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1. Three immunizations with Novavax’s protein vaccines increase antibody breadth and provide durable protection from SARS-CoV-2

Author

Lenart, Klara, Arcoverde Cerveira, Rodrigo, Hellgren, Fredrika, Ols, Sebastian, Sheward, Daniel J., Kim, Changil, Cagigi, Alberto, Gagne, Matthew, Davis, Brandon, Germosen, Daritza, Roy, Vicky, Alter, Galit, Letscher, Hélène, Van Wassenhove, Jérôme, Gros, Wesley, Gallouët, Anne-Sophie, Le Grand, Roger, Kleanthous, Harry, Guebre-Xabier, Mimi, Murrell, Ben, Patel, Nita, Glenn, Gregory, Smith, Gale, and Loré, Karin

Published
2024
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4. Immunogenicity and protective efficacy of GBP510/AS03 vaccine against SARS-CoV-2 delta challenge in rhesus macaques

Author

Jacob-Dolan, Catherine, Yu, Jingyou, McMahan, Katherine, Giffin, Victoria, Chandrashekar, Abishek, Martinot, Amanda J., Anioke, Tochi, Powers, Olivia C., Hall, Kevin, Hope, David, Miller, Jessica, Hachmann, Nichole P., Chung, Benjamin, Gardner, Sarah, Sellers, Daniel, Barrett, Julia, Lewis, Mark G., Andersen, Hanne, Kleanthous, Harry, Seo, Ki-Woen, Lee, Su Jeen, Park, Yong Wook, Kim, Hun, and Barouch, Dan H.

Published
2023
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6. Molecular engineering of a cryptic epitope in Spike RBD improves manufacturability and neutralizing breadth against SARS-CoV-2 variants

Author

Rodriguez-Aponte, Sergio A., Dalvie, Neil C., Wong, Ting Y., Johnston, Ryan S., Naranjo, Christopher A., Bajoria, Sakshi, Kumru, Ozan S., Kaur, Kawaljit, Russ, Brynnan P., Lee, Katherine S., Cyphert, Holly A., Barbier, Mariette, Rao, Harish D., Rajurkar, Meghraj P., Lothe, Rakesh R., Shaligram, Umesh S., Batwal, Saurabh, Chandrasekaran, Rahul, Nagar, Gaurav, Kleanthous, Harry, Biswas, Sumi, Bevere, Justin R., Joshi, Sangeeta B., Volkin, David B., Damron, F. Heath, and Love, J. Christopher

Published
2023
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7. Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice

Author

Dalvie, Neil C., Rodriguez-Aponte, Sergio A., Hartwell, Brittany L., Tostanoski, Lisa H., Biedermann, Andrew M., Crowell, Laura E., Kaur, Kawaljit, Kumru, Ozan S., Carter, Lauren, Yu, Jingyou, Chang, Aiquan, McMahan, Katherine, Courant, Thomas, Lebas, Celia, Lemnios, Ashley A., Rodrigues, Kristen A., Silva, Murillo, Johnston, Ryan S., Naranjo, Christopher A., Tracey, Mary Kate, Brady, Joseph R., Whittaker, Charles A., Yun, Dongsoo, Brunette, Natalie, Wang, Jing Yang, Walkey, Carl, Fiala, Brooke, Kar, Swagata, Porto, Maciel, Lok, Megan, Andersen, Hanne, Lewis, Mark G., Love, Kerry R., Camp, Danielle L., Silverman, Judith Maxwell, Kleanthous, Harry, Joshi, Sangeeta B., Volkin, David B., Dubois, Patrice M., Collin, Nicolas, King, Neil P., Barouch, Dan H., Irvine, Darrell J., and Love, J. Christopher

Published
2021

9. Adjuvanting a subunit SARS-CoV-2 vaccine with clinically relevant adjuvants induces durable protection in mice

Author

Grigoryan, Lilit, Lee, Audrey, Walls, Alexandra C., Lai, Lilin, Franco, Benjamin, Arunachalam, Prabhu S., Feng, Yupeng, Luo, Wei, Vanderheiden, Abigail, Floyd, Katharine, Wrenn, Samuel, Pettie, Deleah, Miranda, Marcos C., Kepl, Elizabeth, Ravichandran, Rashmi, Sydeman, Claire, Brunette, Natalie, Murphy, Michael, Fiala, Brooke, Carter, Lauren, Coffman, Robert L., Novack, David, Kleanthous, Harry, O’Hagan, Derek T., van der Most, Robbert, McLellan, Jason S., Suthar, Mehul, Veesler, David, King, Neil P., and Pulendran, Bali

Published
2022
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10. Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines

Author

Walls, Alexandra C., Miranda, Marcos C., Schäfer, Alexandra, Pham, Minh N., Greaney, Allison, Arunachalam, Prabhu S., Navarro, Mary-Jane, Tortorici, M. Alejandra, Rogers, Kenneth, O’Connor, Megan A., Shirreff, Lisa, Ferrell, Douglas E., Bowen, John, Brunette, Natalie, Kepl, Elizabeth, Zepeda, Samantha K., Starr, Tyler, Hsieh, Ching-Lin, Fiala, Brooke, Wrenn, Samuel, Pettie, Deleah, Sydeman, Claire, Sprouse, Kaitlin R., Johnson, Max, Blackstone, Alyssa, Ravichandran, Rashmi, Ogohara, Cassandra, Carter, Lauren, Tilles, Sasha W., Rappuoli, Rino, Leist, Sarah R., Martinez, David R., Clark, Matthew, Tisch, Roland, O’Hagan, Derek T., Van Der Most, Robbert, Van Voorhis, Wesley C., Corti, Davide, McLellan, Jason S., Kleanthous, Harry, Sheahan, Timothy P., Smith, Kelly D., Fuller, Deborah H., Villinger, Francois, Bloom, Jesse, Pulendran, Bali, Baric, Ralph S., King, Neil P., and Veesler, David

Published
2021
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11. Adjuvanting a subunit COVID-19 vaccine to induce protective immunity

Author

Arunachalam, Prabhu S., Walls, Alexandra C., Golden, Nadia, Atyeo, Caroline, Fischinger, Stephanie, Li, Chunfeng, Aye, Pyone, Navarro, Mary Jane, Lai, Lilin, Edara, Venkata Viswanadh, Röltgen, Katharina, Rogers, Kenneth, Shirreff, Lisa, Ferrell, Douglas E., Wrenn, Samuel, Pettie, Deleah, Kraft, John C., Miranda, Marcos C., Kepl, Elizabeth, Sydeman, Claire, Brunette, Natalie, Murphy, Michael, Fiala, Brooke, Carter, Lauren, White, Alexander G., Trisal, Meera, Hsieh, Ching-Lin, Russell-Lodrigue, Kasi, Monjure, Christopher, Dufour, Jason, Spencer, Skye, Doyle-Meyers, Lara, Bohm, Rudolph P., Maness, Nicholas J., Roy, Chad, Plante, Jessica A., Plante, Kenneth S., Zhu, Alex, Gorman, Matthew J., Shin, Sally, Shen, Xiaoying, Fontenot, Jane, Gupta, Shakti, O’Hagan, Derek T., Van Der Most, Robbert, Rappuoli, Rino, Coffman, Robert L., Novack, David, McLellan, Jason S., Subramaniam, Shankar, Montefiori, David, Boyd, Scott D., Flynn, JoAnne L., Alter, Galit, Villinger, Francois, Kleanthous, Harry, Rappaport, Jay, Suthar, Mehul S., King, Neil P., Veesler, David, and Pulendran, Bali

Published
2021
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14. Effects of aluminum-salt, CpG and emulsion adjuvants on the stability and immunogenicity of a virus-like particle displaying the SARS-CoV-2 receptor-binding domain (RBD)

Author

Kumru, Ozan S., primary, Bajoria, Sakshi, additional, Kaur, Kawaljit, additional, Hickey, John M., additional, Van Slyke, Greta, additional, Doering, Jennifer, additional, Berman, Katherine, additional, Richardson, Charles, additional, Lien, Hans, additional, Kleanthous, Harry, additional, Mantis, Nicholas J., additional, Joshi, Sangeeta B., additional, and Volkin, David B., additional

Published
2023
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15. Effects of aluminum-salt, CpG and emulsion adjuvants on the stability and immunogenicity of a virus-like particle displaying the SARS-CoV-2 receptor binding domain (RBD)

Author

Kumru, Ozan S, primary, Bajoria, Sakshi, additional, Kaur, Kawaljit, additional, Hickey, John M, additional, Van Slyke, Greta, additional, Doering, Jennifer, additional, Berman, Katherine, additional, Richardson, Charles, additional, Lien, Hans, additional, Kleanthous, Harry, additional, Mantis, Nicholas J, additional, Joshi, Sangeeta B, additional, and Volkin, David B, additional

Published
2023
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16. Incorporation of RG1 epitope concatemers into a self-adjuvanting Flagellin-L2 vaccine broaden durable protection against cutaneous challenge with diverse human papillomavirus genotypes

Author

Kalnin, Kirill, Chivukula, Sudha, Tibbitts, Timothy, Yan, Yanhua, Stegalkina, Svetlana, Shen, Lihua, Cieszynski, Jacqueline, Costa, Victor, Sabharwal, Robert, Anderson, Stephen F., Christensen, Neil, Jagu, Subhashini, Roden, Richard B.S., and Kleanthous, Harry

Published
2017
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17. Influenza vaccination in the elderly boosts antibodies against conserved viral proteins and egg-produced glycans

Author

Jung, Jiwon, Mundle, Sophia T., Ustyugova, Irina V., Horton, Andrew P., Boutz, Daniel R., Pougatcheva, Svetlana, Prabakaran, Ponraj, King, Jonathan R. McDanie Gregory R., Park, Daechan, Person, Maria D., Ye, Congxi, Tan, Bing, Tanno, Yuri, Kim, Jin Eyun, Curtis, Nicholas C., DiNapoli, Joshua, Delagrave, Simon, Ross, Ted M., Ippolito, Gregory C., Kleanthous, Harry, Lee, Jiwon, and Georgiou, George

Subjects
Antigen-antibody reactions -- Health aspects, Aged -- Care and treatment -- Physiological aspects, Influenza vaccines -- Patient outcomes, Immune response -- Health aspects, Influenza -- Risk factors -- Prevention, Health care industry
Abstract

Seasonal influenza vaccination elicits a diminished adaptive immune response in the elderly, and the mechanisms of immunosenescence are not fully understood. Using Ig-Seq, we found a marked increase with age in the prevalence of crossreactive (CR) serum antibodies that recognize both the H1N1 (vaccine-H1) and H3N2 (vaccine-H3) components of an egg- produced split influenza vaccine. CR antibodies accounted for 73% [+ or -] 18% of the serum vaccine responses in a cohort of elderly donors, 65% [+ or -] 15% in late middle-aged donors, and only 13% [+ or -] 5% in persons under 35 years of age. The antibody response to non-HA antigens was boosted by vaccination. Recombinant expression of 19 vaccine-H1+H3 CR serum monoclonal antibodies (s-mAbs) revealed that they predominantly bound to non-HA influenza proteins. A sizable fraction of vaccineH1+H3 CR s-mAbs recognized with high affinity the sulfated glycans, in particular sulfated type 2 N-acetyllactosamine (Gal[beta]1-4GalNAc[beta]), which is found on egg-produced proteins and thus unlikely to contribute to protection against influenza infection in humans. Antibodies against sulfated glycans in egg-produced vaccine had been identified in animals but were not previously characterized in humans. Collectively, our results provide a quantitative basis for how repeated exposure to split influenza vaccine correlates with unintended focusing of serum antibody responses to non-HA antigens that may result in suboptimal immunity against influenza., Introduction Influenza is a serious global health threat causing nearly 5 million severe cases of illness and 650,000 deaths annually and particularly affecting individuals aged 65 years or older (1,2). [...]

Published
2021
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18. Nanoalum Formulations Containing Aluminum Hydroxide and Cpg 1018TM Adjuvants: The Effect on Stability and Immunogen-Icity of a Recombinant SARS-CoV-2 Rbd Antigen

Author

Bajoria, Sakshi, primary, Kumru, Ozan S., additional, Doering, Jennifer, additional, Berman, Katherine, additional, Slyke, Greta Van, additional, Prigodich, Anneka, additional, Rodriguez-Aponte, Sergio A., additional, Kleanthous, Harry, additional, Love, J. Christopher, additional, Mantis, Nicholas J., additional, Joshi, Sangeeta B., additional, and Volkin, David B., additional

Published
2023
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19. Broadly neutralizing antibodies against sarbecoviruses generated by immunization of macaques with an AS03-adjuvanted COVID-19 vaccine

Author

Feng, Yupeng, primary, Yuan, Meng, additional, Powers, John M., additional, Hu, Mengyun, additional, Munt, Jennifer E., additional, Arunachalam, Prabhu S., additional, Leist, Sarah R., additional, Bellusci, Lorenza, additional, Kim, JungHyun, additional, Sprouse, Kaitlin R., additional, Adams, Lily E., additional, Sundaramurthy, Sumana, additional, Zhu, Xueyong, additional, Shirreff, Lisa M., additional, Mallory, Michael L., additional, Scobey, Trevor D., additional, Moreno, Alberto, additional, O’Hagan, Derek T., additional, Kleanthous, Harry, additional, Villinger, Francois J., additional, Veesler, David, additional, King, Neil P., additional, Suthar, Mehul S., additional, Khurana, Surender, additional, Baric, Ralph S., additional, Wilson, Ian A., additional, and Pulendran, Bali, additional

Published
2023
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21. Enhanced protective efficacy of a novel, thermostable, RBD-S2 fusion immunogen against SARS-CoV-2 and its variants

Author

Mittal, Nidhi, primary, Kumar, Sahil, additional, Rajmani, Raju S, additional, Singh, Randhir, additional, Lemoine, Celine, additional, Jakob, Virginie, additional, BJ, Sowrabha, additional, Bhat, Madhuraj, additional, Chakraborty, Debajyoti, additional, Pandey, Suman, additional, Jory, Aurelie, additional, S.A., Suba Soundarya, additional, Kleanthous, Harry, additional, Dubois, Patrice, additional, Ringe, Rajesh P, additional, and Varadarajan, Raghavan, additional

Published
2023
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22. Nanoalum Formulations Containing Aluminum Hydroxide and CpG 1018TM Adjuvants: The Effect on Stability and Immunogenicity of a Recombinant SARS-CoV-2 RBD Antigen

Author

Massachusetts Institute of Technology. Department of Biological Engineering, Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Chemical Engineering, Bajoria, Sakshi, Kumru, Ozan S., Doering, Jennifer, Berman, Katherine, Slyke, Greta Van, Prigodich, Anneka, Rodriguez-Aponte, Sergio A., Kleanthous, Harry, Love, J. Christopher, Mantis, Nicholas J., Joshi, Sangeeta B., Volkin, David B., Massachusetts Institute of Technology. Department of Biological Engineering, Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Chemical Engineering, Bajoria, Sakshi, Kumru, Ozan S., Doering, Jennifer, Berman, Katherine, Slyke, Greta Van, Prigodich, Anneka, Rodriguez-Aponte, Sergio A., Kleanthous, Harry, Love, J. Christopher, Mantis, Nicholas J., Joshi, Sangeeta B., and Volkin, David B.

Abstract

Aluminum-salt vaccine adjuvants (alum) are commercially available as micron-sized particles with varying chemical composition and crystallinity. There are reports of enhanced adjuvanticity when the alum’s particle size is reduced to the nanometer range. Previously, we demonstrated that a recombinant receptor-binding domain (RBD)-based COVID-19 vaccine candidate (RBD-J; RBD-L452K-F490W) formulated with aluminum hydroxide (Alhydrogel®; AH) and CpG 1018™ (CpG) adjuvants induced potent neutralizing antibody responses in mice yet displayed instability during storage. In this work, we evaluated whether sonication of AH to the nanometer size range (nanoAH) could further enhance immunogenicity or improve storage stability of the above formulation. The addition of CpG to nanoAH (at mouse doses), however, caused re-agglomeration of nanoAH. AH-CpG interactions were evaluated by Langmuir binding isotherms and zeta potential measurements, and stabilized nanoAH + CpG formulations of RBD-J were then designed by (1) optimizing CpG:Aluminum dose ratios or (2) adding a small-molecule polyanion (phytic acid, PA). Compared with the micron-sized AH + CpG formulation, the two stabilized nanoAH + CpG formulations of RBD-J demonstrated no enhancement in SARS-CoV-2 pseudovirus neutralizing titers in mice, but the PA-containing nanoAH + CpG formulation showed improved RBD-J storage stability trends (at 4, 25, and 37 °C). The formulation protocols presented herein can be employed to evaluate the potential benefits of the nanoAH + CpG adjuvant combination with other vaccine antigens in different animal models.

Published
2023

24. Extremely potent pan-sarbecovirus neutralizing antibodies generated by immunization of macaques with an AS03-adjuvanted monovalent subunit vaccine against SARS-CoV-2

Author

Feng, Yupeng, primary, Yuan, Meng, additional, Powers, John M., additional, Hu, Mengyun, additional, Munt, Jennifer E., additional, Arunachalam, Prabhu S., additional, Leist, Sarah R., additional, Bellusci, Lorenza, additional, Adams, Lily E., additional, Sundaramurthy, Sumana, additional, Shirreff, Lisa M., additional, Mallory, Michael L., additional, Scooby, Trevor D., additional, Moreno, Alberto, additional, O’Hagan, Derek T., additional, Kleanthous, Harry, additional, Villinger, Francois J., additional, Veesler, David, additional, King, Neil P., additional, Suthar, Mehul S., additional, Khurana, Surender, additional, Baric, Ralph S., additional, Wilson, Ian A., additional, and Pulendran, Bali, additional

Published
2023
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26. Extremely potent pan-sarbecovirus neutralizing antibodies generated by immunization of macaques with an AS03-adjuvanted monovalent subunit vaccine against SARS-CoV-2

Author

Feng, Yupeng, Yuan, Meng, Powers, John M., Hu, Mengyun, Munt, Jennifer E., Arunachalam, Prabhu S., Leist, Sarah R., Bellusci, Lorenza, Adams, Lily E., Sundaramurthy, Sumana, Shirreff, Lisa M., Mallory, Michael L., Scooby, Trevor D., Moreno, Alberto, O’Hagan, Derek T., Kleanthous, Harry, Villinger, Francois J., Veesler, David, King, Neil P., Suthar, Mehul S., Khurana, Surender, Baric, Ralph S., Wilson, Ian A., and Pulendran, Bali

Subjects
Article
Abstract

The rapid emergence of SARS-CoV-2 variants that evade immunity to vaccination has placed a global health imperative on the development of therapeutic countermeasures that provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent pan-sarbecovirus antibodies from non-human primates vaccinated with an AS03 adjuvanted subunit vaccine against SARS-CoV-2 that recognize conserved epitopes in the receptor binding domain (RBD) with femtomolar affinities. Longitudinal analysis revealed progressive accumulation of somatic mutation in the immunoglobulin genes of antigen-specific memory B cells for at least one year following primary vaccination. 514 monoclonal antibodies (mAbs) were generated from antigen-specific memory B cells. Antibodies isolated at 5 to 12 months following vaccination displayed greater potency and breadth, relative to those identified at 1.4 months. Notably, 15 out of 338 (∼4.4%) antibodies isolated at 1.4∼6 months after the primary vaccination showed extraordinary neutralization potency against SARS-CoV-2 omicron BA.1, despite the absence of BA.1 neutralization in serum. Two of them, 25F9 and 20A7, neutralized authentic clade Ia sarbecoviruses (SARS-CoV, WIV-1, SHC014) and clade Ib sarbecoviruses (SARS-CoV-2 D614G, SARS-CoV-2 BA.1, Pangolin-GD) with half-maximal inhibition concentrations of (0.85 ng/ml, 3 ng/ml, 6 ng/ml, 6 ng/ml, 42 ng/ml, 6 ng/ml) and (13 ng/ml, 2 ng/ml, 18 ng/ml, 9 ng/ml, 6 ng/ml, 345 ng/ml), respectively. Furthermore, 20A7 and 27A12 showed potent neutralization against all SARS-CoV-2 variants of concern and multiple Omicron sublineages, including BA.1, BA.2, BA.3, BA.4/5, BQ.1, BQ.1.1 and XBB variants. X-ray crystallography studies revealed the molecular basis of broad and potent neutralization through targeting conserved RBD sites. In vivo prophylactic protection of 25F9, 20A7 and 27A12 was confirmed in aged Balb/c mice. Notably, administration of 25F9 provided complete protection against SARS-CoV-2, SARS-CoV-2 BA.1, SARS-CoV, and SHC014 challenge, underscoring that these mAbs are promising pan-sarbecovirus therapeutic antibodies.One Sentence SummaryExtremely potent pan-sarbecovirus neutralizing antibodies

Published
2023

27. Molecular engineering of a cryptic epitope in Spike RBD improves manufacturability and neutralizing breadth against SARS-CoV-2 variants

Author

Rodriguez-Aponte, Sergio A., primary, Dalvie, Neil C., additional, Wong, Ting Y., additional, Johnston, Ryan S., additional, Naranjo, Christopher A., additional, Bajoria, Sakshi, additional, Kumru, Ozan S., additional, Kaur, Kawaljit, additional, Russ, Brynnan P., additional, Lee, Katherine S., additional, Cyphert, Holly A., additional, Barbier, Mariette, additional, Rao, Harish D., additional, Rajurkar, Meghraj P., additional, Lothe, Rakesh R., additional, Shaligram, Umesh S., additional, Batwal, Saurabh, additional, Chandrasekaran, Rahul, additional, Nagar, Gaurav, additional, Kleanthous, Harry, additional, Biswas, Sumi, additional, Bevere, Justin R., additional, Joshi, Sangeeta B., additional, Volkin, David B., additional, Damron, F. Heath, additional, and Love, J. Christopher, additional

Published
2022
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28. A multimechanistic antibody targeting the receptor binding site potently cross-protects against influenza B viruses

Author

Shen, Chenguang, Chen, Junyu, Li, Rui, Zhang, Mengya, Wang, Guosong, Stegalkina, Svetlana, Zhang, Limin, Chen, Jing, Cao, Jianli, Bi, Xingjian, Anderson, Stephen F., Alefantis, Timothy, Zhang, Minwei, Cai, Xiaoyang, Yang, Kunyu, Zheng, Qingbing, Fang, Mujing, Yu, Hai, Luo, Wenxin, Zheng, Zizheng, Yuan, Quan, Zhang, Jun, Wai-Kuo Shih, James, Kleanthous, Harry, Chen, Honglin, Chen, Yixin, and Xia, Ningshao

Published
2017
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29. Nanoalum Formulations Containing Aluminum Hydroxide and CpG 1018 TM Adjuvants: The Effect on Stability and Immunogenicity of a Recombinant SARS-CoV-2 RBD Antigen.

Author

Bajoria, Sakshi, Kumru, Ozan S., Doering, Jennifer, Berman, Katherine, Slyke, Greta Van, Prigodich, Anneka, Rodriguez-Aponte, Sergio A., Kleanthous, Harry, Love, J. Christopher, Mantis, Nicholas J., Joshi, Sangeeta B., and Volkin, David B.

Subjects
ALUMINUM hydroxide, IMMUNE response, COMBINED vaccines, SARS-CoV-2, PHYTIC acid, TITERS
Abstract

Aluminum-salt vaccine adjuvants (alum) are commercially available as micron-sized particles with varying chemical composition and crystallinity. There are reports of enhanced adjuvanticity when the alum's particle size is reduced to the nanometer range. Previously, we demonstrated that a recombinant receptor-binding domain (RBD)-based COVID-19 vaccine candidate (RBD-J; RBD-L452K-F490W) formulated with aluminum hydroxide (Alhydrogel®; AH) and CpG 1018™ (CpG) adjuvants induced potent neutralizing antibody responses in mice yet displayed instability during storage. In this work, we evaluated whether sonication of AH to the nanometer size range (nanoAH) could further enhance immunogenicity or improve storage stability of the above formulation. The addition of CpG to nanoAH (at mouse doses), however, caused re-agglomeration of nanoAH. AH-CpG interactions were evaluated by Langmuir binding isotherms and zeta potential measurements, and stabilized nanoAH + CpG formulations of RBD-J were then designed by (1) optimizing CpG:Aluminum dose ratios or (2) adding a small-molecule polyanion (phytic acid, PA). Compared with the micron-sized AH + CpG formulation, the two stabilized nanoAH + CpG formulations of RBD-J demonstrated no enhancement in SARS-CoV-2 pseudovirus neutralizing titers in mice, but the PA-containing nanoAH + CpG formulation showed improved RBD-J storage stability trends (at 4, 25, and 37 °C). The formulation protocols presented herein can be employed to evaluate the potential benefits of the nanoAH + CpG adjuvant combination with other vaccine antigens in different animal models. [ABSTRACT FROM AUTHOR]

Published
2023
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30. Durable protection against the SARS-CoV-2 Omicron variant is induced by an adjuvanted subunit vaccine

Author

Arunachalam, Prabhu S., primary, Feng, Yupeng, additional, Ashraf, Usama, additional, Hu, Mengyun, additional, Walls, Alexandra C., additional, Edara, Venkata Viswanadh, additional, Zarnitsyna, Veronika I., additional, Aye, Pyone Pyone, additional, Golden, Nadia, additional, Miranda, Marcos C., additional, Green, Kristyn W. M., additional, Threeton, Breanna M., additional, Maness, Nicholas J., additional, Beddingfield, Brandon J., additional, Bohm, Rudolf P., additional, Scheuermann, Sarah E., additional, Goff, Kelly, additional, Dufour, Jason, additional, Russell-Lodrigue, Kasi, additional, Kepl, Elizabeth, additional, Fiala, Brooke, additional, Wrenn, Samuel, additional, Ravichandran, Rashmi, additional, Ellis, Daniel, additional, Carter, Lauren, additional, Rogers, Kenneth, additional, Shirreff, Lisa M., additional, Ferrell, Douglas E., additional, Deb Adhikary, Nihar R., additional, Fontenot, Jane, additional, Hammond, Holly L., additional, Frieman, Matthew, additional, Grifoni, Alba, additional, Sette, Alessandro, additional, O’Hagan, Derek T., additional, Van Der Most, Robbert, additional, Rappuoli, Rino, additional, Villinger, Francois, additional, Kleanthous, Harry, additional, Rappaport, Jay, additional, Suthar, Mehul S., additional, Veesler, David, additional, Wang, Taia T., additional, King, Neil P., additional, and Pulendran, Bali, additional

Published
2022
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31. Antigen-adjuvant interactions, stability, and immunogenicity profiles of a SARS-CoV-2 receptor-binding domain (RBD) antigen formulated with aluminum salt and CpG adjuvants

Author

Bajoria, Sakshi, primary, Kaur, Kawaljit, additional, Kumru, Ozan S., additional, Van Slyke, Greta, additional, Doering, Jennifer, additional, Novak, Hayley, additional, Rodriguez Aponte, Sergio A., additional, Dalvie, Neil C., additional, Naranjo, Christopher A., additional, Johnston, Ryan S., additional, Silverman, Judith Maxwell, additional, Kleanthous, Harry, additional, Love, J. Christopher, additional, Mantis, Nicholas J., additional, Joshi, Sangeeta B., additional, and Volkin, David B., additional

Published
2022
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33. Durable protection against SARS-CoV-2 Omicron induced by an adjuvanted subunit vaccine

Author

Arunachalam, Prabhu S., primary, Feng, Yupeng, additional, Ashraf, Usama, additional, Hu, Mengyun, additional, Edara, Venkata Viswanadh, additional, Zarnitsyna, Veronika I., additional, Aye, Pyone Pyone, additional, Golden, Nadia, additional, Green, Kristyn W. M., additional, Threeton, Breanna M., additional, Maness, Nicholas J., additional, Beddingfield, Brandon J., additional, Bohm, Rudolf P., additional, Dufour, Jason, additional, Russell-Lodrigue, Kasi, additional, Miranda, Marcos C., additional, Walls, Alexandra C., additional, Rogers, Kenneth, additional, Shirreff, Lisa, additional, Ferrell, Douglas E, additional, Deb Adhikary, Nihar R., additional, Fontenot, Jane, additional, Grifoni, Alba, additional, Sette, Alessandro, additional, O’Hagan, Derek T., additional, Van Der Most, Robbert, additional, Rappuoli, Rino, additional, Villinger, Francois, additional, Kleanthous, Harry, additional, Rappaport, Jay, additional, Suthar, Mehul S., additional, Veesler, David, additional, Wang, Taia T., additional, King, Neil P., additional, and Pulendran, Bali, additional

Published
2022
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34. SARS-CoV-2 receptor binding domain displayed on HBsAg virus–like particles elicits protective immunity in macaques

Author

Dalvie, Neil C., primary, Tostanoski, Lisa H., additional, Rodriguez-Aponte, Sergio A., additional, Kaur, Kawaljit, additional, Bajoria, Sakshi, additional, Kumru, Ozan S., additional, Martinot, Amanda J., additional, Chandrashekar, Abishek, additional, McMahan, Katherine, additional, Mercado, Noe B., additional, Yu, Jingyou, additional, Chang, Aiquan, additional, Giffin, Victoria M., additional, Nampanya, Felix, additional, Patel, Shivani, additional, Bowman, Lesley, additional, Naranjo, Christopher A., additional, Yun, Dongsoo, additional, Flinchbaugh, Zach, additional, Pessaint, Laurent, additional, Brown, Renita, additional, Velasco, Jason, additional, Teow, Elyse, additional, Cook, Anthony, additional, Andersen, Hanne, additional, Lewis, Mark G., additional, Camp, Danielle L., additional, Silverman, Judith Maxwell, additional, Nagar, Gaurav S., additional, Rao, Harish D., additional, Lothe, Rakesh R., additional, Chandrasekharan, Rahul, additional, Rajurkar, Meghraj P., additional, Shaligram, Umesh S., additional, Kleanthous, Harry, additional, Joshi, Sangeeta B., additional, Volkin, David B., additional, Biswas, Sumi, additional, Love, J. Christopher, additional, and Barouch, Dan H., additional

Published
2022
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36. Novel structural insights for a pair of monoclonal antibodies recognizing non-overlapping epitopes of the glucosyltransferase domain of Clostridium difficile toxin B

Author

Liu, Jinyu, primary, Kothe, Michael, additional, Zhang, Jianxin, additional, Oloo, Eliud, additional, Stegalkina, Svetlana, additional, Mundle, Sophia T., additional, Li, Lu, additional, Zhang, Jinrong, additional, Cole, Leah E., additional, Barone, Lucianna, additional, Biemann, Hans-Peter, additional, Kleanthous, Harry, additional, Anosova, Natalie G., additional, and Anderson, Stephen F., additional

Published
2022
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38. A modular protein subunit vaccine candidate produced in yeast confers protection against SARS-CoV-2 in non-human primates

Author

Dalvie, Neil C., primary, Tostanoski, Lisa H., additional, Rodriguez-Aponte, Sergio A, additional, Kaur, Kawaljit, additional, Bajoria, Sakshi, additional, Kumru, Ozan S., additional, Martinot, Amanda J., additional, Chandrashekar, Abishek, additional, McMahan, Katherine, additional, Mercado, Noe B., additional, Yu, Jingyou, additional, Chang, Aiquan, additional, Giffin, Victoria M., additional, Nampanya, Felix, additional, Patel, Shivani, additional, Bowman, Lesley, additional, Naranjo, Christopher A., additional, Yun, Dongsoo, additional, Flinchbaugh, Zach, additional, Pessaint, Laurent, additional, Brown, Renita, additional, Velasco, Jason, additional, Teow, Elyse, additional, Cook, Anthony, additional, Andersen, Hanne, additional, Lewis, Mark G., additional, Camp, Danielle L., additional, Silverman, Judith Maxwell, additional, Kleanthous, Harry, additional, Joshi, Sangeeta B., additional, Volkin, David B., additional, Biswas, Sumi, additional, Love, J. Christopher, additional, and Barouch, Dan H., additional

Published
2021
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39. Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice

Author

Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Biological Engineering, Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Dalvie, Neil C., Rodriguez-Aponte, Sergio A., Hartwell, Brittany L., Tostanoski, Lisa H., Biedermann, Andrew M., Crowell, Laura E, Kaur, Kawaljit, Kumru, Ozan S., Carter, Lauren, Yu, Jingyou, Chang, Aiquan, McMahan, Katherine, Courant, Thomas, Lebas, Celia, Lemnios, Ashley A., Rodrigues, Kristen A., Silva, Murillo, Johnston, Ryan S., Naranjo, Christopher, Tracey, Mary Kate, Brady, Joseph R., Whittaker, Charles A., Yun, Dongsoo, Brunette, Natalie, Wang, Jing Yang, Walkey, Carl, Fiala, Brooke, Kar, Swagata, Porto, Maciel, Lok, Megan, Andersen, Hanne, Lewis, Mark G., Love, Kerry R., Camp, Danielle L., Silverman, Judith Maxwell, Kleanthous, Harry, Joshi, Sangeeta B., Volkin, David B., Dubois, Patrice M., Collin, Nicolas, King, Neil P., Barouch, Dan H., Irvine, Darrell J, Love, Christopher J., Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Biological Engineering, Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Dalvie, Neil C., Rodriguez-Aponte, Sergio A., Hartwell, Brittany L., Tostanoski, Lisa H., Biedermann, Andrew M., Crowell, Laura E, Kaur, Kawaljit, Kumru, Ozan S., Carter, Lauren, Yu, Jingyou, Chang, Aiquan, McMahan, Katherine, Courant, Thomas, Lebas, Celia, Lemnios, Ashley A., Rodrigues, Kristen A., Silva, Murillo, Johnston, Ryan S., Naranjo, Christopher, Tracey, Mary Kate, Brady, Joseph R., Whittaker, Charles A., Yun, Dongsoo, Brunette, Natalie, Wang, Jing Yang, Walkey, Carl, Fiala, Brooke, Kar, Swagata, Porto, Maciel, Lok, Megan, Andersen, Hanne, Lewis, Mark G., Love, Kerry R., Camp, Danielle L., Silverman, Judith Maxwell, Kleanthous, Harry, Joshi, Sangeeta B., Volkin, David B., Dubois, Patrice M., Collin, Nicolas, King, Neil P., Barouch, Dan H., Irvine, Darrell J, and Love, Christopher J.

Abstract

Global containment of COVID-19 still requires accessible and affordable vaccines for low- and middle-income countries (LMICs). Recently approved vaccines provide needed interventions, albeit at prices that may limit their global access. Subunit vaccines based on recombinant proteins are suited for large-volume microbial manufacturing to yield billions of doses annually, minimizing their manufacturing cost. These types of vaccines are well-established, proven interventions with multiple safe and efficacious commercial examples. Many vaccine candidates of this type for SARS-CoV-2 rely on sequences containing the receptor-binding domain (RBD), which mediates viral entry to cells via ACE2. Here we report an engineered sequence variant of RBD that exhibits high-yield manufacturability, high-affinity binding to ACE2, and enhanced immunogenicity after a single dose in mice compared to the Wuhan-Hu-1 variant used in current vaccines. Antibodies raised against the engineered protein exhibited heterotypic binding to the RBD from two recently reported SARS-CoV-2 variants of concern (501Y.V1/V2). Presentation of the engineered RBD on a designed virus-like particle (VLP) also reduced weight loss in hamsters upon viral challenge.

Published
2021

40. Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines

Author

Walls, Alexandra C., primary, Miranda, Marcos C., additional, Pham, Minh N., additional, Schäfer, Alexandra, additional, Greaney, Allison, additional, Arunachalam, Prabhu S., additional, Navarro, Mary-Jane, additional, Tortorici, M. Alejandra, additional, Rogers, Kenneth, additional, O’Connor, Megan A., additional, Shireff, Lisa, additional, Ferrell, Douglas E., additional, Brunette, Natalie, additional, Kepl, Elizabeth, additional, Bowen, John, additional, Zepeda, Samantha K., additional, Starr, Tyler, additional, Hsieh, Ching-Lin, additional, Fiala, Brooke, additional, Wrenn, Samuel, additional, Pettie, Deleah, additional, Sydeman, Claire, additional, Johnson, Max, additional, Blackstone, Alyssa, additional, Ravichandran, Rashmi, additional, Ogohara, Cassandra, additional, Carter, Lauren, additional, Tilles, Sasha W., additional, Rappuoli, Rino, additional, O’Hagan, Derek T., additional, Van Der Most, Robbert, additional, Van Voorhis, Wesley C., additional, McLellan, Jason S., additional, Kleanthous, Harry, additional, Sheahan, Timothy P., additional, Fuller, Deborah H., additional, Villinger, Francois, additional, Bloom, Jesse, additional, Pulendran, Bali, additional, Baric, Ralph, additional, King, Neil, additional, and Veesler, David, additional

Published
2021
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41. Engineered SARS-CoV-2 receptor binding domain improves immunogenicity in mice and elicits protective immunity in hamsters

Author

Dalvie, Neil C., primary, Rodriguez-Aponte, Sergio A., additional, Hartwell, Brittany L., additional, Tostanoski, Lisa H., additional, Biedermann, Andrew M., additional, Crowell, Laura E., additional, Kaur, Kawaljit, additional, Kumru, Ozan, additional, Carter, Lauren, additional, Yu, Jingyou, additional, Chang, Aiquan, additional, McMahan, Katherine, additional, Courant, Thomas, additional, Lebas, Celia, additional, Lemnios, Ashley A., additional, Rodrigues, Kristen A., additional, Silva, Murillo, additional, Johnston, Ryan S., additional, Naranjo, Christopher A., additional, Tracey, Mary Kate, additional, Brady, Joseph R., additional, Whittaker, Charles A., additional, Yun, Dongsoo, additional, Kar, Swagata, additional, Porto, Maciel, additional, Lok, Megan, additional, Andersen, Hanne, additional, Lewis, Mark G., additional, Love, Kerry R., additional, Camp, Danielle L., additional, Silverman, Judith Maxwell, additional, Kleanthous, Harry, additional, Joshi, Sangeeta B., additional, Volkin, David B., additional, Dubois, Patrice M., additional, Collin, Nicolas, additional, King, Neil P., additional, Barouch, Dan H., additional, Irvine, Darrell J., additional, and Love, J. Christopher, additional

Published
2021
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42. Adjuvanting a subunit SARS-CoV-2 nanoparticle vaccine to induce protective immunity in non-human primates

Author

Arunachalam, Prabhu S., primary, Walls, Alexandra C., additional, Golden, Nadia, additional, Atyeo, Caroline, additional, Fischinger, Stephanie, additional, Li, Chunfeng, additional, Aye, Pyone, additional, Navarro, Mary Jane, additional, Lai, Lilin, additional, Edara, Venkata Viswanadh, additional, Röltgen, Katharina, additional, Rogers, Kenneth, additional, Shirreff, Lisa, additional, Ferrell, Douglas E, additional, Wrenn, Samuel, additional, Pettie, Deleah, additional, Kraft, John C., additional, Miranda, Marcos C., additional, Kepl, Elizabeth, additional, Sydeman, Claire, additional, Brunette, Natalie, additional, Murphy, Michael, additional, Fiala, Brooke, additional, Carter, Lauren, additional, White, Alexander G, additional, Trisal, Meera, additional, Hsieh, Ching-Lin, additional, Russell-Lodrigue, Kasi, additional, Monjure, Christopher, additional, Dufour, Jason, additional, Doyle-Meyer, Lara, additional, Bohm, Rudolph B., additional, Maness, Nicholas J., additional, Roy, Chad, additional, Plante, Jessica A., additional, Plante, Kenneth S., additional, Zhu, Alex, additional, Gorman, Matthew J., additional, Shin, Sally, additional, Shen, Xiaoying, additional, Fontenot, Jane, additional, Gupta, Shakti, additional, O’Hagan, Derek T., additional, Most, Robbert Van Der, additional, Rappuoli, Rino, additional, Coffman, Robert L., additional, Novack, David, additional, McLellan, Jason S., additional, Subramaniam, Shankar, additional, Montefiori, David, additional, Boyd, Scott D., additional, Flynn, JoAnne L., additional, Alter, Galit, additional, Villinger, Francois, additional, Kleanthous, Harry, additional, Rappaport, Jay, additional, Suthar, Mehul, additional, King, Neil P., additional, Veesler, David, additional, and Pulendran, Bali, additional

Published
2021
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45. Mapping of a Novel H3-Specific Broadly Neutralizing Monoclonal Antibody Targeting the Hemagglutinin Globular Head Isolated from an Elite Influenza Virus-Immunized Donor Exhibiting Serological Breadth

Author

Qiu, Yu, primary, Stegalkina, Svetlana, additional, Zhang, Jianxin, additional, Boudanova, Ekaterina, additional, Park, Anna, additional, Zhou, Yanfeng, additional, Prabakaran, Ponraj, additional, Pougatcheva, Svetlana, additional, Ustyugova, Irina V., additional, Vogel, Thorsten U., additional, Mundle, Sophia T., additional, Oomen, Ray, additional, Delagrave, Simon, additional, Ross, Ted M., additional, Kleanthous, Harry, additional, and Qiu, Huawei, additional

Published
2020
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48. Corrigendum to “A computationally designed H5 antigen shows immunological breadth of coverage and protects against drifting avian strains” [Vaccine 37 (2019) 2369–2376]

Author

Ross, Ted M., primary, DiNapoli, Joshua, additional, Giel-Moloney, Maryann, additional, Bloom, Chalise E., additional, Bertran, Kateri, additional, Balzli, Charles, additional, Strugnell, Tod, additional, Oomen, Raymond P., additional, Sá e Silva, Mariana, additional, Mebatsion, Teshome, additional, Bublot, Michel, additional, Swayne, David E., additional, and Kleanthous, Harry, additional

Published
2019
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49. Comparison of adjuvants to optimize influenza neutralizing antibody responses

Author

Rudicell, Rebecca S., primary, Garinot, Marie, additional, Kanekiyo, Masaru, additional, Kamp, Heather D., additional, Swanson, Kurt, additional, Chou, Te-hui, additional, Dai, Shujia, additional, Bedel, Olivier, additional, Simard, Daniel, additional, Gillespie, Rebecca A., additional, Yang, Kanwen, additional, Reardon, Michael, additional, Avila, Luis Z., additional, Besev, Magnus, additional, Dhal, Pradeep K., additional, Dharanipragada, Ram, additional, Zheng, Lingyi, additional, Duan, Xiaochu, additional, Dinapoli, Joshua, additional, Vogel, Thorsten U., additional, Kleanthous, Harry, additional, Mascola, John R., additional, Graham, Barney S., additional, Haensler, Jean, additional, Wei, Chih-Jen, additional, and Nabel, Gary J., additional

Published
2019
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