Center for Molecular Medicine Cologne

Schommers, Philipp - assoc. JRG 07 and CAP 26

Laboratory of Antiviral Immunity

Introduction

Interactions between viruses and the immune system of an infected patient have a strong influence on both organisms. After infection, the human immune system aims to improve its ability to detect and combat the respective virus while the pathogen can develop escape mutations that allow him to evade these immune responses. If these mutations also do not alter the ‘viral fitness’ (its ability to replicate and infect more cells), this viral quasispecies will have an evolutionary advantage over the ancestral virus, will finally outnumber him and force the human immune system to adapt its response again.

With the overall aim to improve future antiviral therapies and vaccines, our group aims to i) better understand these host-virus interactions, ii) implement novel techniques to rapidly detect viral escape and iii) develop strategies that hamper viral escape.

Current Projects

One of the most prominent examples of viral escape in the recent years has been SARS-CoV-2 of which new variants have acquired more and more escape mutations that led to a significantly hampered detection and neutralization of the virus by the humoral immune system and monoclonal antibodies.

However, while viruses like SARS-CoV-2 that result in an acute infection only rarely develop escape mutations in most patients, chronically infecting viruses like HIV-1 can develop numerous escape mutations in a single patient over the years which leads to a co-evolution of the immune system and the virus. In very few patients, this co-evolution leads to the development of broadly neutralizing antibodies (bNAbs) that can neutralize up to 100% of worldwide circulating strains.

Antibodies have been ground-breaking in the therapy of autoimmune diseases and cancer and with the recent identification of new highly potent bNAbs, antibodies will also play a key role in future HIV-1 treatment and prevention strategies. HIV-1 reactive bNAbs that target different epitopes on the envelope trimer (Figure 1) have been tested in many clinical studies in recent years, where they demonstrated safe suppression of viremia, a delay of viral rebound after interruption of ART and protection of humans against sensitive strains. The characterization of the interplay between bNAbs and the HIV-1 envelope protein also significantly facilitated the design of novel HIV-1 vaccines of which several candidates are currently already being evaluated in clinical studies.

Figure 1

Current Challenges

As for any drug against HIV-1, viral resistance and escape represent formidable challenges for currently available bNAbs. Effective bNAb therapies and vaccines could be hampered by de novo and pre-existing HIV-1 antibody resistances (HIVAR). RNA viruses, like HIV-1, are characterized by exceptionally high rates of spontaneous mutation.

Especially the HIV-1 envelope protein (HIVenv) can rapidly evade the immune pressure mediated by neutralizing antibodies and clinical trials have shown that such mutations pre-exist in many patients and/or can develop quickly de novo during treatment with bNAbs in humans. Moreover, HIV-1 vaccines that are designed to elicit bNAbs in vaccinees can only be protective against sensitive strains. Thus, rapid testing of patients or even large cohorts for their bNAb sensitivity is crucial for future clinical use of bNAbs of bNAb-inducing vaccines (Figure 2).

Figure 2

Our aims and further perspectives

Our group aims to develop novel methods that will allow the rapid identification of HIV-1 antibody resistances (HIVAR) from replication or translationally competent proviruses in HIV-1 infected individuals (Figure 3). This will help to further characterize and understand HIVAR which will be of upmost importance for future clinical studies. As a result, our work will significantly help to improve future bNAb treatment and prevention strategies as well as HIV-1 vaccines that elicit bNAbs and has the capability to significantly improve the life of HIV-1-infected patients.

Figure 3

Lab Website

For further information please check the Schommers Lab - Laboratory of Antiviral Immunity webpage.

  • Schommers P*, Gruell H*, Abernathy ME*, Tran MK, Dingens AS, Gristick HB, Barnes CO, Schoofs T, Schlotz M, Vanshylla K, Kreer C, Weiland D, Holtick U, Scheid C, Valter MM, van Gils MJ, Sanders RW, Vehreschild JJ, Cornely OA, Lehmann C, Fätkenheuer G, Seaman MS, Bloom JD, Bjorkman PJ, Klein F. Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody. Cell (2020); 180(3):471-489
  • Gruell H, Schommers P. Broadly neutralizing antibodies against HIV-1 and concepts for application. Current Opinion in Virology (2022); 54, 101211.
  • Warnat-Herresthal S*, Schultze H*, Shastry KL*, Manamohan S*, Mukherjee S*, Garg V*, Sarveswara R*, Händler K*, Pickkers P*, Aziz NA*, Ktena S*, Tran F, Bitzer M, Ossowski S, Casadei N, Herr C, Petersheim D, Behrends U, Kern F, Fehlmann T, Schommers P, Lehmann C, Augustin M, Rybniker J, et al. Swarm Learning for decentralized and confidential clinical machine learning. Nature (2021); 594(7862):265-270
  • COVID-19 Host Genetics Initiative. Mapping the human genetic architecture of COVID-19. Nature 2021; 600(7889):472-477
  • Kreer C*, Zehner M*, Weber T, Ercanoglu MS, Gieselmann L, Rohde C, Halwe S, Korenkov M, Schommers P, Vanshylla K, Di Cristanziano V, Janicki H, Brinker R, Ashurov A, Krähling V, Kupke A, Cohen-Dvashi H, Koch M, Eckert JM, Lederer S, Pfeifer N, Wolf T, Vehreschild MJGT, Wendtner C, Diskin R, Gruell H, Becker S, Klein F. Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19 Patients. Cell (2020); 182(4):843-854
  • Gruell H, Vanshylla K, Tober-Lau P, Hillus D, Schommers P, Lehmann C, Kurth F, Sander LE, Klein F. mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omi-cron variant. Nature Medicine (2022); Jan 19:1-4
  • Schoofs T*, Barnes CO*, Suh-Toma N, Golijanin J, Schommers P, Gruell H, West AP Jr, Bach F, Lee YE, Nogueira L, Georgiev IS, Bailer RT, Czartoski J, Mascola JR, Seaman MS, McElrath MJ, Doria-Rose NA, Klein F, Nussenzweig MC, Bjorkman PJ. Broad and Potent Neutralizing Antibodies Recognize the Silent Face of the HIV Envelope. Immunity (2019); 50(6):1513-1529

Overview of publications generated during the current funding period (1/2023-12/2025) with CMMC affiliation

For a complete list of P. Schommers' publications, please visit - pubmed_Schommers

  • Augustin M, Heyn F, Ullrich S, Sandaradura de Silva U, Albert MC, Linne V, Schlotz M, Schommers P, Pracht E, Horn C, Suarez I, Simonis A, Picard LK, Zoufaly A, Wenisch C, Fatkenheuer G, Gruell H, Klein F, Hallek M, Walczak H, Rybniker J, Theobald SJ, and Lehmann C (2023). Immunological fingerprint in coronavirus disease-19 convalescents with and without post-COVID syndrome. Front Med (Lausanne) 10, 1129288. doi:10.3389/fmed.2023.1129288.
     
  • Augustin M, Stecher M, Wustenberg H, Di Cristanziano V, Sandaradura de Silva U, Picard LK, Pracht E, Rauschning D, Gruell H, Klein F, Wenisch C, Hallek M, Schommers P, and Lehmann C (2023). 15-month post-COVID syndrome in outpatients: Attributes, risk factors, outcomes, and vaccination status - longitudinal, observational, case-control study. Front Immunol 14, 1226622. doi:10.3389/fimmu.2023.1226622.
     
  • Kreer C, Lupo C, Ercanoglu MS, Gieselmann L, Spisak N, Grossbach J, Schlotz M, Schommers P, Gruell H, Dold L, Beyer A, Nourmohammad A, Mora T, Walczak AM, and Klein F (2023). Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals. Nat Commun 14, 7137. doi:10.1038/s41467-023-42906-y.
     
  • Malin JJ, Suarez I, Biehl LM, Schommers P, Knops E, Di Cristanziano V, Heger E, Pflieger E, Wyen C, Bettin D, Rybniker J, Fatkenheuer G, and Lehmann C (2023). Immune response to mRNA-based COVID-19 booster vaccination in people living with HIV. HIV Med 24, 785-793. doi:10.1111/hiv.13481.
     
  • Schommers P, Kim DS, Schlotz M, Kreer C, Eggeling R, Hake A, Stecher M, Park J, Radford CE, Dingens AS, Ercanoglu MS, Gruell H, Odidika S, Dahlhaus M, Gieselmann L, Ahmadov E, Lawong RY, Heger E, Knops E, Wyen C, Kummerle T, Romer K, Scholten S, Wolf T, Stephan C, Suarez I, Raju N, Adhikari A, Esser S, Streeck H, Duerr R, Nanfack AJ, Zolla-Pazner S, Geldmacher C, Geisenberger O, Kroidl A, William W, Maganga L, Ntinginya NE, Georgiev IS, Vehreschild JJ, Hoelscher M, Fatkenheuer G, Lavinder JJ, Bloom JD, Seaman MS, Lehmann C, Pfeifer N, Georgiou G, and Klein F (2023). Dynamics and durability of HIV-1 neutralization are determined by viral replication. Nat Med 29, 2763-2774. doi:10.1038/s41591-023-02582-3.
PD Dr. Dr. Philipp Schommers CMMC Cologne
PD Dr. Dr. Philipp Schommers

Clinic I of Internal Medicine

CMMC - PI - assoc. JRG 07 and CAP 26

+49 221 478 89659

+49 221 478 1427272

Clinic I of Internal Medicine

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50931 Cologne

https://www.schommers-lab.cmmc-uni-koeln.de/

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Curriculum Vitae (CV)

Publications on PubMed