and graft failure in solid organ transplant patients, as well as graft-versus-host disease in hematopoietic stem cell transplant patients [9,10,11,12]. Despite the fact that there have been many preventive procedures and treatments developed for controlling HCMV viremia in solid organ and hematopoietic stem cell transplant recipients such as active monitoring and management with novel and highly efficient antiviral drugs, HCMV infection is still one of the most common complications that negatively affects patient survival [13,14,15,16,17]
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