Dan H Barouch

..ENVA.01), are reported concurrently with this article. Here, we characterize in greater detail the humoral and cellular immune responses elicited by Ad26.ENVA.01 in humans...

..Overall, the data suggest that vaccines and microbicides are complementary techniques that may protect better when used together than separately...

..A novel chimeric Ad5 vector in which both the hexon HVRs and the fiber knob were exchanged nearly completely evaded Ad5-specific NAbs both in vitro and in vivo...

..These data demonstrate the proof-of-concept that optimized HIV-1 vaccine candidates can block acquisition of stringent, heterologous, neutralization-resistant virus challenges in rhesus monkeys...

..Polyvalent mosaic antigens therefore represent a promising strategy to expand cellular immunologic vaccine coverage for genetically diverse pathogens such as HIV-1...

..Moreover, these studies suggest that using Ad vectors derived from immunologically distinct serotypes may be an effective and general strategy to overcome the suppressive effects of pre-existing anti-Ad immunity...

..We review the current state of the HIV-1 vaccine field and outline strategies that are being explored to overcome these roadblocks...

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..Inclusion of Env resulted in improved control of peak and set point SIV RNA levels following challenge. In contrast, DNA vaccine priming did not further improve the protective efficacy of rAd5HVR48 vectors in this system...

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..In this review, we describe progress in the development of rAd vector-based vaccines with a focus on human immunodeficiency virus type 1...

..Here I review key challenges and future prospects in the quest to develop a prophylactic HIV-1 vaccine...

..These data demonstrate that plasmid cytokines can markedly improve the immunogenicity of DNA prime-viral vector boost vaccine strategies and can partially compensate for antivector immunity...

..In this review, current strategies to develop and optimize gene-based vaccines are described, with an emphasis on novel approaches to improve plasmid DNA vaccines and recombinant adenovirus vector-based vaccines...

..These data inform the clinical development of alternative serotype rAd vaccine vectors in the developing world...

..These data suggest that CTL exert selective pressure on viral replication and that viral escape from CTL may be a limitation of CTL-based AIDS vaccine strategies...

..These vectors are being explored as potential vaccine candidates for a variety of pathogens. This review summarizes current efforts to develop rAd vector-based vaccines for HIV-1...

..Therefore, administration of ADV5-based vectors in DNA-primed subjects may be a preferred use of this vaccine modality for generating long-term immune protection...

..Synergistic recruitment and expansion of DCs in vivo may prove a practical strategy for overcoming this limitation and potentiating immune responses to vaccines as well as other immunotherapeutic strategies...

..These studies substantially expand the portfolio of rare serotype rAd vectors that may prove useful as vaccine vectors for the developing world...

..Thus, i.m. vaccination can overcome immune compartmentalization and generate robust mucosal CD8(+) T lymphocyte memory. These data demonstrate that the systemic and mucosal immune systems are highly coordinated following vaccination...

..Moreover, qualitative differences in cellular immune responses may prove critical in determining the overall potency of heterologous rAd prime-boost regimens...

..Together, these studies suggest that a multi-dose vaccine regimen utilizing up to four inoculations of MVA generates robust and durable antibody-mediated immunity comparable to that elicited by replication-competent VV...

..Persisting clinical protection in vaccinated and challenged monkeys is thus correlated with a preserved capacity of the peripheral blood central memory CD4+ T cells to express this important immunomodulatory cytokine...

..These findings have important implications for the development of next-generation T-cell-based vaccine candidates for HIV-1...

..These studies suggest a potential strategy for engineering novel Ad5 vectors to evade dominant Ad5-specific NAbs...

..These data indicate that viral escape from CTL recognition may be a major limitation of the CTL-based AIDS vaccines that are likely to be administered to large human populations over the next several years...

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..These data indicate that prior vaccination can increase the breadth of the CTL response that evolves after an AIDS virus infection...

..Moreover, these studies demonstrate that capsid chimeric rAd vectors can be constructed to combine beneficial immunologic and serologic properties of different Ad serotypes...

..Novel adenovirus vectors that are currently being developed to circumvent the problem of preexisting anti-Ad5 immunity should therefore be designed to evade both humoral and cellular Ad5-specific immune responses...

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..This study, therefore, indicates that the steady-state memory, rather than the peak effector vaccine-elicited T lymphocyte responses, may be the critical immune correlate of protection for a CTL-based HIV vaccine...

..These findings have implications for the design and interpretation of HIV-1 vaccine efficacy studies...

..Moreover, an AIDS vaccine that confers protection against clinical disease evolution in this experimental model also preserves the functional capacity of these CTL to produce both IL-2 and TNF-alpha...

..Moreover, these findings suggest the potential utility of TLR4 ligands as adjuvants for rAd vector-based vaccines...

..This strategy could therefore be explored as a potential method to enhance DNA vaccine immunogenicity in humans...

..Such chimaeric viral vectors may have important practical implications for vaccination and gene therapy...

..These findings challenge the hypothesis that activated Ad5-specific T lymphocytes were the cause of the potential enhanced HIV-1 susceptibility in the STEP study...

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..This real-time PCR technique for evaluating CTL epitope mutations may prove to be a useful tool for monitoring the genetic drift of human immunodeficiency virus and SIV in infected individuals...

..Moreover, these studies show that different subsets of professional APC can selectively modulate DNA vaccine-elicited T lymphocyte responses...

..These studies suggest that multiepitope plasmid DNA vaccine-based prime-boost regimens can efficiently prime for CTL responses of increased breadth and magnitude, although they do not overcome predicted hierarchies of immunodominance...

..These results demonstrate that bicistronic DNA vaccines containing GM-CSF elicit remarkably potent CD4(+) T cell responses and suggest that optimal Th cell priming requires the precise temporal and spatial codelivery of Ag and GM-CSF...

..These findings suggest that immunization with centralized genes is a promising vaccine strategy for developing a global vaccine for HIV-1 as well as vaccines for other genetically diverse viruses...

..m. or i.n. rAd immunization. Our findings indicate that the anatomic microenvironment of antigen expression critically impacts the phenotype and trafficking of antigen-specific CD8(+) T lymphocytes...

..These data contribute to our understanding of Ad26 as a candidate vaccine vector...

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..Together, these data suggest that a compensatory mutation is selected for in SHIV strain 89.6P to facilitate the escape of that virus from CTL recognition of the dominant p11C, C-M epitope...

..Vaccine-elicited T(EM) responses at mucosal surfaces may prove critical for affording protection against invading pathogens at the mucosal portals of entry...

..These studies also suggest that rAd vectors warrant further assessment as candidate subunit smallpox vaccines...

..Combining in vivo EP with plasmid chemokine adjuvants that similarly recruited APCs to the injection site, however, did not result in synergy...

..We then describe vaccine strategies that have been explored and discuss the evidence suggesting that cellular immune responses elicited by novel vaccine modalities may attenuate clinical disease caused by HIV-1...

..These results, which demonstrate that there are relevant immunologic differences between monomers and high-quality envelope trimers, have important implications for HIV-1 vaccine development...

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..These data have important implications for the development of novel vectors for both vaccines and gene therapy...

..clinicaltrials.gov NCT00125099)..

..We observed a clear age dependence of Ad5-specific neutralizing antibody titers. These data will help to guide the development of Ad vector-based vaccines for human immunodeficiency virus type 1 and other pathogens...

..These data suggest the importance of including Gag in an HIV-1 vaccine in which virologic control is desired...

..These results suggest the potential of an accelerated heterologous rAd prime-boost regimen as a candidate HIV-1 vaccine for newborns...

..These data suggest that antigen-independent factors contribute to the immunodominance patterns of vaccine-elicited cellular immune responses...

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..Stimulation of multiple innate immune mechanisms may prove a generalizable property of potent vaccines, and this strategy could be harnessed in the development of next-generation vaccine vectors and adjuvants...

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..Here, we review recent advances in our understanding of cytokine biology, T-lymphocyte differentiation, and potential applications of plasmid cytokines in the rational design of improved vaccines...

..34 or 0.36, respectively. These findings call into question the premise that CCL3L CNV is important in HIV/SIV pathogenesis...

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..These data suggest that viral escape from CTL may prove to be a significant limitation of the current generation of CTL-based AIDS vaccines...

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..Trichosporonosis is an emerging invasive fungal infection in immunosuppressed patients; a case of disseminated infection caused by Trichosporon loubieri presented confirms its role as a human pathogen...

..SIVGag vaccine. These data demonstrate the potential of a replication deficient human group D adenoviral vector for vaccination purposes...

..These data suggest that although effector T cells can limit viral replication, they are not able to assist humoral immunity to prevent the establishment of initial infection...

..An immunogen that elicits broadly reactive neutralizing antibodies, however, has yet to be developed...

..Nevertheless, these data suggest the potential utility of heterologous rAd prime-boost vaccine regimens using vectors derived from rare human Ad serotypes...

..Further, the addition of a molecular IL-2 adjuvant augments this DNA vaccine...

..Liver infection by the FX-Ad5 complex is mediated through a heparin-binding exosite in the FX serine protease domain. This study reveals an unanticipated function for hexon in mediating liver gene transfer in vivo...

..In this proposal, we will assess the impact of HIV-1 envelope conformation on the profile of elicited neutralizing antibody responses. ..

..In this proposal, we will assess the impact of HIV-1 envelope conformation on the profile of elicited neutralizing antibody responses. ..

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..The long-term objectives of these studies are to develop novel vaccine regimens that recruit APCs to the site of inoculation in animal models and to consider advancing the most promising strategies into clinical trials. ..

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..Raphael Dolin, Dean for Clinical Programs, Harvard Medical School, will guide Dr. Barouch's development as an independent investigator. In addition, a committee of distinguished scientists will oversee his progress toward independence. ..

..Within the two-year time frame of this award, sufficient data will be generated with candidate chimeric rAd vaccines to justify further vaccine/challenge studies in rhesus monkeys. ..