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5 results on '"Pardi, Norbert"'

1. Progress in vaccine development for infectious diseases : a Keystone Symposia report

Author

Cable, Jennifer, Graham, Barney S., Koup, Richard A., Seder, Robert A., Karikó, Katalin, Pardi, Norbert, Barouch, Dan H., Sharma, Bhawna, Rauch, Susanne, Nachbagauer, Raffael, Forsell, Mattias N. E., Schotsaert, Michael, Ellebedy, Ali H., Loré, Karin, Irvine, Darrell J., Pilkington, Emily, Tahtinen, Siri, Thompson, Elizabeth A., Feraoun, Yanis, King, Neil P., Saunders, Kevin, Alter, Galit, Moin, Syed M., Sliepen, Kwinten, Karlsson Hedestam, Gunilla B., Wardemann, Hedda, Pulendran, Bali, Doria-Rose, Nicole A., He, Wan-Ting, Juno, Jennifer A., Ataca, Sila, Wheatley, Adam K., McLellan, Jason S., Walker, Laura M., Lederhofer, Julia, Lindesmith, Lisa C., Wille, Holger, Hotez, Peter J., Bekker, Linda-Gail, Cable, Jennifer, Graham, Barney S., Koup, Richard A., Seder, Robert A., Karikó, Katalin, Pardi, Norbert, Barouch, Dan H., Sharma, Bhawna, Rauch, Susanne, Nachbagauer, Raffael, Forsell, Mattias N. E., Schotsaert, Michael, Ellebedy, Ali H., Loré, Karin, Irvine, Darrell J., Pilkington, Emily, Tahtinen, Siri, Thompson, Elizabeth A., Feraoun, Yanis, King, Neil P., Saunders, Kevin, Alter, Galit, Moin, Syed M., Sliepen, Kwinten, Karlsson Hedestam, Gunilla B., Wardemann, Hedda, Pulendran, Bali, Doria-Rose, Nicole A., He, Wan-Ting, Juno, Jennifer A., Ataca, Sila, Wheatley, Adam K., McLellan, Jason S., Walker, Laura M., Lederhofer, Julia, Lindesmith, Lisa C., Wille, Holger, Hotez, Peter J., and Bekker, Linda-Gail

Abstract

The COVID-19 pandemic has taught us many things, among the most important of which is that vaccines are one of the cornerstones of public health that help make modern longevity possible. While several different vaccines have been successful at stemming the morbidity and mortality associated with various infectious diseases, many pathogens/diseases remain recalcitrant to the development of effective vaccination. Recent advances in vaccine technology, immunology, structural biology, and other fields may yet yield insight that will address these diseases; they may also help improve societies' preparedness for future pandemics. On June 1-4, 2022, experts in vaccinology from academia, industry, and government convened for the Keystone symposium "Progress in Vaccine Development for Infectious Diseases" to discuss state-of-the-art technologies, recent advancements in understanding vaccine-mediated immunity, and new aspects of antigen design to aid vaccine effectiveness.

Published
2023
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2. A universal influenza mRNA vaccine candidate boosts T cell responses and reduces zoonotic influenza virus disease in ferrets

Author

van de Ven, Koen, Lanfermeijer, Josien, van Dijken, Harry, Muramatsu, Hiromi, Vilas Boas de Melo, Caroline, Lenz, Stefanie, Peters, Florence, Beattie, Mitchell B, Lin, Paulo J C, Ferreira, José A, van den Brand, Judith, van Baarle, Debbie, Pardi, Norbert, de Jonge, Jørgen, van de Ven, Koen, Lanfermeijer, Josien, van Dijken, Harry, Muramatsu, Hiromi, Vilas Boas de Melo, Caroline, Lenz, Stefanie, Peters, Florence, Beattie, Mitchell B, Lin, Paulo J C, Ferreira, José A, van den Brand, Judith, van Baarle, Debbie, Pardi, Norbert, and de Jonge, Jørgen

Abstract

Universal influenza vaccines should protect against continuously evolving and newly emerging influenza viruses. T cells may be an essential target of such vaccines, as they can clear infected cells through recognition of conserved influenza virus epitopes. We evaluated a novel T cell-inducing nucleoside-modified messenger RNA (mRNA) vaccine that encodes the conserved nucleoprotein, matrix protein 1, and polymerase basic protein 1 of an H1N1 influenza virus. To mimic the human situation, we applied the mRNA vaccine as a prime-boost regimen in naïve ferrets (mimicking young children) and as a booster in influenza-experienced ferrets (mimicking adults). The vaccine induced and boosted broadly reactive T cells in the circulation, bone marrow, and respiratory tract. Booster vaccination enhanced protection against heterosubtypic infection with a potential pandemic H7N9 influenza virus in influenza-experienced ferrets. Our findings show that mRNA vaccines encoding internal influenza virus proteins represent a promising strategy to induce broadly protective T cell immunity against influenza viruses.

Published
2022

3. A universal influenza mRNA vaccine candidate boosts T cell responses and reduces zoonotic influenza virus disease in ferrets

Author

VPDC pathologie, van de Ven, Koen, Lanfermeijer, Josien, van Dijken, Harry, Muramatsu, Hiromi, Vilas Boas de Melo, Caroline, Lenz, Stefanie, Peters, Florence, Beattie, Mitchell B, Lin, Paulo J C, Ferreira, José A, van den Brand, Judith, van Baarle, Debbie, Pardi, Norbert, de Jonge, Jørgen, VPDC pathologie, van de Ven, Koen, Lanfermeijer, Josien, van Dijken, Harry, Muramatsu, Hiromi, Vilas Boas de Melo, Caroline, Lenz, Stefanie, Peters, Florence, Beattie, Mitchell B, Lin, Paulo J C, Ferreira, José A, van den Brand, Judith, van Baarle, Debbie, Pardi, Norbert, and de Jonge, Jørgen

Published
2022

4. A universal influenza mRNA vaccine candidate boosts T cell responses and reduces zoonotic influenza virus disease in ferrets

Author

VPDC pathologie, van de Ven, Koen, Lanfermeijer, Josien, van Dijken, Harry, Muramatsu, Hiromi, Vilas Boas de Melo, Caroline, Lenz, Stefanie, Peters, Florence, Beattie, Mitchell B, Lin, Paulo J C, Ferreira, José A, van den Brand, Judith, van Baarle, Debbie, Pardi, Norbert, de Jonge, Jørgen, VPDC pathologie, van de Ven, Koen, Lanfermeijer, Josien, van Dijken, Harry, Muramatsu, Hiromi, Vilas Boas de Melo, Caroline, Lenz, Stefanie, Peters, Florence, Beattie, Mitchell B, Lin, Paulo J C, Ferreira, José A, van den Brand, Judith, van Baarle, Debbie, Pardi, Norbert, and de Jonge, Jørgen

Published
2022

5. In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels

Author

Rothgangl, Tanja; https://orcid.org/0000-0001-7799-2413, Dennis, Melissa K, Lin, Paulo J C, Oka, Rurika; https://orcid.org/0000-0003-4107-7250, Witzigmann, Dominik; https://orcid.org/0000-0002-8197-8558, Villiger, Lukas, Qi, Weihong, Hruzova, Martina, Kissling, Lucas, Lenggenhager, Daniela, Borrelli, Costanza, Egli, Sabina, Frey, Nina, Bakker, Noëlle, Walker, John A, Kadina, Anastasia P, Victorov, Denis V, Pacesa, Martin; https://orcid.org/0000-0003-1560-5769, Kreutzer, Susanne, Kontarakis, Zacharias; https://orcid.org/0000-0001-8825-8513, Moor, Andreas; https://orcid.org/0000-0001-8715-8449, Jinek, Martin; https://orcid.org/0000-0002-7601-210X, Weissman, Drew, Stoffel, Markus; https://orcid.org/0000-0003-1304-5817, van Boxtel, Ruben; https://orcid.org/0000-0003-1285-2836, Holden, Kevin; https://orcid.org/0000-0002-3091-4124, Pardi, Norbert, Thöny, Beat, Häberle, Johannes, Tam, Ying K, Semple, Sean C, Schwank, Gerald, Rothgangl, Tanja; https://orcid.org/0000-0001-7799-2413, Dennis, Melissa K, Lin, Paulo J C, Oka, Rurika; https://orcid.org/0000-0003-4107-7250, Witzigmann, Dominik; https://orcid.org/0000-0002-8197-8558, Villiger, Lukas, Qi, Weihong, Hruzova, Martina, Kissling, Lucas, Lenggenhager, Daniela, Borrelli, Costanza, Egli, Sabina, Frey, Nina, Bakker, Noëlle, Walker, John A, Kadina, Anastasia P, Victorov, Denis V, Pacesa, Martin; https://orcid.org/0000-0003-1560-5769, Kreutzer, Susanne, Kontarakis, Zacharias; https://orcid.org/0000-0001-8825-8513, Moor, Andreas; https://orcid.org/0000-0001-8715-8449, Jinek, Martin; https://orcid.org/0000-0002-7601-210X, Weissman, Drew, Stoffel, Markus; https://orcid.org/0000-0003-1304-5817, van Boxtel, Ruben; https://orcid.org/0000-0003-1285-2836, Holden, Kevin; https://orcid.org/0000-0002-3091-4124, Pardi, Norbert, Thöny, Beat, Häberle, Johannes, Tam, Ying K, Semple, Sean C, and Schwank, Gerald

Abstract

Most known pathogenic point mutations in humans are C•G to T•A substitutions, which can be directly repaired by adenine base editors (ABEs). In this study, we investigated the efficacy and safety of ABEs in the livers of mice and cynomolgus macaques for the reduction of blood low-density lipoprotein (LDL) levels. Lipid nanoparticle-based delivery of mRNA encoding an ABE and a single-guide RNA targeting PCSK9, a negative regulator of LDL, induced up to 67% editing (on average, 61%) in mice and up to 34% editing (on average, 26%) in macaques. Plasma PCSK9 and LDL levels were stably reduced by 95% and 58% in mice and by 32% and 14% in macaques, respectively. ABE mRNA was cleared rapidly, and no off-target mutations in genomic DNA were found. Re-dosing in macaques did not increase editing, possibly owing to the detected humoral immune response to ABE upon treatment. These findings support further investigation of ABEs to treat patients with monogenic liver diseases.

Published
2021

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