Designing an effective HIV-1 envelope glycoprotein (Env) immunogen for elicitation of broadly neutralizing antibodies (bNAbs) is a challenging task because of the high sequence diversity, heavy glycosylation, and inherent meta-stability of Env. Based on the antigenic profile of recently isolated bNAbs, the rational approach to immunogen design is to make a stable version of the Env trimer, which mimics the native trimeric Env present on the viral surface. The SOSIP.664 form of a clade A Env, BG505, yields a homogeneous and well ordered prefusion trimeric form, which maintains structural integrity and desired antigenicity. Following the same approach, we attempted to stabilize a naturally occurring efficiently cleaved clade C Env, namely 4-2.J41, isolated from an Indian patient. Although the SOSIP form of 4-2.J41 failed to produce reasonably well ordered trimers, the 4-2.J41.SOSIP.664 Env could be stabilized in a native-like trimeric form by swapping a domain from BG505 Env to 4-2.J41 Env. Using various biochemical and biophysical means we confirmed that this engineered Env is cleaved, trimeric, and it retains its native-like quaternary conformation exposing mostly broadly neutralizing epitopes. Moreover, introduction of a disulfide bond in the bridging sheet region further stabilized the closed conformation of the Env. Thus, our 4-2.J41.SOSIP.664 Env adds to the increasing pool of potential immunogens for a HIV-1 vaccine, particularly for clade C, which is the most prevalent in India and many other countries. Besides, the approach used to stabilize the 4-2.J41 Env may be used successfully with Envs from other HIV-1 strains as well. Additionally, a soluble native trimeric form of an efficiently cleaved membrane-bound Env, 4-2.J41, may be beneficial for immunization studies using various prime-boost strategies.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2qYF3eE
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Differential Effect of Hypoalbuminemia on Hypoglycemia on Type 2 Diabetes Patients Treated with Insulin Glargine 300 U/ml and Insulin Deglud...
-
Southeast China is frequently hit by tropical cyclones (TCs) with significant economic and health burdens each year. However, there is a lac...
-
Abstract BACE1 is an indispensable enzyme for generating β-amyloid peptides, which are excessively accumulated in brains of Alzheimer'...
-
HIV Positivity and Referral to Treatment Following Testing of Partners and Children of PLHIV Index Patients in Public Sector Facilities in S...
-
Upon recognition of bacterial pathogen by pattern recognition receptors, cells are activated to produce pro-inflammatory cytokines and type ...
-
In the Original Investigation titled “Yield Strength Testing in Human Cadaver Nasal Septal Cartilage and L-Strut Constructs,” published in t...
-
Purpose: To summarize the clinical, radiographic, and intraoperative characteristics of isolated neurofibromas of the orbit (INFO) in the li...
-
International Journal of Environmental Research and Public Health, IJERPH, Vol. 16, Pages 3884:... International Journal of Environmental Re...
-
Metformin is the first-line drug in the treatment of type 2 diabetes. In addition to its hypoglycemic effect, metformin has an anti-inflamma...
-
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2phMgBA via IFTTT
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου