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seroprevalence of neutralizing antibodies to human adenoviruses type-5 and type-26 and chimpanzee adenovirus type-68 in healthy chinese adults.replication-defective adenoviruses have been utilized as candidate vaccine vectors. however, clinical application of the best-studied human adenovirus type-5 (adhu5) is limited by the high prevalence of preexisting neutralizing antibodies resulting from natural infection. therefore, rare adenovirus serotypes, such as human adenovirus type-26 (adhu26) and chimpanzee adenovirus type-68 (adc68), have been employed as substitutes for adhu5. however, few studies have described the epidemiology of pre ...201323588735
first-in-human evaluation of the safety and immunogenicity of a recombinant adenovirus serotype 26 hiv-1 env vaccine (ipcavd 001).we report the first-in-human safety and immunogenicity assessment of a prototype ad26 vector-based human immunodeficiency virus (hiv) vaccine in humans.201323125444
characterization of humoral and cellular immune responses elicited by a recombinant adenovirus serotype 26 hiv-1 env vaccine in healthy adults (ipcavd 001).adenovirus serotype 26 (ad26) has been developed as a novel candidate vaccine vector for human immunodeficiency virus type 1 (hiv-1) and other pathogens. the primary safety and immunogenicity data from the integrated preclinical/clinical aids vaccine development program (ipcavd) 001 trial, the first-in-human evaluation of a prototype ad26 vector-based vaccine expressing clade a hiv-1 env (ad26.enva.01), are reported concurrently with this article. here, we characterize in greater detail the humo ...201323125443
adenovirus serotype 26 utilizes cd46 as a primary cellular receptor and only transiently activates t lymphocytes following vaccination of rhesus monkeys.the cellular receptor utilized by adenovirus serotype 26 (ad26) has remained unclear. here we show that ad26 transduction is cd46-dependent and is efficiently blocked by anti-cd46 but not anti-car antibodies, demonstrating that ad26 utilizes cd46 as a primary cellular receptor. moreover, following ad26 vaccination of rhesus monkeys, we did not observe sustained activation of peripheral or mucosal vector-specific cd4(+) t lymphocytes. these data contribute to our understanding of ad26 as a candid ...201222811531
acute meningoencephalitis caused by adenovirus serotype 26.adenoviridae are rare causes of meningoencephalitis in both immunocompetent and immunocompromised hosts. in this article the authors report a case of adenoviral meningoencephalitis caused by serotype 26 and its identification, not described previously, in cerebrospinal fluid (csf) by pcr and brain tissue by immunohistochemical staining.200616877305
ad26.cov2.s protects syrian hamsters against g614 spike variant sars-cov-2 and does not enhance respiratory disease.previously we have shown that a single dose of recombinant adenovirus serotype 26 (ad26) vaccine expressing a prefusion stabilized sars-cov-2 spike antigen (ad26.cov2.s) is immunogenic and provides protection in syrian hamster and non-human primate sars-cov-2 infection models. here, we investigated the immunogenicity, protective efficacy, and potential for vaccine-associated enhanced respiratory disease (vaerd) mediated by ad26.cov2.s in a moderate disease syrian hamster challenge model, using t ...202133741993
low-dose ad26.cov2.s protection against sars-cov-2 challenge in rhesus macaques.we previously reported that a single immunization with an adenovirus serotype 26 (ad26) vector-based vaccine expressing an optimized sars-cov-2 spike (ad26.cov2.s) protected rhesus macaques against sars-cov-2 challenge. in this study, we evaluated the immunogenicity and protective efficacy of reduced doses of ad26.cov2.s. 30 rhesus macaques were immunized once with 1×10 11 , 5×10 10 , 1.125×10 10 , or 2×10 9 vp ad26.cov2.s or sham and were challenged with sars-cov-2 by the intranasal and intratr ...202133532782
low-dose ad26.cov2.s protection against sars-cov-2 challenge in rhesus macaques.we previously reported that a single immunization with an adenovirus serotype 26 (ad26)-vector-based vaccine expressing an optimized sars-cov-2 spike (ad26.cov2.s) protected rhesus macaques against sars-cov-2 challenge. to evaluate reduced doses of ad26.cov2.s, 30 rhesus macaques were immunized once with 1 × 1011, 5 × 1010, 1.125 × 1010, or 2 × 109 viral particles (vp) ad26.cov2.s or sham and were challenged with sars-cov-2. vaccine doses as low as 2 × 109 vp provided robust protection in bronch ...202134133941
single-shot ad26 vaccine protects against sars-cov-2 in rhesus macaques.a safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (sars-cov-2) may be required to end the coronavirus disease 2019 (covid-19) pandemic1-8. for global deployment and pandemic control, a vaccine that requires only a single immunization would be optimal. here we show the immunogenicity and protective efficacy of a single dose of adenovirus serotype 26 (ad26) vector-based vaccines expressing the sars-cov-2 spike (s) protein in non-human primates. fifty-two rhesus macaq ...202032731257
progress in the development of an adenovirus 26 vector platform for hiv vaccines.evaluation of: baden lr, walsh sr, seaman ms et al. first-in-human evaluation of the safety and immunogenicity of a recombinant adenovirus serotype 26 hiv-1 env vaccine (ipcavd 001). j. infect. dis. 207(2), 240-247 (2013). a novel replication-deficient recombinant adenovirus serotype 26 vector expressing the envelope protein of a clade a hiv type 1 was evaluated in a group of 60 healthy human volunteers. three different doses of the recombinant adenovirus vector were used to assess its safety an ...201323659296
adenovirus serotype 26 and 35 vectors induce simian immunodeficiency virus-specific t lymphocyte responses in foreskin in rhesus monkeys.foreskin is the principal site of heterosexual hiv-1 infection in men. however, little is known about hiv-1-specific immune responses or inflammation in foreskin. to the best of our knowledge, no previous studies have assessed immune responses to candidate hiv-1 vaccines in foreskin. using the rhesus monkey model, we show that intramuscular immunization with adenovirus serotype 26 and 35 vectors expressing siv antigens elicited durable siv gag-specific cd4(+) and cd8(+) t cell responses in fores ...201424429370
induction of hiv-1-specific mucosal immune responses following intramuscular recombinant adenovirus serotype 26 hiv-1 vaccination of humans.defining mucosal immune responses and inflammation to candidate human immunodeficiency virus type 1 (hiv-1) vaccines represents a current research priority for the hiv-1 vaccine field. in particular, it is unclear whether intramuscular immunization can elicit immune responses at mucosal surfaces in humans.201525165165
protective efficacy of adenovirus/protein vaccines against siv challenges in rhesus monkeys.preclinical studies of viral vector-based hiv-1 vaccine candidates have previously shown partial protection against neutralization-resistant virus challenges in rhesus monkeys. in this study, we evaluated the protective efficacy of adenovirus serotype 26 (ad26) vector priming followed by purified envelope (env) glycoprotein boosting. rhesus monkeys primed with ad26 vectors expressing sivsme543 env, gag, and pol and boosted with as01b-adjuvanted sivmac32h env gp140 demonstrated complete protectio ...201526138104
assessment of the safety and immunogenicity of 2 novel vaccine platforms for hiv-1 prevention: a randomized trial.a prophylactic hiv-1 vaccine is a global health priority.201626833336
new concepts in hiv-1 vaccine development.with 2 million people newly infected with hiv-1 in 2014, an effective hiv-1 vaccine remains a major public health priority. hiv-1 vaccine efficacy trials in humans, complemented by active and passive immunization studies in non-human primates, have identified several key vaccine-induced immunological responses that may correlate with protection against hiv-1 infection. potential correlates of protection in these studies include v2-specific, polyfunctional, and broadly neutralizing antibody respo ...201627268856
ad26/mva therapeutic vaccination with tlr7 stimulation in siv-infected rhesus monkeys.the development of immunologic interventions that can target the viral reservoir in hiv-1-infected individuals is a major goal of hiv-1 research. however, little evidence exists that the viral reservoir can be sufficiently targeted to improve virologic control following discontinuation of antiretroviral therapy. here we show that therapeutic vaccination with ad26/mva (recombinant adenovirus serotype 26 (ad26) prime, modified vaccinia ankara (mva) boost) and stimulation of tlr7 (toll-like recepto ...201627841870
attenuation of replication-competent adenovirus serotype 26 vaccines by vectorization.replication-competent adenovirus (rcad)-based vaccine vectors may theoretically provide immunological advantages over replication-incompetent ad vectors, but they also raise additional potential clinical and regulatory issues. we produced replication-competent ad serotype 26 (rcad26) vectors by adding the e1 region back into a replication-incompetent ad26 vector backbone with the e3 or e3/e4 regions deleted. we assessed the effect of vectorization on the replicative capacity of the rcad26 vaccin ...201526376928
recombinant adenovirus serotype 26 (ad26) and ad35 vaccine vectors bypass immunity to ad5 and protect nonhuman primates against ebolavirus challenge.the use of adenoviruses (ad) as vaccine vectors against a variety of pathogens has demonstrated their capacity to elicit strong antibody and cell-mediated immune responses. adenovirus serotype c vectors, such as ad serotype 5 (ad5), expressing ebolavirus (ebov) glycoprotein (gp), protect completely after a single inoculation at a dose of 10(10) viral particles. however, the clinical application of a vaccine based on ad5 vectors may be hampered, since impairment of ad5 vaccine efficacy has been d ...201121325402
tlr4 ligands augment antigen-specific cd8+ t lymphocyte responses elicited by a viral vaccine vector.toll-like receptor (tlr) ligands are critical activators of innate immunity and are being developed as vaccine adjuvants. however, their utility in conjunction with viral vector-based vaccines remains unclear. in this study, we evaluated the impact of a variety of tlr ligands on antigen-specific cd8(+) t lymphocyte responses elicited by a recombinant adenovirus serotype 26 (rad26) vector expressing simian immunodeficiency virus gag in mice. the tlr3 ligand poly(i:c) suppressed gag-specific cellu ...201020631129
mosaic hiv-1 gag antigens can be processed and presented to human hiv-specific cd8+ t cells.polyvalent mosaic hiv immunogens offer a potential solution for generating vaccines that can elicit immune responses against genetically diverse viruses. however, it is unclear whether key t cell epitopes can be processed and presented from these synthetic ags and recognized by epitope-specific human t cells. in this study, we tested the ability of mosaic hiv immunogens expressed by recombinant, replication-incompetent adenovirus serotype 26 vectors to process and present major hiv clade b and c ...201121576505
evaluation of a mosaic hiv-1 vaccine in a multicentre, randomised, double-blind, placebo-controlled, phase 1/2a clinical trial (approach) and in rhesus monkeys (nhp 13-19).more than 1·8 million new cases of hiv-1 infection were diagnosed worldwide in 2016. no licensed prophylactic hiv-1 vaccine exists. a major limitation to date has been the lack of direct comparability between clinical trials and preclinical studies. we aimed to evaluate mosaic adenovirus serotype 26 (ad26)-based hiv-1 vaccine candidates in parallel studies in humans and rhesus monkeys to define the optimal vaccine regimen to advance into clinical efficacy trials.201830047376
mosaic hiv-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys.the worldwide diversity of hiv-1 presents an unprecedented challenge for vaccine development. antigens derived from natural hiv-1 sequences have elicited only a limited breadth of cellular immune responses in nonhuman primate studies and clinical trials to date. polyvalent 'mosaic' antigens, in contrast, are designed to optimize cellular immunologic coverage of global hiv-1 sequence diversity. here we show that mosaic hiv-1 gag, pol and env antigens expressed by recombinant, replication-incompet ...201020173752
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