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Abstract

The 2023 annual scientific meeting of the French Society of Toxicologic Pathology (Société Française de Pathologie Toxicologique, SFPT), entitled “mRNA-based technologies: preclinical development and therapeutic applications,” was held in Lyon (France) on May 25 to 26, 2023. The aim of the meeting was to discuss the biology, immunology, and preclinical development of messenger RNA (mRNA)-based vaccines and therapeutics, including immuno-oncology and rare diseases, as well as the regulatory aspect of the COVID-19 vaccines and an overview of the principles and applications of in situ hybridization techniques. This article presents the summary of five lectures along with selected figures, tables, and key literature references on this topic.

Keywords

SFPT annual meeting mRNA regulatory vaccine

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References

Akkaya

Kwak

Pierce

SK.

B cell memory: building two walls of protection against pathogens. Nat Rev Immunol. 2020;20(4):229-238. doi:10.1038/s41577-019-0244-2.

Baden

El Sahly

Essink

, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021;384(5):403-416. doi:10.1056/NEJMoa2035389.

Bange

Han

Wileyto

, et al. CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer. Nat Med. 2021;27(7):1280-1289. doi:10.1038/s41591-021-01386-7.

Bitounis

Jacquinet

Rogers

Amiji

MM.

Strategies to reduce the risks of mRNA drug and vaccine toxicity. Nat Rev Drug Discov. 2024;23(4):281-300. doi:10.1038/s41573-023-00859-3.

Broudic

Amberg

Schaefer

Spirkl

Bernard

Desert

Nonclinical safety evaluation of a novel ionizable lipid for mRNA delivery. Toxicol Appl Pharmacol. 2022;451:116143. doi:10.1016/j.taap.2022.116143.

Broudic

Laurent

Perkov

, et al. Nonclinical safety assessment of an mRNA Covid-19 vaccine candidate following repeated administrations and biodistribution. J Appl Toxicol JAT. 2024;44(3):371-390. doi:10.1002/jat.4548.

Chatterjee

Chattopadhyay

, eds. Nucleic Acid Biology and Its Application in Human Diseases. 1st ed. Singapore: Springer Nature; 2023. doi:10.1007/978-981-19-8520-1.

Chaudhary

Weissman

Whitehead

KA.

mRNA vaccines for infectious diseases: principles, delivery and clinical translation. Nat Rev Drug Discov. 2021;20(11):817-838. doi:10.1038/s41573-021-00283-5.

Cobb

Who discovered messenger RNA?

Curr Biol CB. 2015;25(13):R526-532. doi:10.1016/j.cub.2015.05.032.

10.

Crommelin

DJA

Anchordoquy

Volkin

Jiskoot

Mastrobattista

. Addressing the cold reality of mRNA vaccine stability. J Pharm Sci. 2021;110(3):997-1001. doi:10.1016/j.xphs.2020.12.006.

11.

Destexhe

Prinsen

van Schöll

, et al. Evaluation of C-reactive protein as an inflammatory biomarker in rabbits for vaccine nonclinical safety studies. J Pharmacol Toxicol Methods. 2013;68(3):367-373. doi:10.1016/j.vascn.2013.04.003.

12.

European Medicines Agency (EMA). COVID-19 vaccines: development, evaluation, approval and monitoring. Accessed December 21, 2024. https://www.ema.europa.eu/en/human-regulatory-overview/public-health-threats/coronavirus-disease-covid-19/covid-19-public-health-emergency-international-concern-2020-23/covid-19-vaccines-development-evaluation-approval-monitoring.

13.

European Medicines Agency (EMA). Emergency task force (ETF). Accessed December 21, 2024. https://www.ema.europa.eu/en/committees/working-parties-other-groups/emergency-task-force-etf.

14.

European Medicines Agency (EMA). Guidance for medicine developers and other stakeholders on COVID-19. Accessed December 21, 2024. https://www.ema.europa.eu/en/human-regulatory-overview/public-health-threats/coronavirus-disease-covid-19/covid-19-public-health-emergency-international-concern-2020-23/guidance-medicine-developers-other-stakeholders-covid-19.

15.

European Medicines Agency (EMA). Regulatory requirements for vaccines intended to provide protection against variant strain(s) of SARS-CoV-2: Scientific guideline. Accessed December 21, 2024. https://www.ema.europa.eu/en/regulatory-requirements-vaccines-intended-provide-protection-against-variant-strains-sars-cov-2-scientific-guideline.

16.

Farber

Netea

Radbruch

Rajewsky

Zinkernagel

RM.

Immunological memory: lessons from the past and a look to the future. Nat Rev Immunol. 2016;16(2):124-128. doi:10.1038/nri.2016.13.

17.

Fleming

Krause

Nason

Longini

Henao-Restrepo

AMM

. COVID-19 vaccine trials: The use of active controls and non-inferiority studies. Clin Trials Lond Engl. 2021;18(3):335-342. doi:10.1177/1740774520988244.

18.

Garrido

Curtis

Dennis

, et al. SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques. Sci Immunol. 2021;6(60):eabj3684. doi:10.1126/sciimmunol.abj3684.

19.

Goel

Painter

Apostolidis

, et al. mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern. Science. 2021;374(6572):abm0829. doi:10.1126/science.abm0829.

20.

Hassett

Benenato

Jacquinet

, et al. Optimization of lipid nanoparticles for intramuscular administration of mRNA vaccines. Mol Ther Nucleic Acids. 2019;15:1-11. doi:10.1016/j.omtn.2019.01.013.

21.

Heath

Galiza

Baxter

, et al. Safety and efficacy of NVX-CoV2373 Covid-19 vaccine. N Engl J Med. 2021;385(13):1172-1183. doi:10.1056/NEJMoa2107659.

22.

Hervé

Laupèze

Del Giudice

Didierlaurent

Tavares

Silva

The how’s and what’s of vaccine reactogenicity. NPJ Vaccines. 2019;4:39. doi:10.1038/s41541-019-0132-6.

23.

Khoury

Schlub

Cromer

, et al. Correlates of protection, thresholds of protection, and immunobridging among persons with SARS-CoV-2 infection. Emerg Infect Dis. 2023;29(2):381-388. doi:10.3201/eid2902.221422.

24.

Kis

Kontoravdi

Dey

Shattock

Shah

Rapid development and deployment of high-volume vaccines for pandemic response. J Adv Manuf Process. 2020;2(3):e10060. doi:10.1002/amp2.10060.

25.

Korosec

Farhang-Sardroodi

Dick

, et al. Long-term durability of immune responses to the BNT162b2 and mRNA-1273 vaccines based on dosage, age and sex. Sci Rep. 2022;12(1):21232. doi:10.1038/s41598-022-25134-0.

26.

Malone

Felgner

Verma

IM.

Cationic liposome-mediated RNA transfection. Proc Natl Acad Sci USA. 1989;86(16):6077-6081. doi:10.1073/pnas.86.16.6077.

27.

McMahan

Mercado

, et al. Correlates of protection against SARS-CoV-2 in rhesus macaques. Nature. 2021;590(7847):630-634. doi:10.1038/s41586-020-03041-6.

28.

Milligan

Olstad

Williams

, et al. Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge 1 year later. Sci Transl Med. 2023;15(685):eadd6383. doi:10.1126/scitranslmed.add6383.

29.

Namdari

Jones

Chuang

, et al. Species selection for nonclinical safety assessment of drug candidates: examples of current industry practice. Regul Toxicol Pharmacol RTP. 2021;126:105029. doi:10.1016/j.yrtph.2021.105029.

30.

Parhiz

Atochina-Vasserman

Weissman

mRNA-based therapeutics: looking beyond COVID-19 vaccines. Lancet Lond Engl. 2024;403(10432):1192-1204. doi:10.1016/S0140-6736(23)02444-3.

31.

Plotkin

SA.

Correlates of protection induced by vaccination. Clin Vaccine Immunol CVI. 2010;17(7):1055-1065. doi:10.1128/CVI.00131-10.

32.

Polack

Thomas

Kitchin

, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383(27):2603-2615. doi:10.1056/NEJMoa2034577.

33.

Pooley

Abdool Karim

Combadière

, et al. Durability of vaccine-induced and natural immunity against COVID-19: a narrative review. Infect Dis Ther. 2023;12(2):367-387. doi:10.1007/s40121-022-00753-2.

34.

Qin

Tang

Chen

, et al. mRNA-based therapeutics: powerful and versatile tools to combat diseases. Signal Transduct Target Ther. 2022;7(1):166. doi:10.1038/s41392-022-01007-w.

35.

Rohde

Lindemann

Giovanelli

, et al. Toxicological assessments of a pandemic COVID-19 vaccine-demonstrating the suitability of a platform approach for mRNA vaccines. Vaccines. 2023;11(2):417. doi:10.3390/vaccines11020417.

36.

Sadoff

Gray

Vandebosch

, et al. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. N Engl J Med. 2021;384(23):2187-2201. doi:10.1056/NEJMoa2101544.

37.

Sahin

Karikó

Türeci

Ö.

mRNA-based therapeutics: developing a new class of drugs. Nat Rev Drug Discov. 2014;13(10):759-780. doi:10.1038/nrd4278.

38.

Sahin

Türeci

Ö.

Personalized vaccines for cancer immunotherapy. Science. 2018;359(6382):1355-1360. doi:10.1126/science.aar7112.

39.

Self

Tenforde

Rhoads

, et al. Comparative effectiveness of Moderna, Pfizer-BioNTech, and Janssen (Johnson & Johnson) vaccines in preventing COVID-19 hospitalizations among adults without immunocompromising conditions: United States, March-August 2021. MMWR Morb Mortal Wkly Rep. 2021;70(38):1337-1343. doi:10.15585/mmwr.mm7038e1.

40.

Sheikh-Mohamed

Isho

Chao

GYC

, et al. Systemic and mucosal IgA responses are variably induced in response to SARS-CoV-2 mRNA vaccination and are associated with protection against subsequent infection. Mucosal Immunol. 2022;15(5):799-808. doi:10.1038/s41385-022-00511-0.

41.

Siegrist

C-A.

2: Vaccine immunology. In: Plotkin

Orenstein

Offit

Edwards

, eds. Plotkin’s Vaccines. 7th ed. Amsterdam, The Netherlands: Elsevier; 2018:16.e-34.e7.

42.

Terreri

Piano Mortari

Vinci

, et al. Persistent B cell memory after SARS-CoV-2 vaccination is functional during breakthrough infections. Cell Host Microbe. 2022;30(3):400-408e4. doi:10.1016/j.chom.2022.01.003.

43.

US Food and Drug Administration. Coronavirus disease 2019 (COVID-19). Accessed December 21, 2024. https://www.fda.gov/emergency-preparedness-and-response/public-health-preparedness-and-response/coronavirus-disease-2019-covid-19.

44.

US Food and Drug Administration. Development and licensure of vaccines to prevent COVID-19. Accessed December 21, 2024. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/development-and-licensure-vaccines-prevent-covid-19.

45.

US Food and Drug Administration. Emergency use authorization. Accessed December 21, 2024. https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization.

46.

US Food and Drug Administration. Expedited programs for serious conditions. Drugs and Biologics. Accessed December 21, 2024. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics.

47.

US Food and Drug Administration. Q6B specifications: test procedures and acceptance criteria for biotechnological/biological products. Accessed December 21, 2024. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q6b-specifications-test-procedures-and-acceptance-criteria-biotechnologicalbiological-products.

48.

Voysey

Clemens

SAC

Madhi

, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet Lond Engl. 2021;397(10269):99-111. doi:10.1016/S0140-6736(20)32661-1.

49.

Wei

Pouwels

Stoesser

, et al. Antibody responses and correlates of protection in the general population after two doses of the ChAdOx1 or BNT162b2 vaccines. Nat Med. 2022;28(5):1072-1082. doi:10.1038/s41591-022-01721-6.

50.

Wolff

Malone

Williams

, et al. Direct gene transfer into mouse muscle in vivo. Science. 1990;247(4949Pt1):1465-1468. doi:10.1126/science.1690918.

51.

World Health Organization. Annex 1: WHO guidelines on non clinical evaluation of vaccines. Accessed December 29, 2024. https://www.who.int/publications/m/item/annex1-nonclinical.p31-63.

52.

World Health Organization. Building health systems resilience for universal health coverage and health security during the COVID-19 pandemic and beyond: WHO position paper. Accessed December 21, 2024. https://www.who.int/publications/i/item/WHO-UHL-PHC-SP-2021.01.

53.

World Health Organization. Coronavirus disease (COVID-19). Accessed December 21, 2024. https://www.who.int/emergencies/diseases/novel-coronavirus-2019.

54.

World Health Organization. Coronavirus disease (COVID-19): vaccine research and development. Accessed December 21, 2024. https://www.who.int/news-room/questions-and-answers/item/coronavirus-disease-(covid-19)-vaccine-research-and-development.

55.

World Health Organization. COVAX. Accessed December 21, 2024. https://www.who.int/initiatives/act-accelerator/covax.

56.

World Health Organization. Evaluation of the quality, safety and efficacy of messenger RNA vaccines for the prevention of infectious diseases: regulatory considerations. Accessed December 21, 2024. https://www.who.int/publications/m/item/evaluation-of-the-quality-safety-and-efficacy-of-messenger-rna-vaccines-for-the-prevention-of-infectious-diseases-regulatory-considerations.

57.

World Health Organization. WHO guidelines on non-clinical evaluation of vaccines, Annex 1, TRS No 927. Accessed December 21, 2024. https://www.who.int/publications/m/item/nonclinical-evaluation-of-vaccines-annex-1-trs-no-927.

58.

Yewdell

JW.

Individuals cannot rely on COVID-19 herd immunity: durable immunity to viral disease is limited to viruses with obligate viremic spread. PLoS Pathog. 2021;17(4):e1009509. doi:10.1371/journal.ppat.1009509.

59.

Yuan

Jiao

, et al. The roles of tissue-resident memory T cells in lung diseases. Front Immunol. 2021;12:710375. doi:10.3389/fimmu.2021.710375.

60.

Zhang

Mateus

Coelho

, et al. Humoral and cellular immune memory to four COVID-19 vaccines. Cell. 2022;185(14):2434.e-2451.e17. doi:10.1016/j.cell.2022.05.022.

Proceedings of the 2023 Annual Scientific Meeting of the French Society of Toxicologic Pathology (SFPT) on Preclinical Development and Therapeutic Applications of mRNA-Based Technologies

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