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neutralization of rhesus cytomegalovirus il-10 reduces horizontal transmission and alters long-term immunity.human cytomegalovirus (hcmv) causes severe disease in infants and immunocompromised people. there is no approved hcmv vaccine, and vaccine development strategies are complicated by evidence of both persistent infection and reinfection of people with prior immunity. the greatest emphasis has been placed on reducing transmission to seronegative pregnant women to prevent vertical transmission and its potentially severe sequelae. increasing evidence suggests that the earliest host-hcmv interactions ...201931189602
comparison of vaccination with rhesus cmv (rhcmv) soluble gb with a rhcmv replication-defective virus deleted for mhc class i immune evasion genes in a rhcmv challenge model.a human cytomegalovirus (hcmv) vaccine to prevent infection and/or reduce disease associated with congenital infection or visceral disease in transplant recipients is a high priority, but has remained elusive. we created a disabled infectious single cycle rhesus cmv (rhcmv) deleted for glycoprotein l (gl) and the mhc class i immune evasion genes rh178 and rh182-189, and restored its epithelial cell tropism by inserting the rh128-131a genes. the resulting virus, rhcmvrδgl/178/182-189, was used to ...201930522906
rhesus cytomegalovirus-specific cd8+ cytotoxic t lymphocytes do not become functionally exhausted in chronic sivmac239 infection.cd8+ cytotoxic t lymphocytes (ctls) exert potent antiviral activity after hiv/siv infection. however, efforts to harness the antiviral efficacy of ctls for hiv/siv prophylaxis and therapy have been severely hindered by two major problems: viral escape and exhaustion. by contrast, ctls directed against human cytomegalovirus (hcmv), a ubiquitous chronic herpesvirus, seldom select for escape mutations and remain functional and refractory to exhaustion during chronic hcmv and hiv infection. recently ...202032922404
rhcmv serostatus and vaccine adjuvant impact immunogenicity of rhcmv/siv vaccines.rhesus cytomegalovirus (rhcmv) strain 68-1-vectored simian immunodeficiency virus (rhcmv/siv) vaccines are associated with complete clearance of pathogenic siv challenge virus, non-canonical major histocompatibility complex restriction, and absent antibody responses in recipients previously infected with wild-type rhcmv. this report presents the first investigation of rhcmv/siv vaccines in rhcmv-seronegative macaques lacking anti-vector immunity. fifty percent of rhesus macaques (rm) vaccinated ...202032820216
immunophenotyping of rhesus cmv-specific cd8 t-cell populations.a vaccine to ameliorate cytomegalovirus (cmv)-related pathogenicity in transplantation patients is considered a top priority. a therapeutic vaccine must include components that elicit both neutralizing antibodies, and highly effective cd8 t-cell responses. the most important translational model of vaccine development is the captive-bred rhesus macaque (macaca mulatta) of indian origin. there is a dearth of information on rhesus cytomegalovirus (rhcmv)-specific cd8 t cells due to the absence of w ...202032713108
animal models of congenital cytomegalovirus transmission: implications for vaccine development.although cytomegaloviruses (cmvs) are species-specific, the study of nonhuman cmvs in animal models can help to inform and direct research aimed at developing a human cmv (hcmv) vaccine. because the driving force behind the development of hcmv vaccines is to prevent congenital infection, the animal model in question must be one in which vertical transmission of virus occurs to the fetus. fortunately, two such animal models-the rhesus macaque cmv and guinea pig cmv-are characterized by congenital ...202032134481
in vitro and in vivo characterization of a recombinant rhesus cytomegalovirus containing a complete genome.cytomegaloviruses (cmvs) are highly adapted to their host species resulting in strict species specificity. hence, in vivo examination of all aspects of cmv biology employs animal models using host-specific cmvs. infection of rhesus macaques (rm) with rhesus cmv (rhcmv) has been established as a representative model for infection of humans with hcmv due to the close evolutionary relationships of both host and virus. however, the only available rhcmv clone that permits genetic modifications is bas ...202033232376
interleukin-15 response signature predicts rhcmv/siv vaccine efficacy.simian immunodeficiency virus (siv) challenge of rhesus macaques (rms) vaccinated with strain 68-1 rhesus cytomegalovirus (rhcmv) vectors expressing siv proteins (rhcmv/siv) results in a binary outcome: stringent control and subsequent clearance of highly pathogenic siv in ~55% of vaccinated rms with no protection in the remaining 45%. although previous work indicates that unconventionally restricted, siv-specific, effector-memory (em)-biased cd8+ t cell responses are necessary for efficacy, the ...202134228762
cytomegaloviral determinants of cd8+ t cell programming and rhcmv/siv vaccine efficacy.simian immunodeficiency virus (siv) insert-expressing, 68-1 rhesus cytomegalovirus (rhcmv/siv) vectors elicit major histocompatibility complex e (mhc-e)- and mhc-ii-restricted, siv-specific cd8+ t cell responses, but the basis of these unconventional responses and their contribution to demonstrated vaccine efficacy against siv challenge in the rhesus monkeys (rms) have not been characterized. we show that these unconventional responses resulted from a chance genetic rearrangement in 68-1 rhcmv t ...202133766849
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