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Dissecting protective immunity to viral vector vaccines for emerging viruses
Summary
Vaccines are one of the most effective public health tools, preventing millions of infections and deaths every year. Recent pandemics, like those caused by Ebola and COVID-19, have highlighted the urgent need for rapid vaccine development and the significant role vaccines can play in controlling outbreaks. mRNA vaccines, in particular, have gained attention due to their success in combating COVID-19, even earning the Nobel Prize in Medicine in 2023 for their groundbreaking technology. However, while mRNA vaccines are a major step forward, it’s important to maintain a diverse range of vaccine technologies, including viral vector vaccines (VVV), to respond to various infectious threats. Combining different vaccine platforms may provide stronger and more lasting immune protection.
Viral vector vaccines have proven their worth in responding quickly to outbreaks, as seen with Ebola virus vaccines. Yet, questions remain about how these vaccines trigger immune responses, particularly in terms of T cell immunity and how the body responds to the viral vector itself. Researchers are also exploring the role of non-neutralizing antibodies in vaccine protection, an area that hasn’t been fully understood. By investigating these mechanisms using data from ongoing vaccine trials, scientists aim to improve our understanding of immune responses and develop vaccines that offer better protection, especially against emerging pathogens and potential future outbreaks, such as "Disease X."
This research will help refine vaccine strategies, ensuring they are both safe and effective for a wide range of diseases. By enhancing our knowledge of how viral vector vaccines work, we will be better prepared to design vaccines that can meet the challenges of future global health threats.
Our Work Packages (WP):
WP1: Analysis of Fc-mediated Humoral Immune Responses
We investigate the non-neutralizing Fc-mediated antibody functions induced by viral vector vaccines (VVV) using systems serology to understand their role in immune protection.
WP2: Investigation of Vector Immunity
We study immune responses against the viral vector backbone to understand how pre-existing or vaccine-induced immunity to the vector affects the overall immune response.
WP3: Comprehensive Analysis of T Cell Immunity
We explore the determinants of T cell immunity induced by VVV to better understand their role in protective immunity and improve vaccine strategies.
Through these work packages, we aim to enhance our understanding of vaccine-induced immunity, which will be essential for developing more effective vaccines for future infectious outbreaks.
Team
Prof. Dr. Marylyn Addo
Principal Investigator
E-mail address:
Phone: +49 (0) 40 7410 - 53786
Research Group Addo
The Institute for Infection Research and Vaccine Development (IIRVD) is based at the University Medical Center Hamburg-Eppendorf (UKE).
Project related publications
Meyer Zu Natrup C, Tscherne A, Dahlke C, …, Addo MM, Becker S, Sutter G, Volz A. Stabilized recombinant SARS-CoV-2 spike antigen enhances vaccine immunogenicity and protective capacity. J Clin Invest. 2022 Dec 15;132(24):e159895. doi: 10.1172/JCI159895
Fathi A, Dahlke C, Krähling V, …, Sutter G, Becker S, Addo MM. Increased neutralization and IgG epitope identification after MVA-MERS-S booster vaccination against Middle East respiratory syndrome. Nat Commun. 2022 Jul 19;13(1):4182. doi: 10.1038/s41467-022-31557-0
Weskamm LM, Fathi A, Raadsen MP, …, Sutter G, Dahlke C, Addo MM. Persistence of MERS-CoV-spike-specific B cells and antibodies after late third immunization with the MVA-MERS-S vaccine. Cell Rep Med. 2022 Jul 19;3(7):100685. doi: 10.1016/j.xcrm.2022.100685
Koch T, Rottstegge M, Ruibal P, …, Günther S, Carroll MW, Addo MM, Muñoz-Fontela C. Ebola Virus Disease Survivors Show More Efficient Antibody Immunity than Vaccinees Despite Similar Levels of Circulating Immunoglobulins. Viruses. 2020 Aug 20;12(9):915. doi:10.3390/v12090915
Koch T, Dahlke C, Fathi A, …, Lohse AW, …, Sutter G, Becker S, Addo MM. Safety and immunogenicity of a modified vaccinia virus Ankara vector vaccine candidate for Middle East respiratory syndrome: an open-label, phase 1 trial. Lancet Infect Dis. 2020 Jul;20(7):827–838. doi: 10.1016/S1473-3099(20)30248-6
Ehrhardt SA#, Zehner M#, Krähling V, …, Addo MM, …, Diskin R, Becker S, Klein F. Polyclonal and convergent antibody response to Ebola virus vaccine rVSV-ZEBOV. Nat Med. 2019;25:1589–1600. doi: 10.1038/s41591-019-0602-4
Fathi A, Dahlke C, Addo MM. Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens. Hum Vaccin Immunother. 2019;15(10):2269–2285. doi: 10.1080/21645515.2019.1649532
Rechtien A, Richert L, Lorenzo H, …, Lohse A, …; VEBCON Consortium; Thiébaut R, Altfeld M, Addo MM. Systems Vaccinology Identifies an Early Innate Immune Signature as a Correlate of Antibody Responses to the Ebola Vaccine rVSV-ZEBOV. Cell Rep. 2017 Aug 29;20(9):2251–2261. doi: 10.1016/j.celrep.2017.08.023
Dahlke C, Kasonta R, Lunemann S, …, Becker S, Addo MM, VEBCON Consortium. Dose-dependent T-cell Dynamics and Cytokine Cascade Following rVSV-ZEBOV Immunization. EBioMedicine. 2017;19:107–118. doi: 10.1016/j.ebiom.2017.03.045 2016
Agnandji ST, Huttner A, Zinser ME, …, Kremsner PG, Addo MM, Siegrist CA. Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe. N Engl J Med. 2016 Apr 28;374(17):1647–1660. doi: 10.1056/NEJMoa1502924
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