PhD Scientific Days 2022

Molecular Sciences IV.

Characterization of the Role of Lymphatic Vessels in mRNA-LNP Vaccine Induced Immune Response

Előadó neve

Dr. Gábor, Kovács

Előadó munkahelye

Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary

Előadó telefonszáma

+36309570117

Előadó e-mail címe

gabor.kovacs1994@gmail.com

Az előadás címe

Characterization of the Role of Lymphatic Vessels in mRNA-LNP Vaccine Induced Immune Response

Szerző(k) neve és munkahelye

Gábor Kovács1, Kornél Molnár1; Éva Kemecsei1, Dániel Szőke1, Raghu P. Kataru2, Babak J. Mehrara2, Norbert Pardi3 and Zoltán Jakus1
1Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary
2 Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
3University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA

Bemutatás módja

Szóbeli

Szekció

Molecular Sciences IV.

Language of the presentation

English

Preferred session

Molecular Sciences

Összefoglaló szövege

Introduction: Lipid nanoparticle-encapsulated mRNA (mRNA-LNP) technology recently gained vast scientific interest, as two vaccines against SARS-CoV-2 (Pfizer-BioNTech, Moderna) are based on this platform. Available data shows the efficacy of these vaccines, yet the specific underlying mechanisms of action are still uncovered. The lymphatic vasculature has important role in multiple immune processes, yet their contribution to the vaccine induced immune response is still unexplored.
Aims: We aimed to characterize the role of lymphatics in nucleoside-modified mRNA-LNP vaccine induced immune response.
Methods: In our experiments we used a transgenic mouse model, in which Diphtheria Toxin (DT) injection induces local lymphatic vessel deletion. The uptake and expression of mRNA-LNPs was characterized by the injection of GFP mRNA-LNP into normal and lymphatic deficient paws and was assessed by stereo microscopy. The humoral immune response was studied by injecting mRNA-LNP encoding influenza hemagglutinin into the lymphatic deficient or control paws, then serum samples were collected, and anti-influenza titer was determined.
Results: The uptake and expression of GFP mRNA-LNPs was observed in the regional lymph node 4h post-injection and peaked at 24h. In the locally lymphatic deficient mice, GFP mRNA-LNP injection into the control paw resulted in GFP expression in the regional lymph node, while injecting it into the lymphatic deficient paw significantly reduced the signal in the regional lymph node. The anti-PR8 HA titer was lower in animals that were vaccinated in the lymphatic deficient paw, compared to animals that were vaccinated in an area with normal lymphatic function.
Conclusions: We present that mRNA-LNPs and its translated products are transported to the regional lymph node in a lymph vessel dependent manner. Our results suggests that damaged lymphatic function weakens humoral response induced by the mRNA- LNP based vaccine. Our results suggests that lymphatic vessels contribute to the vaccine induced immune response.
Funding: NVKP_16-2016-1-0039, K 139165, TKP2021-EGA-29, TKP2021-EGA-24, VEKOP-2.3.2-16-2016-00002, EFOP-3.6.3-VEKOP-16-2017-00009, Scientific and Innovative Research Fund of the Semmelweis University, Szent-Györgyi National Academy of Scientist Education

University and Doctoral School

Semmelweis University, Doctoral School of Molecular Medicine

Supervisor

Zoltán Jakus MD, PhD

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6127

Start

15:15

End

15:30

Authors (legacy)

Gábor Kovács1, Kornél Molnár1; Éva Kemecsei1, Dániel Szőke1, Raghu P. Kataru2, Babak J. Mehrara2, Norbert Pardi3 and Zoltán Jakus1
1Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary
2 Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
3University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA