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Langen Junior Science Award 2022

06 / 2022

Awards Given for Achievements in Research on Vaccine Adjuvants, Measles Infections, and CAR-T Cells

  • Three scientists recognised for innovative research at the Paul-Ehrlich-Institut
  • First place: development of a model system for comparing the modes of action of adjuvants on innate and adaptive immune responses
  • Second place: antiviral treatment of measles as a supplement to the vaccination strategy
  • Third place: improved characterisation of CAR-T cells – new technology established at the Paul-Ehrlich-Institut

From left to right: Professor Klaus Cichutek, Theofilos Filippos Charitidis, Kevin Wittwer, Dr Katrin Bagola (representative for Dr Laura Roßmann), Professor Johannes Löwer, Sandra Schmitt. From left to right: Professor Klaus Cichutek, Theofilos Filippos Charitidis, Kevin Wittwer, Dr Katrin Bagola (representative for Dr Laura Roßmann), Professor Johannes Löwer, Sandra Schmitt. Source: B. Morgenroth/Paul-Ehrlich-Institut

Press Release

The 11th Langen Junior Science Award has been awarded by the Paul-Ehrlich-Institut and the Association for the Promotion of the Langen Science Award. The first prize went to Dr Laura Roßmann (31) for her research on vaccine adjuvants. The second prize went to Kevin Wittwer (28) for his research on the treatment of measles virus infections and the third prize went to Theofilos Filippos Charitidis (29) for his work on CAR-T cells. The awards recognise outstanding research leading to lead author publications in recognised journals.

The prizewinners received their certificates and congratulations on 8 April 2022 from the Chairman of the Association for the Promotion of the Langen Science Prize, Professor Johannes Löwer, Sandra Schmitt, Sparkasse Langen-Seligenstadt, and the President of the Paul-Ehrlich-Institut, Professor Klaus Cichutek. Professor Jan Werner, Mayor of Langen, sent his congratulations on behalf of the city: "We are delighted to support young and talented scientists with the Junior Science Award. We are proud that Langen presents itself as a location for research and teaching, and I would like to thank Sparkasse Langen-Seligenstadt for once again funding this important prize."

The high-quality research at the Paul-Ehrlich-Institut is an integral part of the activities of the Federal Institute for Vaccines and Biomedicines. "Biomedicines are complex and require up-to-date scientific expertise. Our research allows us to develop ideas for new drug concepts and keep abreast of the latest scientific knowledge," explained Cichutek, President of the Institute.

Vaccine adjuvants – comparison of modes of action

The first prize went to Dr Laura Roßmann for her lead author's publication titled "Distinct single-component adjuvants steer human DC-mediated T-cell polarization via Toll-like receptor signaling towards a potent antiviral immune response". In her project, funded by the Federal Ministry of Health (BMG), Dr Roßmann tested ten different adjuvants. Adjuvants are used in vaccines to strengthen the immune response and thus contribute to effective protection against pathogens. A model system of human immune cells isolated from blood donations was established to compare the modes of action of the adjuvants on the innate and adaptive immune responses. The studies were specifically carried out on cultured dendritic cells, which play a central role in the induction of the immune response, and on cocultures of dendritic cells and lymphocytes (white blood cells: B, T and NK cells). The adjuvants stimulated the immune cells to different degrees and had an individual action profile. Understanding the mode of action of adjuvants on cells of the innate and adaptive immune system is helpful in areas such as assessing the breadth of the immune response, the duration of immune protection, and the risk of undesired immune reactions. The research is also important for the regulatory work of the Paul-Ehrlich-Institut and for the development of new vaccines with a view to future pandemics.

Antiviral treatment of measles – a method for supplementing the vaccination strategy

Kevin Wittwer received the second prize for his lead author publication "Small-molecule polymerase inhibitor protects non-human primates from measles and reduces shedding", in which he dealt with the antiviral efficacy of an active substance against measles. The World Health Organisation set a goal of eradicating measles more than 20 years ago. Despite the availability of safe and effective vaccines, this goal has not yet been achieved due to low vaccination rates. Although vaccination is the most important method of eradicating measles viruses, certain groups of people, such as immunocompromised individuals, cannot get vaccinated. Appropriate therapies are therefore urgently needed to prevent what can be a severe disease. ERDRP-0519, the active substance that was studied, inhibits an enzyme (RNA-dependent RNA polymerase) that is important for the reproduction of the measles virus genetic information and thus inhibits virus multiplication. Wittwer carried out the tests on squirrel monkeys. These monkeys develop symptoms during measles infections that are very similar to the symptoms in humans. One prophylactic and two therapeutic treatment options were examined. While the prophylactic treatment completely prevented the symptoms of the disease, the therapeutic treatment, which began either three or seven days after the infection, significantly reduced the progression of the disease and the viral load in blood cells and throat swabs. The study shows that ERDRP-0519 could be used as a supplement to the vaccination strategy and could make an important contribution to the fight against measles.

Better characterisation of CAR-T cells

The third prizewinner is Theofilos Filippos Charitidis for his lead author publication entitled "Monitoring CAR-T cell generation with a CD8-targeted lentiviral vector by single-cell transcriptomics". CAR-T cells are immune system cells (T cells) of cancer patients, which are equipped with a chimeric antigen receptor (CAR) outside the body by means of gene transfer. With the help of a CAR, the immune cells now recognize the cancer cells and kill them. Naturally, the CAR-T cells contain functionally different types of immune cells. Thus, the T cells purified from patient blood contain not only the classical subtypes of regulatory and cytotoxic T cells, but also, depending on the differentiation and activation status, in each case more or less naïve subtypes. Further heterogeneity is mediated by the CAR gene transfer, which does not affect all cells and can also lead to more or less pronounced CAR expression. In his recognised work, Charitidis shows that with single-cell-based transcriptome analysis, heterogeneous drugs such as CAR-T cells can be better characterised than they have been previously. Charitidis created and ran the entire technological process for the first time at the Paul-Ehrlich-Institut, starting with the generation of the CAR-T cells, through the generation of the single-cell RNA library, to the bioinformatic evaluation of the extensive data. In addition to important findings on the methodological and analytical approach, the work also provides initial answers to the question of why some cells within a culture are modified very efficiently by gene transfer, while others are not modified at all.

Original Publications

Rossmann L, Bagola K, Stephen T, Gerards AL, Walber B, Ullrich A, Schülke S, Kamp C, Spreitzer I, Hasan M, David-Watine B, Shorte S, Bastian M, van Zandbergen G (2021): Distinct single-component adjuvants steer human DC-mediated T-cell polarization via Toll-like receptor signaling toward a potent antiviral immune response.
Proc Natl Acad Sci U S A 118: e2103651118.
Online-Abstract


Wittwer K, Anderson DE, Pfeffermann K, Cox RM, Wolf JD, Santibanez S, Mankertz A, Plesker R, Sticher ZM, Kolkykhalov AA, Natchus MG, Pfaller CK, Plemper RK, von Messling V (2021): Small-molecule polymerase inhibitor protects non-human primates from measles and reduces shedding.
Nat Commun 12: 5233.
Text


Charitidis FT, Adabi E, Thalheimer FB, Clarke C, Buchholz CJ (2021): Monitoring CAR T cell generation with a CD8-targeted lentiviral vector by single-cell transcriptomics.
Mol Ther Methods Clin Dev 23: 359-369.
Online-Abstract

Updated: 08.04.2022