Search

Your search keyword '"Schiffner, Torben"' showing total 49 results
Start Over Author "Schiffner, Torben"
49 results on '"Schiffner, Torben"'

1. Vaccination induces broadly neutralizing antibody precursors to HIV gp41

Author

Schiffner, Torben, Phung, Ivy, Ray, Rashmi, Irimia, Adriana, Tian, Ming, Swanson, Olivia, Lee, Jeong Hyun, Lee, Chang-Chun D., Marina-Zárate, Ester, Cho, So Yeon, Huang, Jiachen, Ozorowski, Gabriel, Skog, Patrick D., Serra, Andreia M., Rantalainen, Kimmo, Allen, Joel D., Baboo, Sabyasachi, Rodriguez, Oscar L., Himansu, Sunny, Zhou, Jianfu, Hurtado, Jonathan, Flynn, Claudia T., McKenney, Katherine, Havenar-Daughton, Colin, Saha, Swati, Shields, Kaitlyn, Schultze, Steven, Smith, Melissa L., Liang, Chi-Hui, Toy, Laura, Pecetta, Simone, Lin, Ying-Cing, Willis, Jordan R., Sesterhenn, Fabian, Kulp, Daniel W., Hu, Xiaozhen, Cottrell, Christopher A., Zhou, Xiaoya, Ruiz, Jennifer, Wang, Xuesong, Nair, Usha, Kirsch, Kathrin H., Cheng, Hwei-Ling, Davis, Jillian, Kalyuzhniy, Oleksandr, Liguori, Alessia, Diedrich, Jolene K., Ngo, Julia T., Lewis, Vanessa, Phelps, Nicole, Tingle, Ryan D., Spencer, Skye, Georgeson, Erik, Adachi, Yumiko, Kubitz, Michael, Eskandarzadeh, Saman, Elsliger, Marc A., Amara, Rama R., Landais, Elise, Briney, Bryan, Burton, Dennis R., Carnathan, Diane G., Silvestri, Guido, Watson, Corey T., Yates, III, John R., Paulson, James C., Crispin, Max, Grigoryan, Gevorg, Ward, Andrew B., Sok, Devin, Alt, Frederick W., Wilson, Ian A., Batista, Facundo D., Crotty, Shane, and Schief, William R.

Published
2024
Full Text
View/download PDF

2. Affinity gaps among B cells in germinal centers drive the selection of MPER precursors

Author

Ray, Rashmi, Schiffner, Torben, Wang, Xuesong, Yan, Yu, Rantalainen, Kimmo, Lee, Chang-Chun David, Parikh, Shivang, Reyes, Raphael A., Dale, Gordon A., Lin, Ying-Cing, Pecetta, Simone, Giguere, Sophie, Swanson, Olivia, Kratochvil, Sven, Melzi, Eleonora, Phung, Ivy, Madungwe, Lisa, Kalyuzhniy, Oleksandr, Warner, John, Weldon, Stephanie R., Tingle, Ryan, Lamperti, Edward, Kirsch, Kathrin H., Phelps, Nicole, Georgeson, Erik, Adachi, Yumiko, Kubitz, Michael, Nair, Usha, Crotty, Shane, Wilson, Ian A., Schief, William R., and Batista, Facundo D.

Published
2024
Full Text
View/download PDF

3. Author Correction: Vaccination induces broadly neutralizing antibody precursors to HIV gp41

Author

Schiffner, Torben, Phung, Ivy, Ray, Rashmi, Irimia, Adriana, Tian, Ming, Swanson, Olivia, Lee, Jeong Hyun, Lee, Chang-Chun D., Marina-Zárate, Ester, Cho, So Yeon, Huang, Jiachen, Ozorowski, Gabriel, Skog, Patrick D., Serra, Andreia M., Rantalainen, Kimmo, Allen, Joel D., Baboo, Sabyasachi, Rodriguez, Oscar L., Himansu, Sunny, Zhou, Jianfu, Hurtado, Jonathan, Flynn, Claudia T., McKenney, Katherine, Havenar-Daughton, Colin, Saha, Swati, Shields, Kaitlyn, Schultze, Steven, Smith, Melissa L., Liang, Chi-Hui, Toy, Laura, Pecetta, Simone, Lin, Ying-Cing, Willis, Jordan R., Sesterhenn, Fabian, Kulp, Daniel W., Hu, Xiaozhen, Cottrell, Christopher A., Zhou, Xiaoya, Ruiz, Jennifer, Wang, Xuesong, Nair, Usha, Kirsch, Kathrin H., Cheng, Hwei-Ling, Davis, Jillian, Kalyuzhniy, Oleksandr, Liguori, Alessia, Diedrich, Jolene K., Ngo, Julia T., Lewis, Vanessa, Phelps, Nicole, Tingle, Ryan D., Spencer, Skye, Georgeson, Erik, Adachi, Yumiko, Kubitz, Michael, Eskandarzadeh, Saman, Elsliger, Marc A., Amara, Rama R., Landais, Elise, Briney, Bryan, Burton, Dennis R., Carnathan, Diane G., Silvestri, Guido, Watson, Corey T., Yates, III, John R., Paulson, James C., Crispin, Max, Grigoryan, Gevorg, Ward, Andrew B., Sok, Devin, Alt, Frederick W., Wilson, Ian A., Batista, Facundo D., Crotty, Shane, and Schief, William R.

Published
2024
Full Text
View/download PDF

4. Profound structural conservation of chemically cross-linked HIV-1 envelope glycoprotein experimental vaccine antigens

Author

Martin, Gregory M., Russell, Rebecca A., Mundsperger, Philip, Harris, Scarlett, Jovanoska, Lu, Trajano, Luiza Farache, Schiffner, Torben, Fabian, Katalin, Tolazzi, Monica, Scarlatti, Gabriella, McFarlane, Leon, Cheeseman, Hannah, Aldon, Yoann, Schermer, Edith E., Breemen, Marielle, Sliepen, Kwinten, Katinger, Dietmar, Kunert, Renate, Sanders, Rogier W., Shattock, Robin, Ward, Andrew B., and Sattentau, Quentin J.

Published
2023
Full Text
View/download PDF

7. Heterologous prime-boost vaccination drives early maturation of HIV broadly neutralizing antibody precursors in humanized mice.

Author

Cottrell, Christopher A., Hu, Xiaozhen, Lee, Jeong Hyun, Skog, Patrick, Luo, Sai, Flynn, Claudia T., McKenney, Katherine R., Hurtado, Jonathan, Kalyuzhniy, Oleksandr, Liguori, Alessia, Willis, Jordan R., Landais, Elise, Raemisch, Sebastian, Chen, Xuejun, Baboo, Sabyasachi, Himansu, Sunny, Diedrich, Jolene K., Duan, Hongying, Cheng, Cheng, and Schiffner, Torben

Subjects
BOOSTER vaccines, VACCINATION, VACCINE effectiveness, HIV infections, IMMUNOGLOBULINS
Abstract

A protective HIV vaccine will likely need to induce broadly neutralizing antibodies (bnAbs). Vaccination with the germline-targeting immunogen eOD-GT8 60mer adjuvanted with AS01B was found to induce VRC01-class bnAb precursors in 97% of vaccine recipients in the IAVI G001 phase 1 clinical trial; however, heterologous boost immunizations with antigens more similar to the native glycoprotein will be required to induce bnAbs. Therefore, we designed core-g28v2 60mer, a nanoparticle immunogen to be used as a first boost after eOD-GT8 60mer priming. We found, using a humanized mouse model approximating human conditions of VRC01-class precursor B cell diversity, affinity, and frequency, that both protein- and mRNA-based heterologous prime-boost regimens induced VRC01-class antibodies that gained key mutations and bound to near-native HIV envelope trimers lacking the N276 glycan. We further showed that VRC01-class antibodies induced by mRNA-based regimens could neutralize pseudoviruses lacking the N276 glycan. These results demonstrated that heterologous boosting can drive maturation toward VRC01-class bnAb development and supported the initiation of the IAVI G002 phase 1 trial testing mRNA-encoded nanoparticle prime-boost regimens. Editor's summary: For a vaccine regimen to be effective against HIV infection, it will need to elicit broadly neutralizing antibodies (bnAbs). However, strategies to elicit bnAbs in humans with a vaccine have not been successful to date. A different strategy, germline-targeting vaccine design, relies on a priming immunogen to first induce bnAb precursors and then a series of heterologous boosters to drive the maturation of bnAb precursors to produce bnAbs. The first step in this process, elicitation of bnAb precursors, has proven successful in clinical trials. Here, Cottrell et al. take the next step by designing and testing the first booster immunogen in the shepherding process. Vaccination of eOD-GT8 60mer-primed humanized mice with their immunogen, core-g28v2 60mer, in either protein or mRNA form resulted in antibodies that were closer to bnAbs than those that received a placebo booster. These data support the ongoing clinical trial testing core-g28v2 60mer mRNA as a booster vaccine. —Courtney Malo [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

8. B cells expressing authentic naive human VRC01-class BCRs can be recruited to germinal centers and affinity mature in multiple independent mouse models

Author

Huang, Deli, Abbott, Robert K., Havenar-Daughton, Colin, Skog, Patrick D., Al-Kolla, Rita, Groschel, Bettina, Blane, Tanya R., Menis, Sergey, Tran, Jenny Tuyet, Thinnes, Theresa C., Volpi, Sabrina A., Liguori, Alessia, Schiffner, Torben, Villegas, Sophia M., Kalyuzhniy, Oleksandr, Pintea, Mark, Voss, James E., Phelps, Nicole, Tingle, Ryan, Rodriguez, Alberto R., Martin, Greg, Kupryianov, Sergey, deCamp, Allan, Schief, William R., Nemazee, David, and Crotty, Shane

Published
2020

10. Diverse competitor B cell responses to a germline-targeting priming immunogen in human Ig loci transgenic mice

Author

Schiffner, Torben, primary, Palser, Anne, additional, Jardine, Joseph G., additional, Liguori, Alessia, additional, Menis, Sergey, additional, Raemisch, Sebastian, additional, Hu, Xiaozhen, additional, Kulp, Daniel W., additional, Wang, Xiaoning, additional, Diedrich, Jolene K., additional, Groschel, Bettina, additional, Kalyuzhniy, Oleksandr, additional, Tingle, Ryan, additional, Le, Khoa, additional, Georgeson, Erik, additional, Adachi, Yumiko, additional, Kubitz, Michael, additional, Landais, Elise, additional, Yates, John R., additional, Paulson, James C., additional, Sok, Devin, additional, Kellam, Paul, additional, and Schief, William R., additional

Published
2024
Full Text
View/download PDF

12. Correction: HIV-1-neutralizing antibody induced by simian adenovirus- and poxvirus MVA-vectored BG505 native-like envelope trimers

Author

Capucci, Silvia, primary, Wee, Edmund G., additional, Schiffner, Torben, additional, LaBranche, Celia C., additional, Borthwick, Nicola, additional, Cupo, Albert, additional, Dodd, Jonathan, additional, Dean, Hansi, additional, Sattentau, Quentin, additional, Montefiori, David, additional, Klasse, Per J., additional, Sanders, Rogier W., additional, Moore, John P., additional, and Hanke, Tomáš, additional

Published
2023
Full Text
View/download PDF

13. Refocusing antibody responses by chemical modification of vaccine antigens

Author

Schiffner, Torben and Sattentau, Quentin J.

Subjects
616.07, Glycobiology, Biochemistry, Biology, Medical sciences, Biology (medical sciences), Disease prevention, Immunology, Infectious diseases, Pathology, Vaccinology, Viruses, Vaccine Design, Antigenicity, Immunogenicity, Envelope Glycoproteins, Neutralizing Antibody, Glycosylation, Protein Modifications, Glycoconjugates, Chemical Cross-linking
Abstract

The envelope glycoprotein (Env) of Human Immunodeficiency Virus 1 (HIV-1) has developed several immune-evasion mechanisms to avoid the induction of neutralising antibodies, including immunodominant non-neutralising epitopes, conformational flexibility of conserved epitopes, and spontaneous subunit dissociation, thus impeding vaccine development. Here, chemical modification of Env-based vaccine antigens is explored to overcome these obstacles. Firstly, covalent fixation of Env by chemical cross-linking was used to stabilise the conformationally flexible structure and prevent subunit dissociation. Cross-linked Env constructs showed reduced binding of many non-neutralising antibodies whilst largely maintaining antibody recognition by broadly neutralising antibodies. Compared to unmodified material, immunisation with some of these cross-linked proteins led to the induction of significantly increased antibody titres targeting the conserved CD4 binding site of Env despite similar overall antibody titres. These refocused antibody responses resulted in increased serum neutralising titres compared to animals receiving unmodified protein. Secondly, an epitope masking strategy was developed to reduce or eliminate the immunogenicity of neutralisation-irrelevant surfaces. This was achieved using site-selective addition of theoretically immunosilent glycoconjugates to lysine residues. Masking of model protein hen egg lysozyme (HEL) led to site-selective loss of antibody binding to the modification sites in vitro, which translated into refocusing of antibody responses from masked to unmasked epitopes in vivo. Mutant HIV-1 and influenza virus surface glycoproteins were designed that had lysine residues removed from close proximity to the respective broadly neutralising epitopes, but added throughout the remaining surface. Masking of these mutant proteins with second-generation glycoconjugates led to predictable perturbations of antibody binding in vitro. However, administration of these modified glycoproteins revealed unexpectedly that the masking glycans were highly immunogenic in vivo. Thus, this strategy may well prove useful if truly non-immunogenic glycoconjugates can be identified. Taken together, these chemical modifications of vaccine antigens may allow focused targeting of specific antigenic regions for increased B cell recognition, and may thus be a valuable tool for vaccine antigen design.

Published
2014

14. Author Correction: Vaccine elicitation of HIV broadly neutralizing antibodies from engineered B cells

Author

Huang, Deli, Tran, Jenny Tuyet, Olson, Alex, Vollbrecht, Thomas, Tenuta, Mary, Guryleva, Mariia V., Fuller, Roberta P., Schiffner, Torben, Abadejos, Justin R., Couvrette, Lauren, Blane, Tanya R., Saye, Karen, Li, Wenjuan, Landais, Elise, Gonzalez-Martin, Alicia, Schief, William, Murrell, Ben, Burton, Dennis R., Nemazee, David, and Voss, James E.

Published
2020
Full Text
View/download PDF

15. Targeting HIV Env immunogens to B cell follicles in nonhuman primates through immune complex or protein nanoparticle formulations

Author

Martin, Jacob T., Cottrell, Christopher A., Antanasijevic, Aleksandar, Carnathan, Diane G., Cossette, Benjamin J., Enemuo, Chiamaka A., Gebru, Etse H., Choe, Yury, Viviano, Federico, Fischinger, Stephanie, Tokatlian, Talar, Cirelli, Kimberly M., Ueda, George, Copps, Jeffrey, Schiffner, Torben, Menis, Sergey, Alter, Galit, Schief, William R., Crotty, Shane, King, Neil P., Baker, David, Silvestri, Guido, Ward, Andrew B., and Irvine, Darrell J.

Published
2020
Full Text
View/download PDF

17. Vaccination induces HIV broadly neutralizing antibody precursors in humans

Author

Leggat, David J., primary, Cohen, Kristen W., additional, Willis, Jordan R., additional, Fulp, William J., additional, deCamp, Allan C., additional, Kalyuzhniy, Oleksandr, additional, Cottrell, Christopher A., additional, Menis, Sergey, additional, Finak, Greg, additional, Ballweber-Fleming, Lamar, additional, Srikanth, Abhinaya, additional, Plyler, Jason R., additional, Schiffner, Torben, additional, Liguori, Alessia, additional, Rahaman, Farhad, additional, Lombardo, Angela, additional, Philiponis, Vincent, additional, Whaley, Rachael E., additional, Seese, Aaron, additional, Brand, Joshua, additional, Ruppel, Alexis M., additional, Hoyland, Wesley, additional, Yates, Nicole L., additional, Williams, LaTonya D., additional, Greene, Kelli, additional, Gao, Hongmei, additional, Mahoney, Celia R., additional, Corcoran, Martin M., additional, Cagigi, Alberto, additional, Taylor, Alison, additional, Brown, David M., additional, Ambrozak, David R., additional, Sincomb, Troy, additional, Hu, Xiaozhen, additional, Tingle, Ryan, additional, Georgeson, Erik, additional, Eskandarzadeh, Saman, additional, Alavi, Nushin, additional, Lu, Danny, additional, Mullen, Tina-Marie, additional, Kubitz, Michael, additional, Groschel, Bettina, additional, Maenza, Janine, additional, Kolokythas, Orpheus, additional, Khati, Nadia, additional, Bethony, Jeffrey, additional, Crotty, Shane, additional, Roederer, Mario, additional, Karlsson Hedestam, Gunilla B., additional, Tomaras, Georgia D., additional, Montefiori, David, additional, Diemert, David, additional, Koup, Richard A., additional, Laufer, Dagna S., additional, McElrath, M. Juliana, additional, McDermott, Adrian B., additional, and Schief, William R., additional

Published
2022
Full Text
View/download PDF

18. Human immunoglobulin repertoire analysis guides design of vaccine priming immunogens targeting HIV V2-apex broadly neutralizing antibody precursors

Author

Willis, Jordan R., primary, Berndsen, Zachary T., additional, Ma, Krystal M., additional, Steichen, Jon M., additional, Schiffner, Torben, additional, Landais, Elise, additional, Liguori, Alessia, additional, Kalyuzhniy, Oleksandr, additional, Allen, Joel D., additional, Baboo, Sabyasachi, additional, Omorodion, Oluwarotimi, additional, Diedrich, Jolene K., additional, Hu, Xiaozhen, additional, Georgeson, Erik, additional, Phelps, Nicole, additional, Eskandarzadeh, Saman, additional, Groschel, Bettina, additional, Kubitz, Michael, additional, Adachi, Yumiko, additional, Mullin, Tina-Marie, additional, Alavi, Nushin B., additional, Falcone, Samantha, additional, Himansu, Sunny, additional, Carfi, Andrea, additional, Wilson, Ian A., additional, Yates, John R., additional, Paulson, James C., additional, Crispin, Max, additional, Ward, Andrew B., additional, and Schief, William R., additional

Published
2022
Full Text
View/download PDF

19. Immunogenicity of a germline-targeting nanoparticle in knock-in mice expressing human B cell receptors of the HIV gp41 neutralizing antibody, DH511

Author

Cain, Derek Wilson, primary, Tian, Ming, additional, Schiffner, Torben, additional, Rantalainen, Kimmo, additional, Saunders, Kevin O., additional, Wiehe, Kevin, additional, Watts, Brian, additional, Ward, Andrew, additional, Ofek, Gilad, additional, Alt, Frederick W, additional, Haynes, Barton F, additional, Schief, William R, additional, and Alam, S. Munir, additional

Published
2022
Full Text
View/download PDF

20. DeGlyPHER: An Ultrasensitive Method for the Analysis of Viral Spike N-Glycoforms

Author

Baboo, Sabyasachi, Diedrich, Jolene K., Martínez-Bartolomé, Salvador, Wang, Xiaoning, Schiffner, Torben, Groschel, Bettina, Schief, William R., Paulson, James C., and Yates, John R.

Abstract

This is the accepted manuscript version of the work published in its final form as Baboo, S., Diedrich, J. K., Martínez-Bartolomé, S., Wang, X., Schiffner, T., Groschel, B., Schief, W. R., Paulson, J. C., & Yates, J. R. (2021). DeGlyPHER: An Ultrasensitive Method for the Analysis of Viral Spike N-Glycoforms. Analytical Chemistry, 93(40), 13651-13657. https://doi.org/10.1021/acs.analchem.1c03059. Deposited by shareyourpaper.org and openaccessbutton.org. We've taken reasonable steps to ensure this content doesn't violate copyright. However, if you think it does you can request a takedown by emailing help@openaccessbutton.org.

Published
2021
Full Text
View/download PDF

22. Profound structural conservation of chemically cross-linked HIV-1 envelope glycoprotein experimental vaccine antigens

Author

Martin, Gregory, primary, Russell, Rebecca A, additional, Mundsperger, Philip, additional, Harris, Scarlett, additional, Jovanoska, Lu, additional, Trajano, Luiza Farache, additional, Schiffner, Torben, additional, Fabian, Katalin, additional, Tolazzi, Monica, additional, Scarlatti, Gabriella, additional, McFarlane, Leon, additional, Cheeseman, Hannah, additional, Aldon, Yoann, additional, Breemen, Marielle, additional, Sliepen, Kwinten, additional, Katinger, Dietmar, additional, Kunert, Renate, additional, Sanders, Rogier W, additional, Shattock, Robin, additional, Ward, Andrew B, additional, and Sattentau, Quentin J, additional

Published
2021
Full Text
View/download PDF

24. HIV-1 Envelope and MPER Antibody Structures in Lipid Assemblies

Author

Rantalainen, Kimmo, primary, Berndsen, Zachary T., additional, Antanasijevic, Aleksandar, additional, Schiffner, Torben, additional, Zhang, Xi, additional, Lee, Wen-Hsin, additional, Torres, Jonathan L., additional, Zhang, Lei, additional, Irimia, Adriana, additional, Copps, Jeffrey, additional, Zhou, Kenneth H., additional, Kwon, Young D., additional, Law, William H., additional, Schramm, Chaim A., additional, Verardi, Raffaello, additional, Krebs, Shelly J., additional, Kwong, Peter D., additional, Doria-Rose, Nicole A., additional, Wilson, Ian A., additional, Zwick, Michael B., additional, Yates, John R., additional, Schief, William R., additional, and Ward, Andrew B., additional

Published
2020
Full Text
View/download PDF

25. Vaccine Elicitation of HIV Broadly Neutralizing Antibodies from Engineered B cells

Author

Huang, Deli, primary, Tran, Jenny Tuyet, additional, Olson, Alex, additional, Vollbrecht, Thomas, additional, Guryleva, Mariia V., additional, Tenuta, Mary, additional, Fuller, Roberta P., additional, Schiffner, Torben, additional, Abadejos, Justin R., additional, Couvrette, Lauren, additional, Blane, Tanya R., additional, Saye, Karen, additional, Li, Wenjuan, additional, Landais, Elise, additional, Gonzalez-Martin, Alicia, additional, Schief, William, additional, Murrell, Ben, additional, Burton, Dennis R., additional, Nemazee, David, additional, and Voss, James E., additional

Published
2020
Full Text
View/download PDF

26. Targeting HIV Env immunogens to B cell follicles in non-human primates through immune complex or protein nanoparticle formulations

Author

Martin, Jacob T., primary, Cottrell, Christopher A., additional, Antanasijevic, Aleksandar, additional, Carnathan, Diane G., additional, Cossette, Benjamin J., additional, Enemuo, Chiamaka A., additional, Gebru, Etse H., additional, Choe, Yury, additional, Viviano, Federico, additional, Tokatlian, Talar, additional, Cirelli, Kimberly M., additional, Ueda, George, additional, Copps, Jeffrey, additional, Schiffner, Torben, additional, Menis, Sergey, additional, Schief, William R., additional, Crotty, Shane, additional, King, Neil P., additional, Baker, David, additional, Silvestri, Guido, additional, Ward, Andrew B., additional, and Irvine, Darrell J., additional

Published
2020
Full Text
View/download PDF

27. HIV-1 Envelope and MPER antibody structures in lipid assemblies

Author

Rantalainen, Kimmo, primary, Berndsen, Zachary T., additional, Antanasijevic, Aleksandar, additional, Schiffner, Torben, additional, Zhang, Xi, additional, Lee, Wen-Hsin, additional, Torres, Jonathan L., additional, Zhang, Lei, additional, Irimia, Adriana, additional, Copps, Jeffrey, additional, Zhou, Kenneth, additional, Kwon, Young Do, additional, Law, William H., additional, Schramm, Chaim A., additional, Verardi, Raffaello, additional, Krebs, Shelly, additional, Kwong, Peter D., additional, Doria-Rose, Nicole A., additional, Wilson, Ian A., additional, Zwick, Michael B., additional, Yates, John R., additional, Schief, William R., additional, and Ward, Andrew B., additional

Published
2019
Full Text
View/download PDF

28. HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies

Author

Steichen, Jon M., Kulp, Daniel W., Escolano, Amelia, Dosenovic, Pia, Stanfield, Robyn L., McCoy, Laura E., Ozorowski, Gabriel, Hu, Xiaozhen, Kalyuzhniy, Oleksandr, Briney, Bryan, Schiffner, Torben, Garces, Fernando, Freund, Natalia T., Gitlin, Alexander D., Menis, Sergey, Georgeson, Erik, Kubitz, Michael, Adachi, Yumiko, Jones, Meaghan, Mayer, Christian T., Ward, Andrew B., Burton, Dennis R., Wilson, Ian A., Irvine, Darrell J., Nussenzweig, Michel C., Schief, William R., Tokatlian, Talar, Mutafyan, Andrew Ayk, Yun, Dong Soo, Koch Institute for Integrative Cancer Research at MIT, Tokatlian, Talar, Mutafyan, Andrew Ayk, and Yun, Dong Soo

Subjects
Infectious Diseases, Immunology, Immunology and Allergy
Abstract

Broadly neutralizing antibodies (bnAbs) against the N332 supersite of the HIV envelope (Env) trimer are the most common bnAbs induced during infection, making them promising leads for vaccine design. Wild-type Env glycoproteins lack detectable affinity for supersite-bnAb germline precursors and are therefore unsuitable immunogens to prime supersite-bnAb responses. We employed mammalian cell surface display to design stabilized Env trimers with affinity for germline-reverted precursors of PGT121-class supersite bnAbs. The trimers maintained native-like antigenicity and structure, activated PGT121 inferred-germline B cells ex vivo when multimerized on liposomes, and primed PGT121-like responses in PGT121 inferred-germline knockin mice. Design intermediates have levels of epitope modification between wild-type and germline-targeting trimers; their mutation gradient suggests sequential immunization to induce bnAbs, in which the germline-targeting prime is followed by progressively less-mutated design intermediates and, lastly, with native trimers. The vaccine design strategies described could be utilized to target other epitopes on HIV or other pathogens., National Institute of Allergy and Infectious Diseases (U.S.)(CHAVI-ID 1UM1AI1006), National Institute of Allergy and Infectious Diseases (U.S.)(P01 AI110657), National Institute of Allergy and Infectious Diseases (U.S.)(R01 AI08481)

Published
2016
Full Text
View/download PDF

29. Rapid and Focused Maturation of a VRC01-Class HIV Broadly Neutralizing Antibody Lineage Involves Both Binding and Accommodation of the N276-Glycan

Author

Umotoy, Jeffrey, primary, Bagaya, Bernard S., additional, Joyce, Collin, additional, Schiffner, Torben, additional, Menis, Sergey, additional, Saye-Francisco, Karen L., additional, Biddle, Trevor, additional, Mohan, Sanjay, additional, Vollbrecht, Thomas, additional, Kalyuzhniy, Oleksander, additional, Madzorera, Sharon, additional, Kitchin, Dale, additional, Lambson, Bronwen, additional, Nonyane, Molati, additional, Kilembe, William, additional, Poignard, Pascal, additional, Schief, William R., additional, Burton, Dennis R., additional, Murrell, Ben, additional, Moore, Penny L., additional, Briney, Bryan, additional, Sok, Devin, additional, and Landais, Elise, additional

Published
2019
Full Text
View/download PDF

30. HIV-1-neutralizing antibody induced by simian adenovirus- and poxvirus MVA-vectored BG505 native-like envelope trimers

Author

Capucci, Silvia, Wee, Edmund G., Schiffner, Torben, LaBranche, Celia C., Borthwick, Nicola, Cupo, Albert, Dodd, Jonathan, Dean, Hansi, Sattentau, Quentin, Montefiori, David, Klasse, Per J., Sanders, Rogier W., Moore, John P., Hanke, Tomáš, AII - Infectious diseases, Medical Microbiology and Infection Prevention, and Amsterdam institute for Infection and Immunity

Subjects
RNA viruses, Adenoviruses, Physiology, viruses, Disease Vectors, HIV Antibodies, Pathology and Laboratory Medicine, Biochemistry, Immunodeficiency Viruses, Immune Physiology, Medicine and Health Sciences, Vaccines, DNA, Enzyme-Linked Immunoassays, Mammals, AIDS Vaccines, Vaccines, Immune System Proteins, Vaccination, env Gene Products, Human Immunodeficiency Virus, Animal Models, Infectious Diseases, Experimental Organism Systems, Medical Microbiology, Viral Pathogens, Vertebrates, Viruses, Medicine, Rabbits, Pathogens, Viral Vectors, Research Article, Infectious Disease Control, Science, Immunology, Vaccinia virus, Research and Analysis Methods, Microbiology, Antibodies, Cell Line, Virology, Retroviruses, Animals, Humans, Antigens, Immunoassays, Microbial Pathogens, Lentivirus, Organisms, Biology and Life Sciences, Proteins, HIV, Viral Vaccines, Antibodies, Neutralizing, Species Interactions, HEK293 Cells, Amniotes, Immunologic Techniques, HIV-1, Adenoviruses, Simian, Protein Multimerization, DNA viruses, Viral Transmission and Infection
Abstract

Rabbits and monkeys immunized with HIV type 1 (HIV-1) native-like BG505 SOSIP.664 (BG505s) glycoprotein trimers are known to induce antibodies that can neutralize the autologous tier-2 virus. Here, we assessed the induction of HIV-1 trimer binding and neutralizing antibody (nAb) titres when BG505s trimers were also delivered by non-replicating simian (chimpanzee) adenovirus and non-replicating poxvirus modified vaccinia virus Ankara (MVA) vaccine vectors. First, we showed that approximately two-thirds and one-third of the trimers secreted from the ChAdOx1.BG505s (C) and MVA.BG505s (M) vaccine-infected cells, respectively, were cleaved and in a native-like conformation. Rabbits were immunized intramuscularly with these vaccine vectors and in some cases boosted with ISCOMATRIX™-adjuvanted BG505s protein trimer (P), using CCC, MMM, PPP, CPP, MPP and CMP vaccine regimens. We found that the peak trimer-binding antibody and tier-1A and autologous tier-2 nAb responses induced by the CC, CM, PPP, CPP, MPP and CMP regimens were comparable, although only PPP induced autologous tier-2 nAbs in all the immunized animals. Three animals developed weak heterologous tier-2 nAbs. These results demonstrate that ChAdOx1 and MVA vectors are useful delivery modalities for not only T-cell, but also antibody vaccine development.

Published
2017

31. The human naive B cell repertoire contains distinct subclasses for a germline-targeting HIV-1 vaccine immunogen

Author

Havenar-Daughton, Colin, primary, Sarkar, Anita, additional, Kulp, Daniel W., additional, Toy, Laura, additional, Hu, Xiaozhen, additional, Deresa, Isaiah, additional, Kalyuzhniy, Oleksandr, additional, Kaushik, Kirti, additional, Upadhyay, Amit A., additional, Menis, Sergey, additional, Landais, Elise, additional, Cao, Liwei, additional, Diedrich, Jolene K., additional, Kumar, Sonu, additional, Schiffner, Torben, additional, Reiss, Samantha M., additional, Seumois, Grégory, additional, Yates, John R., additional, Paulson, James C., additional, Bosinger, Steven E., additional, Wilson, Ian A., additional, Schief, William R., additional, and Crotty, Shane, additional

Published
2018
Full Text
View/download PDF

32. Structural and immunologic correlates of chemically stabilized HIV-1 envelope glycoproteins

Author

Schiffner, Torben, primary, Pallesen, Jesper, additional, Russell, Rebecca A., additional, Dodd, Jonathan, additional, de Val, Natalia, additional, LaBranche, Celia C., additional, Montefiori, David, additional, Tomaras, Georgia D., additional, Shen, Xiaoying, additional, Harris, Scarlett L., additional, Moghaddam, Amin E., additional, Kalyuzhniy, Oleksandr, additional, Sanders, Rogier W., additional, McCoy, Laura E., additional, Moore, John P., additional, Ward, Andrew B., additional, and Sattentau, Quentin J., additional

Published
2018
Full Text
View/download PDF

33. Rapid and Focused Maturation of a VRC01-Class Broadly Neutralizing Antibody Lineage Involves Both Binding and Accommodation of the N276-Glycan

Author

Umotoy, Jeffrey, primary, Bagaya, Bernard, additional, Joyce, Collin, additional, Menis, Sergey, additional, Schiffner, Torben, additional, Mohan, Sanjay, additional, Vollbrecht, Thomas, additional, Kalyuzhniy, Oleksander, additional, Madzorera, Sharon, additional, Kitchin, Dale, additional, Lambson, Bronwen, additional, Nonyane, Molati, additional, Kilembe, William, additional, Investigators, The IAVI Protocol C, additional, Network, The IAVI African HIV Research, additional, Poignard, Pascal, additional, Schief, William R., additional, Burton, Dennis R., additional, Murrell, Ben, additional, Moore, Penny L., additional, Briney, Bryan, additional, Sok, Devin, additional, and Landais, Elise, additional

Published
2018
Full Text
View/download PDF

34. Structure-based design of native-like HIV-1 envelope trimers to silence non-neutralizing epitopes and eliminate CD4 binding

Author

Kulp, Daniel W., primary, Steichen, Jon M., additional, Pauthner, Matthias, additional, Hu, Xiaozhen, additional, Schiffner, Torben, additional, Liguori, Alessia, additional, Cottrell, Christopher A., additional, Havenar-Daughton, Colin, additional, Ozorowski, Gabriel, additional, Georgeson, Erik, additional, Kalyuzhniy, Oleksandr, additional, Willis, Jordan R., additional, Kubitz, Michael, additional, Adachi, Yumiko, additional, Reiss, Samantha M., additional, Shin, Mia, additional, de Val, Natalia, additional, Ward, Andrew B., additional, Crotty, Shane, additional, Burton, Dennis R., additional, and Schief, William R., additional

Published
2017
Full Text
View/download PDF

35. Lipid interactions and angle of approach to the HIV-1 viral membrane of broadly neutralizing antibody 10E8: Insights for vaccine and therapeutic design

Author

Irimia, Adriana, primary, Serra, Andreia M., additional, Sarkar, Anita, additional, Jacak, Ronald, additional, Kalyuzhniy, Oleksandr, additional, Sok, Devin, additional, Saye-Francisco, Karen L., additional, Schiffner, Torben, additional, Tingle, Ryan, additional, Kubitz, Michael, additional, Adachi, Yumiko, additional, Stanfield, Robyn L., additional, Deller, Marc C., additional, Burton, Dennis R., additional, Schief, William R., additional, and Wilson, Ian A., additional

Published
2017
Full Text
View/download PDF

36. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens

Author

Schiffner, Torben, primary, de Val, Natalia, additional, Russell, Rebecca A., additional, de Taeye, Steven W., additional, de la Peña, Alba Torrents, additional, Ozorowski, Gabriel, additional, Kim, Helen J., additional, Nieusma, Travis, additional, Brod, Florian, additional, Cupo, Albert, additional, Sanders, Rogier W., additional, Moore, John P., additional, Ward, Andrew B., additional, and Sattentau, Quentin J., additional

Published
2016
Full Text
View/download PDF

40. Comparison of Neutralizing Antibody Responses Elicited from Highly Diverse Polyvalent Heterotrimeric HIV-1 gp140 Cocktail Immunogens versus a Monovalent Counterpart in Rhesus Macaques

Author

Bowles, Emma J., primary, Schiffner, Torben, additional, Rosario, Maximillian, additional, Needham, Gemma A., additional, Ramaswamy, Meghna, additional, McGouran, Joanna, additional, Kessler, Benedikt, additional, LaBranche, Celia, additional, McMichael, Andrew J., additional, Montefiori, David, additional, Sattentau, Quentin J., additional, Hanke, Tomáš, additional, and Stewart-Jones, Guillaume B. E., additional

Published
2014
Full Text
View/download PDF

41. Refocussing Antibody Responses by Chemical Modification of Vaccine Antigens

Author

Schiffner, Torben, primary, Leonavicius, Karolis, additional, Schuster, Heiko, additional, Kim, Helen J., additional, Kong, Leopold, additional, Saliba, Regis, additional, Brod, Florian, additional, Wegmann, Frank, additional, Huang, Po-Ssu, additional, Stewart-Jones, Guillaume B., additional, Schief, William R., additional, Ward, Andrew B., additional, Moore, John P., additional, Sanders, Rogier W., additional, Davis, Benjamin G., additional, and Sattentau, Quentin J., additional

Published
2014
Full Text
View/download PDF

43. Boosting of HIV-1 Neutralizing Antibody Responses by a Distally Related Retroviral Envelope Protein

Author

Uchtenhagen, Hannes, primary, Schiffner, Torben, additional, Bowles, Emma, additional, Heyndrickx, Leo, additional, LaBranche, Celia, additional, Applequist, Steven E., additional, Jansson, Marianne, additional, De Silva, Thushan, additional, Back, Jaap Willem, additional, Achour, Adnane, additional, Scarlatti, Gabriella, additional, Fomsgaard, Anders, additional, Montefiori, David, additional, Stewart-Jones, Guillaume, additional, and Spetz, Anna-Lena, additional

Published
2014
Full Text
View/download PDF

47. Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates.

Author

Steichen JM, Phung I, Salcedo E, Ozorowski G, Willis JR, Baboo S, Liguori A, Cottrell CA, Torres JL, Madden PJ, Ma KM, Sutton HJ, Lee JH, Kalyuzhniy O, Allen JD, Rodriguez OL, Adachi Y, Mullen TM, Georgeson E, Kubitz M, Burns A, Barman S, Mopuri R, Metz A, Altheide TK, Diedrich JK, Saha S, Shields K, Schultze SE, Smith ML, Schiffner T, Burton DR, Watson CT, Bosinger SE, Crispin M, Yates JR 3rd, Paulson JC, Ward AB, Sok D, Crotty S, and Schief WR

Subjects
Animals, Humans, B-Lymphocytes immunology, Cryoelectron Microscopy, env Gene Products, Human Immunodeficiency Virus immunology, HIV Infections immunology, HIV Infections prevention & control, HIV-1 immunology, Immunoglobulin Heavy Chains immunology, Immunoglobulin Heavy Chains genetics, Macaca mulatta, Memory B Cells immunology, AIDS Vaccines immunology, Broadly Neutralizing Antibodies immunology, Complementarity Determining Regions immunology, Germinal Center immunology, HIV Antibodies immunology
Abstract

Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to HIV and other pathogens. However, antibody-antigen recognition is typically dominated by heavy chain complementarity determining region 3 (HCDR3) interactions, and vaccine priming of HCDR3-dominant bnAbs by germline-targeting immunogens has not been demonstrated in humans or outbred animals. In this work, immunization with N332-GT5, an HIV envelope trimer designed to target precursors of the HCDR3-dominant bnAb BG18, primed bnAb-precursor B cells in eight of eight rhesus macaques to substantial frequencies and with diverse lineages in germinal center and memory B cells. We confirmed bnAb-mimicking, HCDR3-dominant, trimer-binding interactions with cryo-electron microscopy. Our results demonstrate proof of principle for HCDR3-dominant bnAb-precursor priming in outbred animals and suggest that N332-GT5 holds promise for the induction of similar responses in humans.

Published
2024
Full Text
View/download PDF

48. DeGlyPHER: Highly sensitive site-specific analysis of N-linked glycans on proteins.

Author

Baboo S, Diedrich JK, Martínez-Bartolomé S, Wang X, Schiffner T, Groschel B, Schief WR, Paulson JC, and Yates JR 3rd

Subjects
Glycosylation, Polysaccharides metabolism, Mass Spectrometry, Spike Glycoprotein, Coronavirus metabolism, Glycoproteins metabolism
Abstract

Traditional mass spectrometry-based glycoproteomic approaches have been widely used for site-specific N-glycoform analysis, but a large amount of starting material is needed to obtain sampling that is representative of the vast diversity of N-glycans on glycoproteins. These methods also often include a complicated workflow and very challenging data analysis. These limitations have prevented glycoproteomics from being adapted to high-throughput platforms, and the sensitivity of the analysis is currently inadequate for elucidating N-glycan heterogeneity in clinical samples. Heavily glycosylated spike proteins of enveloped viruses, recombinantly expressed as potential vaccines, are prime targets for glycoproteomic analysis. Since the immunogenicity of spike proteins may be impacted by their glycosylation patterns, site-specific analysis of N-glycoforms provides critical information for vaccine design. Using recombinantly expressed soluble HIV Env trimer, we describe DeGlyPHER, a modification of our previously reported sequential deglycosylation strategy to yield a "single-pot" process. DeGlyPHER is an ultrasensitive, simple, rapid, robust, and efficient approach for site-specific analysis of protein N-glycoforms, that we developed for analysis of limited quantities of glycoproteins., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Published
2023
Full Text
View/download PDF

49. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens.

Author

Schiffner T, de Val N, Russell RA, de Taeye SW, de la Peña AT, Ozorowski G, Kim HJ, Nieusma T, Brod F, Cupo A, Sanders RW, Moore JP, Ward AB, and Sattentau QJ

Subjects
Antibodies, Neutralizing immunology, Cross-Linking Reagents metabolism, HIV Antibodies immunology, Humans, HIV Antigens immunology, HIV Antigens metabolism, HIV-1 immunology, env Gene Products, Human Immunodeficiency Virus immunology, env Gene Products, Human Immunodeficiency Virus metabolism
Abstract

Unlabelled: Major neutralizing antibody immune evasion strategies of the HIV-1 envelope glycoprotein (Env) trimer include conformational and structural instability. Stabilized soluble trimers such as BG505 SOSIP.664 mimic the structure of virion-associated Env but nevertheless sample different conformational states. Here we demonstrate that treating BG505 SOSIP.664 trimers with glutaraldehyde or a heterobifunctional cross-linker introduces additional stability with relatively modest effects on antigenicity. Thus, most broadly neutralizing antibody (bNAb) epitopes were preserved after cross-linking, whereas the binding of most weakly or nonneutralizing antibodies (non-NAb) was reduced. Cross-linking stabilized all Env conformers present within a mixed population, and individual conformers could be isolated by bNAb affinity chromatography. Both positive selection of cross-linked conformers using the quaternary epitope-specific bNAbs PGT145, PGT151, and 3BC315 and negative selection with non-NAbs against the V3 region enriched for trimer populations with improved antigenicity for bNAbs. Similar results were obtained using the clade B B41 SOSIP.664 trimer. The cross-linking method may, therefore, be useful for countering the natural conformational heterogeneity of some HIV-1 Env proteins and, by extrapolation, also vaccine immunogens from other pathogens., Importance: The development of a vaccine to induce protective antibodies against HIV-1 is of primary public health importance. Recent advances in immunogen design have provided soluble recombinant envelope glycoprotein trimers with near-native morphology and antigenicity. However, these trimers are conformationally flexible, potentially reducing B-cell recognition of neutralizing antibody epitopes. Here we show that chemical cross-linking increases trimer stability, reducing binding of nonneutralizing antibodies while largely maintaining neutralizing antibody binding. Cross-linking followed by positive or negative antibody affinity selection of individual stable conformational variants further improved the antigenic and morphological characteristics of the trimers. This approach may be generally applicable to HIV-1 Env and also to other conformationally flexible pathogen antigens., (Copyright © 2015 Schiffner et al.)

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results