Characterization of the Innate Immune Response to Candidate HIV Vaccines, an Ancillary Study to HVTN 205
HVTN 908 is a sub study of the HIV vaccine trial, HVTN 205. The purpose of this sub study is to better understand how a person's immune system responds to vaccines, particularly HIV vaccines. More specifically, researchers will determine whether early responses in the immune system help predict strong and long-lasting immunity.
作者: Catherine H Schein ; Corri B Levine ; Susan L F McLellan ; Surendra S Negi ; Werner Braun ; Stephen C Dreskin ; Elizabeth S Anaya ; Jurgen Schmidt
There is an urgent need for inexpensive, rapid and specific antigen-based assays to test for vaccine efficacy and detect infection with SARS-CoV-2 and its variants. We have identified a small, synthetic protein (JS7), representing a region of maximum variability within the receptor binding domain (RBD), which binds antibodies in sera from nine patients with PCR-verified COVID-19 of varying severity. Antibodies binding to either JS7 or the SARS-CoV-2 recombinant RBD, as well as those that disrupt binding between a fragment of the ACE2 receptor and the RBD, are proportional to disease severity and clinical outcome. Binding to JS7 was inhibited by linear peptides from the RBD interface with ACE2. Variants of JS7, such as E484 K or N501Y, can be quickly synthesized in a pure form in large quantities by automated methods. JS7 and related synthetic antigens can provide a basis for specific diagnostics for SARS-CoV-2 infections.
2019-07-01·Pesticide biochemistry and physiology2区 · 生物学
Molecular basis of resistance to ACCase-inhibiting herbicide cyhalofop-butyl in Chinese sprangletop (Leptochloa chinensis (L.) Nees) from China.
2区 · 生物学
作者: Wei Deng ; Jingxuan Cai ; Jingyun Zhang ; Yueyang Chen ; Yongrui Chen ; Yingjie Di ; Shuzhong Yuan
Chinese sprangletop (Leptochloa chinensis (L.) Nees) is one of the most troublesome grass weeds in rice in China. Seven suspected cyhalofop-butyl-resistant L. chinensis populations were collected from different rice fields with a history of cyhalofop-butyl use. The level of resistance and resistance mechanisms in seven populations were studied. Dose-response tests indicated that five populations (JS3, JS4, JS6, JS7 and JS8) had evolved high-level resistance (26.9 to 123.0-fold) to cyhalofop-butyl compared with the susceptible (S) population, and other two populations (JS2 and JS5) were still sensitive to the herbicide. Two acetyl-coenzyme A carboxylase (ACCase) genes were cloned from each population, and three different ACCase mutations (Ile-1781-Leu, Trp-1999-Cys, and Trp-2027-Cys) in ACCase2 gene were determined in different resistant (R) populations. In addition, no resistance-conferring mutations was detected in the R population (JS7), and ACCase gene expression was similar between the S and R populations. Thus, non-target-site resistance mechanisms may be involved in the JS7 population. Moreover, the patterns of cross-resistance of JS6 (Ile-1781-Leu), JS4 (Trp-1999-Cys), JS8 (Trp-2027-Cys), and JS7 (unknown resistance mechanisms) populations to other ACCase-inhibiting herbicides were determined. The JS6 and JS8 populations showed resistance to fenoxaprop-P-ethyl, metamifop, clethodim and pinoxaden, the JS4 population was resistant to fenoxaprop-P-ethyl, metamifop and pinoxaden, and the JS7 population had resistance only to fenoxaprop-P-ethyl and metamifop. These results indicated the diversity of the target-site mutations in ACCase gene of L. chinensis, and provide a better understanding of cross-resistance in L. chinensis, which would be helpful for the management of cyhalofop-butyl-resistant L. chinensis.
2014-07-01·Journal of Infectious Diseases2区 · 医学
Specificity and 6-month durability of immune responses induced by DNA and recombinant modified vaccinia ankara vaccines expressing HIV-1 virus-like particles
2区 · 医学
作者: Goepfert, Paul A. ; Elizaga, Marnie L. ; Seaton, Kelly ; Tomaras, Georgia D. ; Montefiori, David C. ; Sato, Alicia ; Hural, John ; DeRosa, Stephen C. ; Kalams, Spyros A. ; McElrath, M. Juliana ; Keefer, Michael C. ; Baden, Lindsey R. ; Lama, Javier R. ; Sanchez, Jorge ; Mulligan, Mark J. ; Buchbinder, Susan P. ; Hammer, Scott M. ; Koblin, Beryl A. ; Pensiero, Michael ; Butler, Chris ; Moss, Bernard ; Robinson, Harriet L.
Clade B DNA and recombinant modified vaccinia Ankara (MVA) vaccines producing virus-like particles displaying trimeric membrane-bound envelope glycoprotein (Env) were tested in a phase 2a trial in human immunodeficiency virus (HIV)-uninfected adults for safety, immunogenicity, and 6-month durability of immune responses.
A total of 299 individuals received 2 doses of JS7 DNA vaccine and 2 doses of MVA/HIV62B at 0, 2, 4, and 6 months, respectively (the DDMM regimen); 3 doses of MVA/HIV62B at 0, 2, and 6 months (the MMM regimen); or placebo injections.
At peak response, 93.2% of the DDMM group and 98.4% of the MMM group had binding antibodies for Env. These binding antibodies were more frequent and of higher magnitude for the transmembrane subunit (gp41) than the receptor-binding subunit (gp120) of Env. For both regimens, response rates were higher for CD4(+) T cells (66.4% in the DDMM group and 43.1% in the MMM group) than for CD8(+) T cells (21.8% in the DDMM group and 14.9% in the MMM group). Responding CD4(+) and CD8(+) T cells were biased toward Gag, and >70% produced 2 or 3 of the 4 cytokines evaluated (ie, interferon γ, interleukin 2, tumor necrosis factor α, and granzyme B). Six months after vaccination, the magnitudes of antibodies and T-cell responses had decreased by <3-fold.
DDMM and MMM vaccinations with virus-like particle-expressing immunogens elicited durable antibody and T-cell responses.