Publications

enhancing safety of cytomegalovirus-based vaccine vectors by engaging host intrinsic immunity.	rhesus cytomegalovirus (rhcmv)-based vaccines maintain effector memory t cell responses (tem) that protect ~50% of rhesus monkeys (rms) challenged with simian immunodeficiency virus (siv). because human cmv (hcmv) causes disease in immunodeficient subjects, clinical translation will depend upon attenuation strategies that reduce pathogenic potential without sacrificing cmv's unique immunological properties. we demonstrate that "intrinsic" immunity can be used to attenuate strain 68-1 rhcmv vecto ...	2019	31316006
a live-attenuated rhcmv/siv vaccine shows long-term efficacy against heterologous siv challenge.	previous studies have established that strain 68-1-derived rhesus cytomegalovirus (rhcmv) vectors expressing simian immunodeficiency virus (siv) proteins (rhcmv/siv) are able to elicit and maintain cellular immune responses that provide protection against mucosal challenge of highly pathogenic siv in rhesus monkeys (rms). however, these efficacious rhcmv/siv vectors were replication and spread competent and therefore have the potential to cause disease in immunocompromised subjects. to develop a ...	2019	31316007
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 ...	2020	32134481
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 ...	2020	32713108
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 ...	2020	32820216
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 ...	2020	32922404
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 ...	2020	33232376
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 ...	2021	33766849
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 ...	2021	34228762