A Phase 1b Randomized Double-Blind Clinical Trial to Examine Whether Polytopic Administration of VRC rAd5 Gag-pol/Env A/B/C Vaccine Enhances HIV-Specific Cellular Immune Responses in Humans

The purpose of this study is to evaluate the immune response to the Vaccine Research Center (VRC) rAd5 HIV vaccine when the vaccine components are administered in three different ways, in healthy, HIV-uninfected adults.

开始日期2011-12-01

申办/合作机构

National Institute of Allergy & Infectious Diseases

100 项与 HIV vaccine rAd5-gag-pol VRC(GenVec) 相关的临床结果

登录后查看更多信息

100 项与 HIV vaccine rAd5-gag-pol VRC(GenVec) 相关的转化医学

登录后查看更多信息

100 项与 HIV vaccine rAd5-gag-pol VRC(GenVec) 相关的专利（医药）

登录后查看更多信息

项与 HIV vaccine rAd5-gag-pol VRC(GenVec) 相关的文献（医药）

2023-10-01·Current opinion in immunology

An easy pill to swallow: oral recombinant vaccines for the 21st century.

Review

作者: Tucker, Sean N ; Braun, Molly R ; Flitter, Becca A ; Sun, William

Oral vaccines have a distinctive advantage of stimulating immune responses in the mucosa, where numerous pathogens gain entry and cause disease. Although various efforts have been attempted to create recombinant mucosal vaccines that provoke strong immunogenicity, the outcomes in clinical trials have been weak or inconsistent. Therefore, next-generation mucosal vaccines are needed that are more immunogenic. Here, we discuss oral vaccines with an emphasis on a next-generation mucosal vaccine that utilizes a nonreplicating human recombinant adenovirus type-5 (rAd5) vector. Numerous positive clinical results investigating oral rAd5 vaccines are reviewed, with a summary of the immunogenicity and efficacy results for specific vaccine indications of influenza, norovirus, and SARS-CoV-2. The determination of correlates of protection for oral vaccination and the potential impact this novel vaccine formulation may have on disease transmission are also discussed. In summary, successful oral vaccination can be accomplished and would have major public health benefits if approved.

2023-03-01·International Immunopharmacology

An oral NoV-rAd5 vaccine with built-in dsRNA adjuvant elicits systemic immune responses in mice

Article

作者: Mao, Tongyao ; Wang, Jindong ; Sun, Xiaoman ; Duan, Zhaojun ; Li, Jinsong ; Ma, Yalin ; Peng, Rui

Norovirus (NoV) is an enteric pathogen notorious for causing epidemics of acute gastroenteritis. An effective vaccine against NoV is therefore urgently needed. A short double-stranded RNA (dsRNA) has been described that acts as a retinoic-acid-inducible gene-I agonist to induce the production of type I interferon; it also exhibits adjuvant activity. Using built-in dsRNA of different lengths (DS1 and DS2), we developed a recombinant adenovirus 5 (rAd5) expressing NoV VP1, and evaluated its immunogenicity following oral administration in a mouse model. An in vitro study demonstrated that the dsRNA adjuvants significantly enhanced VP1 protein expression in infected cells. The oral administration of both rAd5-VP1-DS vaccines elicited high serum levels of VP1-specific IgG and blocking antibodies, as well as strong and long-lasting mucosal immunity. There was no apparent difference in immunostimulatory effects in immunised mice between the two dsRNA adjuvants. This study indicates that an oral NoV-rAd5 vaccine with a built-in dsRNA adjuvant may be developed to prevent NoV infection in humans.

2021-04-01·Glia1区 · 医学

Programmed death ligand‐1 induction restrains the cytotoxic T lymphocyte response against microglia

1区 · 医学

Article

作者: Lokensgard, James R. ; Chauhan, Priyanka ; Prasad, Sujata ; Hu, Shuxian ; Sheng, Wen S.

AbstractMicroglial cells are the main reservoir for HIV‐1 within the brain and potential exists for negative immune checkpoint blockade therapies to purge this viral reservoir. Here, we investigated cytolytic responses of CD8+ T lymphocytes against microglia loaded with peptide epitopes. Initially, flow cytometric analysis demonstrated efficient killing of HIV‐1 p24 AI9 or YI9 peptide‐loaded splenocytes in MHC‐matched recipients. Cytolytic killing of microglia was first demonstrated using ovalbumin (OVA) as a model antigen for in vitro cytotoxic T lymphocyte (CTL) assays. Peptide‐loaded primary microglia obtained from programmed death ligand (PD‐L) 1 knockout (KO) animals showed significantly more killing than cells from wild‐type (WT) animals when co‐cultured with activated CD8+ T‐cells isolated from rAd5‐OVA primed animals. Moreover, when peptide loaded‐microglial cells from WT animals were treated with neutralizing α‐PD‐L1 Ab, significantly more killing was observed compared to either untreated or IgG isotype‐treated cells. Most importantly, significantly increased in vivo killing of HIV‐1 p24 YI9 peptide‐loaded microglia from PD‐L1 KO animals, as well as AI9 peptide‐loaded BALB/c microglial cells treated with α‐PD‐L1, was observed within brains of rAd5‐p24 primed‐CNS boosted C57BL/6 or BALB/c mice, respectively. Finally, ex vivo responses of brain CD8+ T‐cells in response to AI9 stimulation showed significantly increased IFN‐γ and IL‐2 production when treated with α‐PD‐1 Abs. Greater proliferation of CD8+ T‐cells from the brain was also observed following blockade. Taken together, these studies demonstrate that PD‐L1 induction on microglia restrains CTL responses and indicate that immune checkpoint blockade targeting this pathway may be beneficial in clearing viral brain reservoirs.

100 项与 HIV vaccine rAd5-gag-pol VRC(GenVec) 相关的药物交易

登录后查看更多信息