Hongying Duan (Holdsworth), M.D., Ph.D. (She/Her/Hers)
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Major Areas of Research
- HIV vaccine development and evaluation
- Animal models for HIV, Lassa, COVID-19 vaccine development
- B cell and T cell analysis, antibody development and characterization
1. Elicitation and maturation of VRC01-class antibodies in transgenic mouse models, which allows a germline human IGHV1-2*02 segment to undergo normal V(D)J recombination and, thereby, leads to the generation of peripheral B cells that express a highly diverse repertoire of VRC01-related receptors. A strong VRC01-class predicted germline precursor binder, eOD-GT8 60mer, was able to elicit and enrich VRC01-class antibodies in this mouse model.
2. Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires with sequential immunization. The serum from the stepwise immunized mice exhibited cross-strain neutralizing activities and the mutation frequency of both the IGHV1-2*02 IgH and VRC01 IgL chains steadily increased.
3. Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies. A substantial portion of eOD-GT8-elicited antibodies target non-CD4bs epitopes, potentially limiting its efficacy. To mask irrelevant epitopes, we introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 and evaluated the mutants in a VRC01-class mouse model. Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors.
4. Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization. The vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) develop, we identified, characterized, and tracked five neutralizing Ab lineages targeting the HIV-1-fusion peptide (FP) in vaccinated macaques over time. Genetic and structural analyses revealed two of these lineages to belong to a reproducible class capable of neutralizing up to 59% of 208 diverse viral strains. B cell analysis indicated that each of the five lineages was initiated and expanded by FP-carrier priming, with envelope (Env)-trimer boosts inducing cross-reactive neutralization.
5. Fusion Peptide Priming –Alone or in Cocktail with Env Trimer– Imprints Broad HIV-1-Neutralizing Responses with a Characteristic Early B Cell Signature. To optimize the immunization regimen and shorten the “neutralization-eclipse phase”, we analyzed plasma and antigen-specific B cells from 7 different immunization regimens in 32 macaques with a common boosting module comprising five FP/Trimer immunizations. We found that FP priming to imprint cross-reactive FP-directed HIV-neutralizing responses, with FP-trimer cocktail elicited the earliest cross-strain responses.
6. Fusion Peptide Priming Reduces Immune Responses to HIV-1 Envelope Trimer Base. Soluble ‘SOSIP’-stabilized envelope (Env) trimers are promising HIV-vaccine immunogens. However, they induce high titer responses against the glycan-free trimer base, which is occluded on native virions. To delineate the impact on base responses of priming with immunogens targeting the fusion peptide (FP) site of vulnerability, we quantified the prevalence of trimer-base antibody responses in 49 non-human primates (NHPs) immunized with various SOSIP-stabilized Env trimers and FP-carrier conjugates. We found that trimer-base responses accounted for ~90% of the overall trimer response in animals immunized with trimer only, ~70% in animals immunized with a cocktail of SOSIP-trimer and FP-conjugate, and ~30% in animals primed with FP-conjugate prior to trimer immunization, with neutralization breadth in FP-conjugate-primed animals correlated inversely with trimer-base responses.
M.D., Shandong University, China
Ph.D., Saitama Medical University, Japan
Dr. Duan received her M.D. degree from Shandong University, China, and received her Ph.D. degree from Saitama Medical University, Japan in Biomedical Research/Microbiology. She worked as a Postdoctoral Research Fellow in U.S. Food and Drug Administration, (CBER), Laboratory of Hepatitis Viruses between 2008-2014. She joined Vaccine Research Center in 2014.
Dose, Safety, Tolerability, and Immunogenicity of an HIV-1 Vaccine, VRC-HIVRGP096-00-VP, With Alum in Healthy Adults: NCT03783130
- VRC018, BG505 DS SOSIP trial
Kong R, Duan H, Sheng Z, Xu K, Acharya P, Chen X, Cheng C, Dingens AS, Gorman J, Sastry M, Shen CH, Zhang B, Zhou T, Chuang GY, Chao CW, Gu Y, Jafari AJ, Louder MK, O'Dell S, Rowshan AP, Viox EG, Wang Y, Choi CW, Corcoran MM, Corrigan AR, Dandey VP, Eng ET, Geng H, Foulds KE, Guo Y, Kwon YD, Lin B, Liu K, Mason RD, Nason MC, Ohr TY, Ou L, Rawi R, Sarfo EK, Schön A, Todd JP, Wang S, Wei H, Wu W; NISC Comparative Sequencing Program, Mullikin JC, Bailer RT, Doria-Rose NA, Karlsson Hedestam GB, Scorpio DG, Overbaugh J, Bloom JD, Carragher B, Potter CS, Shapiro L, Kwong PD, Mascola JR. Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization. Cell. 2019 Jul 25;178(3):567-584.e19.
Duan H, Chen X, Boyington JC, Cheng C, Zhang Y, Jafari AJ, Stephens T, Tsybovsky Y, Kalyuzhniy O, Zhao P, Menis S, Nason MC, Normandin E, Mukhamedova M, DeKosky BJ, Wells L, Schief WR, Tian M, Alt FW, Kwong PD, Mascola JR. Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies. Immunity. 2018 Aug 21;49(2):301-311.e5.
Tian M, Cheng C, Chen X, Duan H, Cheng HL, Dao M, Sheng Z, Kimble M, Wang L, Lin S, Schmidt SD, Du Z, Joyce MG, Chen Y, DeKosky BJ, Chen Y, Normandin E, Cantor E, Chen RE, Doria-Rose NA, Zhang Y, Shi W, Kong WP, Choe M, Henry AR, Laboune F, Georgiev IS, Huang PY, Jain S, McGuire AT, Georgeson E, Menis S, Douek DC, Schief WR, Stamatatos L, Kwong PD, Shapiro L, Haynes BF, Mascola JR, Alt FW. Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires. Cell. 2016 Sep 8;166(6):1471-1484.e18.
Duan H, Kachko A, Zhong L, Struble E, Pandey S, Yan H, Harman C, Virata-Theimer ML, Deng L, Zhao Z, Major M, Feinstone S, Zhang P. Amino acid residue-specific neutralization and nonneutralization of hepatitis C virus by monoclonal antibodies to the E2 protein. J Virol. 2012 Dec;86(23):12686-94.
Duan H, Takagi A, Kayano H, Koyama I, Morisseau C, Hammock BD, Akatsuka T. Monoclonal antibodies reveal multiple forms of expression of human microsomal epoxide hydrolase. Toxicol Appl Pharmacol. 2012 Apr 1;260(1):27-34.
Duan H, Struble E, Zhong L, Mihalik K, Major M, Zhang P, Feinstone S, Feigelstock D. Hepatitis C virus with a naturally occurring single amino-acid substitution in the E2 envelope protein escapes neutralization by naturally-induced and vaccine-induced antibodies. Vaccine. 2010 Jun 7;28(25):4138-44.
Tools/Resources / Core Facilities
Probes, B cell sorting and primers for mouse, NHP B cell sequencing.