Unfortunately, except for this paper, GPCMV gB vaccine studies have not been tested for neutralizing antibody capability on non-fibroblast cells, which limits comparisons to other studies

Unfortunately, except for this paper, GPCMV gB vaccine studies have not been tested for neutralizing antibody capability on non-fibroblast cells, which limits comparisons to other studies. the viral pentamer complex (PC) for endocytic pathway cell access unlike fibroblasts cells that express the viral receptor platelet derived growth factor receptor alpha (PDGFRA) to enable entry by direct cell fusion independent of the PC. Anti-gBwt sera was approximately 2-fold (renal epithelial) to 3-fold (fibroblasts) more effective at neutralizing computer virus compared to anti-gBTMD sera. Both gB vaccines were weakest against computer virus neutralization on trophoblasts. Knockout of PDGFRA cell receptor on fibroblast cells (GPKO) rendered computer virus dependent upon the PC pathway for cell access and anti-gB GPCMV NA50 was more much like epithelial cells. In a gBwt vaccine protection study, vaccination of animals significantly reduced, but did not prevent dissemination of wild type GPCMV challenge computer virus to target organs. Depletion of match in vivo experienced limited impact on vaccine efficacy. Overall, a full length gB antigen has the potential to EPZ004777 hydrochloride improve neutralizing antibody titer but fails to fully prevent computer virus dissemination and likely Mouse monoclonal to ELK1 congenital contamination. Keywords: guinea pig, cytomegalovirus, vaccines, glycoprotein gB, neutralization, congenital contamination Introduction Human cytomegalovirus (HCMV) is usually a ubiquitous pathogen and a leading cause of congenital disease, occurring in approximately 1% of newborns in the US [1]. In congenital HCMV contamination, the greatest risk is usually to mothers who acquire a main infection during pregnancy and consequently a vaccine against congenital CMV (cCMV) is usually a high priority. Any intervention strategy, or therapy, for HCMV should ideally be evaluated in a pre-clinical animal model. HCMV is usually species-specific, making direct study of contamination in animal models EPZ004777 hydrochloride untenable. Species specific animal CMV crosses the placenta in both rhesus macaque (rhesus cytomegalovirus computer virus, RhCMV) and guinea pig (guinea pig cytomegalovirus, GPCMV) [2, 3]. The guinea pig is the only small animal model for cCMV and the focus of this paper. Both human and guinea pig placentas are hemomonochorial, made up of a homogenous layer of trophoblast cells separating maternal and fetal blood circulation [4, 5]. The guinea pig gestation period (approximately 65 days) is divided into three trimesters much like human pregnancy. Furthermore, congenitally infected newborn pups have comparable disease symptoms as humans, eg. sensorineural hearing loss (SNHL) [6]. Consequently, the guinea pig is usually potentially well suited for the screening of intervention and vaccine strategies against cCMV. The GPCMV genome has been sequenced and the computer virus encodes conserved genes with HCMV [7, 8]. Importantly, GPCMV encodes functional viral glycoprotein complexes to HCMV (gB, gH/gL/gO, gM/gN and gH-based pentamer), which are important for computer virus cell access [9C11]. The GPCMV viral gH based pentamer, or pentamer complex (PC), was demonstrated to be necessary for computer virus contamination of non-fibroblast cells, via an endocytic access pathway much like clinical strains of HCMV, computer virus dissemination in animals and congenital contamination [10C12]. In HCMV, the viral glycoprotein complexes are important neutralizing antibody EPZ004777 hydrochloride targets and GPCMV glycoprotein complexes are similarly immunogenic [9, 13C15]. Although numerous vaccine strategies and target antigens have been evaluated against HCMV, the gB glycoprotein remains a significant focus in various vaccine methods, either as a standalone antigen, or in conjunction with other target antigens [16]. A renewed desire for gB-based HCMV vaccine is also due to novel insight of action of non-neutralizing antibodies against gB that potentially enhances vaccine protection against HCMV [17]. In clinical trials, a subunit gB vaccine attains at best about 50% efficacy against maternal contamination [18]. GPCMV gB is usually a neutralizing target antigen [14, 19] and essential for computer virus growth on all cell types [9, 10]. In the guinea pig model, the gB antigen has been the most extensively analyzed vaccine antigen against cCMV. Either as a subunit EPZ004777 hydrochloride vaccine approach [19], or expressed in recombinant vaccine vector delivery.