Review
Immunology
Stephen R. Walsh, Michael S. Seaman
Summary: The current clinical studies are actively exploring the use of bnAbs as passive immunization strategies to prevent HIV-1 infection. Recent trials have shown that bnAbs can provide protection against HIV-1 infection in humans, but there are still significant barriers to overcome.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Matthijs Meijers, Kanika Vanshylla, Henning Gruell, Florian Klein, Michael Laessig
Summary: Broadly neutralizing antibodies show promise in treating and preventing HIV-1 infections, but the virus often evolves resistance. A fitness model based on in vivo data accurately predicts the dynamics of HIV-1 escape during antibody treatment, highlighting an evolutionary trade-off between antibody resistance and its collateral cost.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemical Research Methods
Vlad-Rares Danaila, Catalin Buiu
Summary: This article presents a method based on neural networks and transfer learning to predict the sensitivity of HIV antibodies using the CATNAP dataset. Compared to other methods, this approach achieves better predictive performance and does not require structural features, making it more practical.
Review
Immunology
Denise C. C. Hsu, John W. W. Mellors, Sandhya Vasan
Summary: Broadly neutralizing antibodies (bnAbs) targeting the HIV-1 envelope glycoprotein are promising strategies for HIV-1 prevention, treatment, and remission. Research on the combination of bnAbs with different resistance profiles is essential to address concerns about HIV-1 resistance. Additionally, studies on bnAbs in preclinical models and clinical trials are important to optimize therapeutic outcomes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biology
Colin LaMont, Jakub Otwinowski, Kanika Vanshylla, Henning Gruell, Florian Klein, Armita Nourmohammad
Summary: This study proposes a computational approach based on the population genetics of HIV escape to predict the efficacy of bNAb therapy. By using high-throughput HIV sequence data from bNAb-naive patients to parametrize HIV escape, the distribution of rebound times in three clinical trials is predicted. It is shown that a combination of three bNAbs is necessary to effectively suppress viral escape.
Article
Biochemistry & Molecular Biology
Oluwarotimi Omorodion, Ian A. Wilson
Summary: This study investigates the cysteinylation in a lineage of broadly neutralizing antibodies targeting the N332-glycan supersite on the surface envelope glycoprotein (Env) of HIV-1. Through chromatography and mass spectrometry, subpopulations of cysteinylated and noncysteinylated antibodies expressed in mammalian cells were characterized. The crystal structures of two PCDN antibodies represent the first structures of a cysteinylated antibody and show that the cysteinylation in this case is located in CDRH3. Biophysical studies indicate that cysteinylation of these HIV-1 antibodies does not interfere with antigen binding, which differs from other cysteinylated antibodies.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Young-Jun Park, Dora Pinto, Alexandra C. Walls, Zhuoming Liu, Anna De Marco, Fabio Benigni, Fabrizia Zatta, Chiara Silacci-Fregni, Jessica Bassi, Kaitlin R. Sprouse, Amin Addetia, John E. Bowen, Cameron Stewart, Martina Giurdanella, Christian Saliba, Barbara Guarino, Michael A. Schmid, Nicholas M. Franko, Jennifer K. Logue, Ha V. Dang, Kevin Hauser, Julia di Iulio, William Rivera, Gretja Schnell, Anushka Rajesh, Jiayi Zhou, Nisar Farhat, Hannah Kaiser, Martin Montiel-Ruiz, Julia Noack, Florian A. Lempp, Javier Janer, Rana Abdelnabi, Piet Maes, Paolo Ferrari, Alessandro Ceschi, Olivier Giannini, Guilherme Dias De Melo, Lauriane Kergoat, Herve Bourhy, Johan Neyts, Leah Soriaga, Lisa A. Purcell, Gyorgy Snell, Sean P. J. Whelan, Antonio Lanzavecchia, Herbert W. Virgin, Luca Piccoli, Helen Y. Chu, Matteo Samuele Pizzuto, Davide Corti, David Veesler
Summary: SARS-CoV-2 Omicron sublineages have spike mutations that allow them to evade antibodies from previous infection or vaccination. Hybrid immunity or booster shots can generate neutralizing antibodies against Omicron variants, and breakthrough infections lead to the production of neutralizing antibodies in the nasal mucosa. Antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases show cross-reactivity with different receptor-binding domains, while primary Omicron infections elicit B cells with narrow specificity. A highly potent pan-variant-neutralizing antibody has been identified as a potential candidate for clinical development.
Article
Immunology
Simone I. I. Richardson, Frances Ayres, Nelia P. P. Manamela, Brent Oosthuysen, Zanele Makhado, Bronwen E. E. Lambson, Lynn Morris, Penny L. L. Moore
Summary: The study revealed that IgG3 bNAbs demonstrate stronger protective ability and phagocytosis against HIV infection, especially against certain specific HIV strains, indicating that altering the constant region of antibodies may enhance their neutralizing and Fc effector activity.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Virology
Jack M. Edwards, Behnaz Heydarchi, Georges Khoury, Natalia A. Salazar-Quiroz, Christopher A. Gonelli, Bruce Wines, P. Mark Hogarth, Anne B. Kristensen, Matthew S. Parsons, Damian F. J. Purcell
Summary: The study successfully enhanced the Fc-mediated effector functions of the bovine-human chimeric bNAb NC-Cow1 with an ultralong CDRH3, improving neutralization activity and cell potency against HIV-1 while maintaining envelope binding. This research is significant for the development of multifunctional anti-HIV antibodies and enhancing prevention of HIV-1 transmission.
JOURNAL OF VIROLOGY
(2021)
Article
Immunology
Martina S. Wesley, Kelvin T. Chiong, Kelly E. Seaton, Christine A. Arocena, Sheetal Sawant, Jonathan Hare, Kasey Hernandez, Michelle Rojas, Jack Heptinstall, David Beaumont, Katherine Crisafi, Joseph Nkolola, Dan H. Barouch, Marcella Sarzotti-Kelsoe, Georgia D. Tomaras, Nicole L. Yates
Summary: The recent AMP trials demonstrated the potential of blocking infection from sensitive HIV-1 strains through the infusion of specific antibodies. An accurate measurement method for in vivo concentrations of passively infused antibodies was developed to determine effective doses for therapy and/or prevention. Additionally, the study explored the use of triple combinations of antibodies for HIV-1 prevention.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Jessica Hong, Hyung Joon Kwon, Raul Cachau, Catherine Z. Chen, Kevin John Butay, Zhijian Duan, Dan Li, Hua Ren, Tianyuzhou Liang, Jianghai Zhu, Venkata P. Dandey, Negin P. Martin, Dominic Esposito, Uriel Ortega-Rodriguez, Miao Xu, Mario J. Borgnia, Hang Xie, Mitchell Ho
Summary: The study constructed large dromedary camel VHH phage libraries and successfully isolated two high-affinity nanobodies that showed broad neutralization activity against SARS-CoV-2 and its variants. These nanobodies can be used for therapeutic purposes against COVID-19 variants, and the dromedary camel VHH phage libraries serve as a unique platform for rapidly isolating potent nanobodies against future emerging viruses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Virology
Soohyun Kim, Maria V. Filsinger V. Interrante, Peter S. S. Kim
Summary: The trimeric glycoprotein Env on the surface of HIV-1 is the target of broadly neutralizing antibodies and vaccine development efforts. Antibodies that target the membrane proximal external region (MPER) of Env show lipid-binding characteristics and increasing their local concentration through binding to the Fc receptor Fc gamma RI can potentiate their ability to prevent viral entry. This study shows that lipid-binding activity and Fc gamma RI-mediated potentiation work together to improve the potency of MPER-directed antibodies by increasing their local concentration near the site of viral fusion.
JOURNAL OF VIROLOGY
(2023)
Article
Multidisciplinary Sciences
Sai Luo, Changbin Jing, Adam Yongxin Ye, Sven Kratochvil, Christopher A. Cottrell, Ja-Hyun Koo, Aimee Chapdelaine Williams, Lucas Vieira Francisco, Himanshu Batra, Edward Lamperti, Oleksandr Kalyuzhniy, Yuxiang Zhang, Alessandro Barbieri, John P. Manis, Barton F. Haynes, William R. Schief, Facundo D. Batista, Ming Tian, Frederick W. Alt
Summary: Antibody heavy chain and light chain variable region exons are assembled through V(D)J recombination. HIV-1 vaccine strategies aim to induce broadly neutralizing antibodies against HIV-1. Using rearranging mouse models can help better evaluate vaccine effectiveness.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Julie Lucas, Li-Yun Lin, Nicodeme Paul, Geraldine Laumond, Jeromine Klingler, Sylvie Schmidt, Julia Frappier, Asma Essat, Laurence Meyer, Alicia Castro Gordon, Cecile Goujard, Seiamak Bahram, Christiane Moog
Summary: The study found that neutralizing antibodies preferentially directed against early-transmitted founder (T/F) viruses can be induced following HIV infection. These early-induced neutralizing antibodies may have lesser maturation characteristics, making them more interesting for future vaccine designs.
Article
Medicine, General & Internal
Jingxin Li, Li Zhang, Linlin Bao, Yuxiao Wang, Lin Qiu, Jialei Hu, Rong Tang, Huiyan Yu, Jun Shan, Yan Li, Chuan Qin, Fengcai Zhu
Summary: This study isolated specific B cells from patients infected with H7N9 and generated a human monoclonal antibody (mAb) called 6-137. mAb 6-137 can recognize and neutralize the H7N9 virus, providing preventive and therapeutic effects in mouse models.
CHINESE MEDICAL JOURNAL
(2022)
Article
Multidisciplinary Sciences
Lihong Liu, Sho Iketani, Yicheng Guo, Jasper F-W Chan, Maple Wang, Liyuan Liu, Yang Luo, Hin Chu, Yiming Huang, Manoj S. Nair, Jian Yu, Kenn K-H Chik, Terrence T-T Yuen, Chaemin Yoon, Kelvin K-W To, Honglin Chen, Michael T. Yin, Magdalena E. Sobieszczyk, Yaoxing Huang, Harris H. Wang, Zizhang Sheng, Kwok-Yung Yuen, David D. Ho
Summary: The B.1.1.529/Omicron variant of SARS-CoV-2, initially detected in southern Africa, has rapidly spread globally and is expected to become dominant due to its enhanced transmissibility in the coming weeks. This variant poses a threat to the efficacy of current COVID-19 vaccines and antibody therapies due to its significant antibody resistance. Even individuals who have received vaccines and booster doses may have reduced neutralizing activity against B.1.1.529.
Article
Multidisciplinary Sciences
Svenja Weiss, Vincenza Itri, Ruimin Pan, Xunqing Jiang, Christina C. Luo, Lynn Morris, Delphine C. Malherbe, Philip Barnette, Jeff Alexander, Xiang-Peng Kong, Nancy L. Haigwood, Ann J. Hessell, Ralf Duerr, Susan Zolla-Pazner
Summary: The authors demonstrate that an HIV vaccine targeting the V1V2 region of gp120 is superior to whole envelope vaccines or natural infection in inducing V1V2 antibodies with anti-viral functions that correlate with protection.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Gabriele Cerutti, Yicheng Guo, Lihong Liu, Liyuan Liu, Zhening Zhang, Yang Luo, Yiming Huang, Harris H. Wang, David D. Ho, Zizhang Sheng, Lawrence Shapiro
Summary: The Omicron variant of SARS-CoV-2, known for its high ability to evade neutralizing antibodies, has been found to have 34 mutations in the spike protein, with 15 of them occurring in the receptor-binding domain (RBD). A cryo-EM structure of the Omicron spike protein reveals that it is exclusively in the 1-RBD-up conformation, with high mobility of RBD. These mutations in the spike protein cause steric clashes and altered interactions at antibody-binding surfaces, as well as changes in local regions that interfere with antibody recognition.
Article
Immunology
Pengfei Wang, Ryan G. Casner, Manoj S. Nair, Jian Yu, Yicheng Guo, Maple Wang, Jasper F-W Chan, Gabriele Cerutti, Sho Iketani, Lihong Liu, Zizhang Sheng, Zhiwei Chen, Kwok-Yung Yuen, Peter D. Kwong, Yaoxing Huang, Lawrence Shapiro, David D. Ho
Summary: The development of potent and broad-spectrum antiviral therapeutics and vaccines is crucial in dealing with highly pathogenic human coronaviruses and their evolving variants. Monoclonal antibody 2-36, isolated from COVID-19-convalescent patients, has been found to cross-neutralize SARS-CoV and other coronaviruses. The cryo-EM structure of 2-36 with SARS-CoV-2 and SARS-CoV spike reveals a conserved epitope in the receptor-binding domain (RBD). This antibody can neutralize various SARS-CoV-2 variants, as well as bat and pangolin sarbecoviruses that use human ACE2 as a receptor.
EMERGING MICROBES & INFECTIONS
(2022)
Article
Immunology
Zizhang Sheng, Jude S. Bimela, Phinikoula S. Katsamba, Saurabh D. Patel, Yicheng Guo, Haiqing Zhao, Youzhong Guo, Peter D. Kwong, Lawrence Shapiro
Summary: This study used molecular dynamics simulation and data mining to investigate the effects of individual and combination somatic hypermutations (SHMs) on antibody conformation, flexibility, stability, and affinity. The researchers identified a common mechanism of modulation of heavy-light pairing orientation through disruption of a conserved hydrogen-bond network. They also observed remote epistasis between certain SHMs.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Virology
Jieshi Yu, Chen Huang, Zhao Wang, Radhey S. Kaushik, Zizhang Sheng, Feng Li, Dan Wang
Summary: In this study, a method to measure and identify the interaction of ZIKV capsid proteins was developed, and peptides that can inhibit the multimerization of ZIKV capsid were identified. This study is of great importance for the future discovery of ZIKV assembly inhibitors.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Article
Multidisciplinary Sciences
Qian Wang, Yicheng Guo, Sho Iketani, Manoj S. Nair, Zhiteng Li, Hiroshi Mohri, Maple Wang, Jian Yu, Anthony D. Bowen, Jennifer Y. Chang, Jayesh G. Shah, Nadia Nguyen, Zhiwei Chen, Kathrine Meyers, Michael T. Yin, Magdalena E. Sobieszczyk, Zizhang Sheng, Yaoxing Huang, Lihong Liu, David D. Ho
Summary: SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have become dominant in the United States and South Africa, raising concerns about their ability to evade neutralizing antibodies and compromise the efficacy of COVID-19 vaccines and therapeutic monoclonals. A systematic antigenic analysis reveals that BA.2.12.1 and BA.4/5 have different levels of resistance to antibodies, with BA.2.12.1 being modestly resistant and BA.4/5 being substantially resistant. Certain mutations in the spike protein facilitate antibody escape, but compromise the spike affinity for the viral receptor. Only bebtelovimab retains full potency against both subvariants.
Article
Microbiology
Qian Wang, Sho Iketani, Zhiteng Li, Yicheng Guo, Andre Yanchen Yeh, Michael Liu, Jian Yu, Zizhang Sheng, Yaoxing Huang, Lihong Liu, David D. Ho
Summary: The newly emerged SARS-CoV-2 Omicron subvariant BA.2.75 exhibits moderate resistance to neutralization by sera from vaccinated/boosted individuals compared to the currently circulating BA.2, but is more sensitive than BA.4/5. BA.2.75 shows heightened resistance to class 1 and class 3 monoclonal antibodies targeting the spike-receptor-binding domain, while gaining sensitivity to class 2 antibodies. The resistance is mainly conferred by two mutations. BA.2.75 also shows slight resistance to a therapeutic antibody with potent activity against all Omicron subvariants. Additionally, BA.2.75 exhibits higher binding affinity to the host receptor ACE2 compared to other Omicron subvariants.
CELL HOST & MICROBE
(2022)
Letter
Infectious Diseases
Qian Wang, Zhiteng Li, Jerren Ho, Yicheng Guo, Andre Yanchen Yeh, Hiroshi Mohri, Michael Liu, Maple Wang, Jian Yu, Jayesh G. Shah, Jennifer Y. Chang, Favio Herbas, Michael T. Yin, Magdalena E. Sobieszczyk, Zizhang Sheng, Lihong Liu, David Ho
LANCET INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Qian Wang, Sho Lekthan, Zhiten Li, Liyua Liu, Yichen Guo, Yiming Huang, Anthony D. Bowen, Michael Liu, Maple Wang, Jian Yu, Riccardo Valdez, Adam S. Lauring, Zizhang Sheng, Harris H. Wang, Aubree Gordon, Lihong Liu, David D. Ho
Summary: The BQ and XBB subvariants of SARS-CoV-2 Omicron, with additional spike mutations, are rapidly expanding and have altered antibody evasion properties. Neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by vaccinated individuals and infected persons' sera was significantly impaired, including those boosted with a WA1/BA.5 bivalent mRNA vaccine. The titers against BQ and XBB subvariants were much lower than observed before, indicating that these subvariants pose a serious threat to current COVID-19 vaccines and render all authorized antibodies inactive.
Article
Multidisciplinary Sciences
Sho Iketani, Hiroshi Mohri, Bruce Culbertson, Seo Jung Hong, Yinkai Duan, Maria Luck, Medini K. Annavajhala, Yicheng Guo, Zizhang Sheng, Anne-Catrin Uhlemann, Stephen P. Goff, Yosef Sabo, Haitao Yang, Alejandro Chavez, David D. Ho
Summary: Nirmatrelvir, an experimental oral antiviral, has shown clinical usefulness against COVID-19. However, there is concern that SARS-CoV-2 could develop resistance to this drug. In vitro studies have demonstrated that highly resistant viruses can emerge from SARS-CoV-2 when exposed to Nirmatrelvir, with mutations in the 3CL protease. These findings provide insights into the mechanisms of resistance and can inform the development of next-generation protease inhibitors.
Article
Multidisciplinary Sciences
Khadidiatou Mangou, Adam J. Moore, Laty Gaye Thiam, Aboubacar Ba, Alessandra Orfano, Ife Desamours, Duncan Ndungu Ndegwa, Justin Goodwin, Yicheng Guo, Zizhang Sheng, Saurabh D. Patel, Fatoumata Diallo, Seynabou D. Sene, Mariama N. Pouye, Awa Thioub Faye, Alassane Thiam, Vanessa Nunez, Cheikh Tidiane Diagne, Bacary Djilocalisse Sadio, Lawrence Shapiro, Ousmane Faye, Alassane Mbengue, Amy K. Bei
Summary: The lack of progress in reducing global malaria deaths highlights the need for a highly effective vaccine. One major challenge in vaccine development is the diverse nature of Plasmodium falciparum antigens, which has been overlooked in previous evaluations. This study uses genomic approaches to evaluate the genetic diversity of the malaria vaccine candidate PfRh5 and identifies novel single nucleotide polymorphisms (SNPs) in the gene. The findings demonstrate that PfRh5 exhibits greater genetic diversity than previously described, with the potential for functional implications on immune evasion and receptor binding. These findings support continued efforts in validating PfRh5 as an effective malaria vaccine target and developing a PfRh5 vaccine.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Andrew Beenken, Gabriele Cerutti, Julia Brasch, Yicheng Guo, Zizhang Sheng, Hediye Erdjument-Bromage, Zainab Aziz, Shelief Y. Robbins-Juarez, Estefania Y. Chavez, Goran Ahlsen, Phinikoula S. Katsamba, Thomas A. Neubert, Anthony W. P. Fitzpatrick, Jonathan Barasch, Lawrence Shapiro
Summary: In this study, high-resolution cryoelectron microscopy structures of LRP2 were analyzed, revealing that LRP2 is a molecular machine capable of binding ligands at the cell surface and releasing them in the endosome. LRP2 forms a homodimer and its conformational transformation is regulated by pH-sensitive sites. Deleterious missense variants of LRP2 appear to impair homodimer assembly. These observations provide insights into the function and mechanism of LDL receptors and suggest that homodimerization is a conserved feature of the LRP receptor subfamily.
Article
Infectious Diseases
Lihong Liu, Kathrine Meyers, Lawrence J. Purpura, Nadia Nguyen, Hiroshi Mohri, Jennifer Y. Chang, Medini K. Annavajhala, Leo Lopez, Sang Won Lee, Jayesh Shah, Benjamin Lane, Anyelina Cantos, Sade A. Tukuru, Yicheng Guo, Kenra Ford, Yueh-Ting Chiu, Zizhang Sheng, Tenzin Choesang, Delivette Castor, Maple Wang, Christina Pili, Michael N. Van Hoy, Andrew Wallach, Jamie Horton, Zhiqiang Chen, Susan Rosenthal, Son McLaren, Baowei Jiang, Frank Wang, Helen H. Lu, Anne-Catrin Uhlemann, David D. Ho, Michael T. Yin
Summary: The development of a rapid antigen test using two pairs of monoclonal antibodies has resulted in a high-performing test that remains effective across multiple variants in both laboratory and clinical evaluations. The test is capable of identifying almost all individuals carrying infectious SARS-CoV-2.
JOURNAL OF CLINICAL VIROLOGY PLUS
(2022)
Article
Multidisciplinary Sciences
Sho Iketani, Lihong Liu, Yicheng Guo, Liyuan Liu, Jasper F-W Chan, Yiming Huang, Maple Wang, Yang Luo, Jian Yu, Hin Chu, Kenn K-H Chik, Terrence T-T Yuent, Michael T. Yin, Magdalena E. Sobieszczyk, Yaoxing Huang, Kwok-Yung Yuen, Harris H. Wang, Zizhang Sheng, David D. Ho
Summary: The identification of the Omicron variant of SARS-CoV-2 in Botswana in November 2021 sparked concern due to the spike protein alterations that could potentially evade antibodies. Further studies showed that the Omicron sublineages, BA.1+R346K and BA.2, are antigenically similar to the wild-type virus and pose similar risks to the effectiveness of current vaccines. BA.2 also demonstrated resistance to many neutralizing monoclonal antibodies, highlighting the challenges in developing effective therapeutic options.