Hongjun Bai
A5090782451- HIV Research and Treatment
- SARS-CoV-2 and COVID-19 Research
- vaccines and immunoinformatics approaches
- Animal Virus Infections Studies
- Protein Structure and Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Enzyme Structure and Function
- HIV/AIDS drug development and treatment
- Computational Drug Discovery Methods
- Mosquito-borne diseases and control
- Viral Infections and Vectors
- Glycosylation and Glycoproteins Research
- HIV/AIDS Research and Interventions
- Complement system in diseases
- Virology and Viral Diseases
- Viral gastroenteritis research and epidemiology
- Microbial Metabolic Engineering and Bioproduction
- Viral Infections and Immunology Research
- Viral Infections and Outbreaks Research
- Malaria Research and Control
- RNA and protein synthesis mechanisms
- Immune Cell Function and Interaction
- Platelet Disorders and Treatments
- Peptidase Inhibition and Analysis
- Wnt/β-catenin signaling in development and cancer
Walter Reed Army Institute of Research
2017-2025
Henry M. Jackson Foundation
2017-2025
National Cancer Institute
2013-2019
National Institutes of Health
2013-2019
Center for Cancer Research
2013-2019
University of Pennsylvania
2012-2013
MRC Laboratory of Molecular Biology
2013
Jining Traditional Chinese Medicine Hospital
2013
Peking University
2007-2010
Beijing National Laboratory for Molecular Sciences
2007-2010
The magnitude of the COVID-19 pandemic underscores urgency for a safe and effective vaccine. Many vaccine candidates focus on Spike protein, as it is targeted by neutralizing antibodies plays key role in viral entry. Here we investigate diversity seen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequences compare to sequence which most are based. Using 18,514 sequences, perform phylogenetic, population genetics, structural bioinformatics analyses. We find limited across...
Drugs against multiple targets may overcome the many limitations of single and achieve a more effective safer control disease. Numerous high-throughput experiments have been performed in this emerging field. However, systematic identification drug their best intervention requires knowledge underlying disease network calls for innovative computational methods that exploit structure dynamics. Here, we develop robust algorithm finding target optimal (MTOI) solutions network. MTOI identifies...
Therapeutic modulation of the complement system has become increasingly important in line with growing recognition role numerous diseases. Compstatin, a peptidic inhibitor that acts at central level cascade, is currently clinical evaluation but routes to improve its efficacy have not yet been fully explored. Here, we report improvements both inhibitory potency and pharmacokinetic parameters compstatin broaden applications. Selective modification N-terminus non-proteinogenic amino acids...
Inadequate control of the complement system is underlying or aggravating factor in many human diseases. Whereas treatment options that specifically target alternative pathway (AP) activation are considered highly desirable, no such option available clinic. In this study, we present a successful example protein engineering, guided by structural insight on regulator H (FH), yielding novel complement-targeted therapeutic (mini-FH) with clinical potential. Despite 70% reduction size, mini-FH...
Wnt signaling is one of the key regulators hepatocellular carcinoma (HCC) tumor progression. In addition to classical receptor frizzled (FZD), various coreceptors including heparan sulfate proteoglycans (HSPGs) are involved in activation. Glypican‐3 (GPC3) an HSPG that overexpressed HCC and functions as a coreceptor modulates cell proliferation. These features make GPC3 attractive target for liver cancer therapy. However, precise interaction how GPC3, Wnt, FZD cooperate with each other...
Despite rapid and ongoing vaccine therapeutic development, SARS-CoV-2 continues to evolve evade, presenting a need for next-generation diverse modalities. Here we show that nurse sharks immunized with recombinant receptor binding domain (RBD), RBD-ferritin (RFN), or spike protein ferritin nanoparticle (SpFN) immunogens elicit set of new antigen antibody (IgNAR) molecules target two non-overlapping conserved epitopes on the RBD. Representative shark variable NAR-Fc chimeras (ShAbs) targeting...
Abstract The repeat emergence of SARS-CoV-2 variants concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need develop next-generation vaccine candidates that confer broad protection. Here we describe antibody response induced by Spike Ferritin Nanoparticle (SpFN) candidate adjuvanted Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal directed against Receptor Binding Domain (RBD),...
In the Antibody Mediated Prevention (AMP) trials (HVTN 704/HPTN 085 and HVTN 703/HPTN 081), prevention efficacy (PE) of monoclonal broadly neutralizing antibody (bnAb) VRC01 (vs. placebo) against HIV-1 acquisition diagnosis varied according to Envelope (Env) neutralization sensitivity VRC01, as measured by 80% inhibitory concentration (IC80). Here, we performed a genotypic sieve analysis, complementary approach gaining insight into correlates protection that assesses how PE varies with...
ABSTRACT We present the assessment of predictions for Template‐Free Modeling in CASP10 and a report on first ROLL experiment wherein are collected year round review at regular CASP season. Models were clustered so that duplicated or very similar ones grouped together represented by one model cluster. The representatives then compared with targets using GDT_TS, QCS, three additional superposition‐independent score functions newly developed CASP10. For each target, top 15 pooled to form...
Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 genomes sampled from 27 and 20 placebo recipients found intra-host diversity was significantly lower (P ≤ 0.04, Q-values 0.09) Gag, Pol, Vif envelope glycoprotein gp120 (Env-gp120). Furthermore, Env-gp120 were more...
SUMMARY SARS-CoV-2 is a zoonotic virus that has caused pandemic of severe respiratory disease—COVID-19— within several months its initial identification. Comparable to the first SARS-CoV, this novel coronavirus’s surface Spike (S) glycoprotein mediates cell entry via human ACE-2 receptor, and, thus, principal target for development vaccines and immunotherapeutics. Molecular information on S remains limited. Here we report crystal structure receptor-binding-domain (RBD) at highest resolution...
ABSTRACT Knowledge of HIV-1 global sequence diversity is critical for developing an effective prophylactic against infection. We developed the Hervé platform to analyze and visualize trends in diversification. Using Hervé, we analyzed 4,830 Env, 4,407 Gag, 3,002 Pol publicly available independent sequences corresponding subtypes A1, A6, B, C, D, F1, G circulating recombinant forms (CRFs) 01_AE, 02_AG, 07_BC; were sampled between 1980 2020 from 82 countries. diversified with a median 1.82...
Harnessing CD8+ T cell responses is being explored to achieve HIV remission. Although HIV-specific cells become dysfunctional without treatment, antiretroviral therapy (ART) partially restores their function. However, the extent of this recovery under long-term ART less understood.We analyzed differentiation status and function after initiated in acute or chronic infection ex vivo upon vitro recall.ART initiation any stage promoted persistence long-lived with high expansion (P<0·0008)...
Characterization of MAbs against SARS-CoV-2, elicited through vaccination or natural infection, has provided vital immunotherapeutic options for curbing the COVID-19 pandemic and supplied critical insights into SARS-CoV-2 escape, transmissibility, mechanisms viral inactivation. Neutralizing that target RBD but do not block ACE2 binding are particular interest because epitopes well conserved within sarbecoviruses targeting this area demonstrate cross-reactivity.
Given the continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants concern (VoCs), immunotherapeutics that target conserved epitopes on spike (S) glycoprotein have therapeutic advantages. Here, we report crystal structure SARS-CoV-2 S receptor-binding domain (RBD) at 1.95 Å and describe flexibility distinct conformations angiotensin-converting enzyme (ACE2)-binding site. We identify a set SARS-CoV-2-reactive monoclonal antibodies (mAbs) with broad RBD...
Infusion of the broadly neutralizing antibody VRC01 has been evaluated in individuals chronically infected with HIV-1. Here, we studied how infusions affected viral rebound after cessation antiretroviral therapy (ART) 18 acutely treated and durably suppressed individuals. Viral occurred all individuals, yet modestly delayed participants who showed a faster decay serum rebounded more rapidly. Participants strains most sensitive to or epitope motifs similar known VRC01-susceptible later. Upon...
HIV-1 envelope broadly neutralizing antibodies represent a promising component of cure strategies. To evaluate the therapeutic efficacy combination monoclonal (mAbs) in rigorous nonhuman primate model, we tested different combinations simian immunodeficiency virus (SIV) mAbs SIVmac251-infected rhesus macaques. Antiretroviral therapy-suppressed animals received anti-SIV targeting multiple Env epitopes spanning analytical treatment interruption (ATI) 3 groups (n = 7 each): i) no mAb; ii) 4-mAb...
The Janssen Ebola virus (EBOV) vaccine consists of the adenovirus type 26 vector encoding EBOV glycoprotein (GP) (Ad26.ZEBOV) and modified vaccinia Ankara (MVA) GP from EBOV, Sudan virus, Marburg nucleoprotein Tai Forest (MVA-BN-Filo) administered 8 weeks later. We conducted a systems immunology analysis antibody-mediated cellular immune responses induced after two immunizations with either used first. response to vaccination was specific defined by high antibody binding, Fc effector,...
Abstract In the ENSEMBLE randomized, placebo-controlled phase 3 trial (NCT04505722), estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe–critical COVID-19. SARS-CoV-2 Spike sequences were determined from 484 and 1,067 placebo recipients who acquired this set of prespecified analyses, we show that in Latin America, VE significantly lower Lambda vs. Reference non-Lambda [family-wise error rate (FWER) p < 0.05]. differed by residue match mismatch...
An effective HIV-1 vaccine must elicit broadly neutralizing antibodies (bnAbs) against highly diverse Envelope glycoproteins (Env). Since Env with the longest hypervariable (HV) loops is more resistant to cognate bnAbs than shorter HV loops, we redesigned for updated consensus sequences of subtypes B and C CRF01_AE. Using modeling AlphaFold2, reduced length V1, V2, V5 while maintaining integrity structure glycan shield, modified V4 loop. Spacers are designed limit strain-specific targeting....
Abstract Elucidating kinetic processes of protein–protein interactions (PPI) helps to understand how basic building blocks affect overall behavior living systems. In this study, we used structure‐based properties build predictive models for constants PPI. A highly diverse PPI dataset, interaction data and structures (PPKIDS), was built. PPKIDS contains 62 with complex measured experimentally. The influence structural on kinetics studied using 35 features, describing different aspects...
Zika virus (ZIKV) is an emerging pathogen that causes devastating congenital defects. The overlapping epidemiology and immunologic cross-reactivity between ZIKV dengue (DENV) pose complex challenges to vaccine design, given the potential for antibody-dependent enhancement of disease. Therefore, classification ZIKV-specific antibody targets notable value. From a ZIKV-infected rhesus macaque, we identify ZIKV-reactive B cells isolate potent neutralizing monoclonal antibodies (mAbs) with no...