The search for vaccines that protect from severe morbidity and mortality as a result of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19) is a race against the clock and the virus. Several vaccine candidates are currently being rolled out in the market. Inactivated virus as well as recombinant protein vaccines can be safe options but may require adjuvants to induce robust immune responses efficiently. We work on novel amphiphilic imidazoquinoline (IMDQ-PEG-CHOL) TLR7/8 adjuvant, consisting of an IMDQ conjugated to the chain end of a cholesterol-poly(ethylene glycol). We study the potential of IMDQ-PEG-CHOL as an adjuvant to achieve protection after single or double immunization with recombinant protein and inactivated vaccines against respiratory viruses, such as SARS-CoV-2 and influenza viruses.
The current COVID-19 pandemic disproportionally affects the elderly and people with comorbidities like obesity and associated type 2 diabetes mellitus. Small animal models are crucial for the successful development and validation of antiviral vaccines, therapies and to study the role that comorbidities have on the outcome of viral infections. Besides vaccine adjuvants, we also study mouse models for advanced age, diabetes and obesity and their outcomes upon SARS-CoV-2 vaccination and infection.
M. White, R. Rosales, S. Yildiz, T. Kehrer, L. Miorin, E. Moreno, S. Jangra, M.B. Uccellini, R. Rathnasinghe, L. Coughlan, et al. Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A. Science, 371 (2021), pp. 926-931
Jangra, S.*; De Vrieze, J.*; Choi, A.*; Rathnasinghe, R.; Laghlali, G.; Uvyn, A.; Van Herck, S.; Nuhn, L.; Deswarte, K.; Zhong, Z.; Sanders, N.; Lienenklaus, S.; David, S.; Strohmeier, S.; Amanat, F.; Krammer, F.; Hammad, H.; Lambrecht, B. N.; Coughlan, L.; García-Sastre, A.; de Geest, B.; Schotsaert, M., Sterilizing Immunity against SARS-CoV-2 Infection in Mice by a SingleShot and Lipid Amphiphile Imidazoquinoline TLR7/8 Agonist-Adjuvanted Recombinant Spike Protein Vaccine. Angewandte Chemie (International ed. in English) 2021.
Jessica Sook Yuin Ho, Bobo Wing-Yee Mok, Laura Campisi, Tristan Jordan, Soner Yildiz, Sreeja Parameswaran, Joseph A. Wayman, Natasha N. Gaudreault, David A. Meekins, Sabarish V. Indran, Igor Morozov, Jessie D. Trujillo, Yesai S. Fstkchyan, Raveen Rathnasinghe, Zeyu Zhu, Simin Zheng, Nan Zhao, Kris White, Helen Ray-Jones, Valeriya Malysheva, Michiel J. Thiecke, Siu-Ying Lau, Honglian Liu, Anna Junxia Zhang, Andrew Chak-Yiu Lee, Wen-Chun Liu, Sonia Jangra, Alba Escalera, Teresa Aydillo, Betsaida Salom Melo, Ernesto Guccione, Robert Sebra, Elaine Shum, Jan Bakker, David A. Kaufman, Andre L. Moreira, Mariano Carossino, Udeni B.R. Balasuriya, Minji Byun, Randy A. Albrecht, Michael Schotsaert, Adolfo Garcia-Sastre, Sumit K. Chanda, Emily R. Miraldi, Anand D. Jeyasekharan, Benjamin R. TenOever, Mikhail Spivakov, Matthew T. Weirauch, Sven Heinz, Honglin Chen, Christopher Benner, Juergen A. Richt, Ivan Marazzi. TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation, Cell, 2021.
Sonia Jangra*, Chengjin Ye*, Raveen Rathnasinghe, Daniel Stadlbauer, Hala Alshammary, Angela A Amoako, Mahmoud H Awawda, Katherine F Beach, Maria C Bermúdez-González, Rachel L Chernet, Lily Q Eaker, Emily D Ferreri, Daniel L Floda, Charles R Gleason, Giulio Kleiner, Denise Jurczyszak, Julia C Matthews, Wanni A Mendez, Lubbertus CF Mulder, Kayla T Russo, Ashley-Beathrese T Salimbangon, Miti Saksena, Amber S Shin, Levy A Sominsky, Komal Srivastava, Florian Krammer, Viviana Simon, Luis Martinez-Sobrido, Adolfo García-Sastre, Michael Schotsaert. SARS-CoV-2 spike E484K mutation reduces antibody neutralization, The Lancet Microbe, 2021.
Sonia Jangra*, Jeffrey J Landers*, Raveen Rathnasinghe, Jessica J O’Konek, Katarzyna W Janczak, Marilia Cascalho, Andrew A Kennedy, Andrew W Tai, James R Baker, Michael Schotsaert, Pamela T Wong. A Combination Adjuvant for the Induction of Potent Antiviral Immune Responses for a Recombinant SARS-CoV-2 Protein Vaccine. Preprint on bioRxiv (https://doi.org/10.1101/2021.02.18.431484), 2021.