About 3 million people die each year from vaccine-preventable diseases, mostly concentrated in poor countries. Developing vaccines for poor countries is the main mission of this research group. More stable and needle-free, self-administrable, oral and intranasal vaccines would help, not only to increase the vaccine coverage, but also to decrease the infections associated with bad clinical practices during the administration of injectables. The group have been working on the re-designing of the hepatitis B vaccine with the aim of helping WHO achieve one of the 2030 elimination targets. 

To achieve its Mission, this research group has established the following objectives:

-    To design a therapeutic hepatitis B vaccine

-    To develop adjuvants for intranasal vaccines to protect against respiratory infections including the new SARS-COV-2 

-    To design vaccine adjuvants for the oral route of administration.

-    To design adjuvants for the more stable genetic (DNA and RNA) vaccines. 



The nanotechnology is the facilitating tool to obtain ‘pathogen-like’ particulate adjuvants. Our research group assumed that combining on same nanoparticle several immunopotentiators, the resultant adjuvant would have predictable immunomodulatory properties for an intended vaccine. Therefore, the main objective has been to design and develop the methods for obtaining polymeric nanoparticles with pathogen-mimicking characteristics.
 

Techniques and expertise 
Preparation methods to obtain antigen and/or immunopotentiator loaded polymeric nanoparticles; Physicochemical characterization of the nanoparticles using standardized methods and protocols; Interaction studies of the nanoparticles with biological membranes and with immune cells; immunotoxicological tests with nanoparticles; immunization studies and evaluation of the cellular and humoral immune response. 
 

Keywords:

Nanotechnology;
Chitosan,
Glucan,
Hepatitis B;
Vaccine Adjuvants

Research Lines:

1 - Polysaccharide and Polyester based particulate vaccine adjuvants

2 – Immunotoxicologycal non-desired aspects of the nanoparticles (polymeric nanoparticles as drug delivery systems and environmental particles)

Ongoing Research Projects

1.    “Hepatitis B Therapeutic Vaccine: Production of glucan-based particles towards selective delivery hepatitis B antigens to immune cells to induce antiviral activity”.  POCI-01-0145-FEDER-030331 (2018-2021) Participation: Principal Investigator

2.    “InPaCTus” Produtos e Tecnologias Inovadoras a partir do Eucalipto, Centro de Excelência, PORTUGAL2020, POCI-01-0247-FEDER-021874; projeto co-promoção "The Navigator Company"-RAIZ-Univ. Coimbra-Univ. Aveiro (subproject “Extracts of defined value from forest biomass”) (2017-2020), Participation: Collaborator 

3.     “Skin allergens: molecules with an improbable therapeutic application for Alzheimer´s disease” POCI-01-0145-FEDER-029369, (2018-2021) Participation: Collaborator 

4.    Giardia Lamblia Extracellular Vesicles in host cell immunomodulation: potential therapeutic application of Giardia EVs in intestinal inflammation. PTDC/SAU-PAR/31506/2017 (2018-2021) Participation: Collaborator

5.    "Impact of the action of natural products on human innate immune and tumor cells." CAPES-PRINT-UNESP AGREEMENT - NOTICE 02/2019. International Research Neworks with UC participation Participation: Collaborator


External Collaborations 

Gerrit Borchard - Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland

Claudia Som - Laboratory for Technology and Society, Empa Swiss Laboratories for Materials Science and Technology, St. Gallen, Switzerland

Peter Wick - Laboratory for Particles-Biology Interactions, Empa Swiss Laboratories for Materials Science and Technology, St. Gallen, Switzerland

Herman F. Staats - Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA

André Boonstra - Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, the Netherlands

Ed Lavelle - Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin 2, Ireland.

1- Chitosan Nanoparticles: Shedding Light on Immunotoxicity and Hemocompatibility. Jesus S, Marques AP, Duarte A, Soares E, Costa JP, Colaço M, Schmutz M, Som C, Borchard G, Wick P, Borges O. Front Bioeng Biotechnol. 2020;8:100. Published 2020 Feb 21. doi:10.3389/fbioe.2020.00100

2-Safe-by-Design of Glucan Nanoparticles: Size Matters When Assessing the Immunotoxicity. Colaço M, Marques AP, Jesus S, Duarte A, Borges O. Chem Res Toxicol. 2020;10.1021/acs.chemrestox.9b00467. doi:10.1021/acs.chemrestox.9b00467

3-Glucan particles are a powerful adjuvante for the HBsAg inducing na antiviral cytokine profile;  Edna Soares, Groothuismink, Anthonie; Boonstra, Andre and Borges, Olga Mol Pharm. 2019 May 6;16(5):1971-1981. doi: 10.1021/acs.molpharmaceut.8b01322.

4-Polymeric nanoengineered HBsAg DNA vaccine designed in combination with β glucan.; Soares E, Cordeiro R, Faneca H, Borges O.;Int J Biol Macromol. 2019 Feb 1; 122:930-939. doi: 10.1016/j.ijbiomac.2018.11.024. 

5- Exosomes as adjuvants for the recombinant hepatitis B antigen: First report; Jesus S; Soares E; Cruz M; Borges O; European Journal of Pharmaceutics and Biopharmaceutics (2018) 133: 1-11. doi: 10.1016/j.ejpb.2018.09.029.

6-Mechanistic study of the adjuvant effect of chitosan-aluminum nanoparticles Lebre F; Pedroso de Lima M; Lavelle E; Borges O; International Journal of Pharmaceutics (2018) 552(1-2):7-15; doi: 10.1016/j.ijpharm.2018.09.044.

7-Oral hepatitis B vaccine: chitosan or glucan based delivery systems for efficient HBsAg immunization following subcutaneous priming; Soares E, Jesus S, Borges O.; Int J Pharm. 2018; 15; 535(1-2): 261-271; doi: 10.1016/j.ijpharm.2017.11.009.

8-Intranasal administration of novel chitosan nanoparticles/DNA complexes induces antibody response to hepatitis B surface antigen in mice; Lebre F, Borchard G, H. Faneca, de Lima MC, Borges O. Molecular Pharmaceutics 2016, 13(2), 472-482 doi: 10.1021/acs.molpharmaceut.5b00707. 

9-Effect of particulate adjuvant on the anthrax protective antigen dose required for effective nasal vaccination.
Bento D, Staats HF, Borges O.; Vaccine. 2015 Jul 17;33(31):3609-13. doi: 10.1016/j.vaccine.2015.06.037. Epub 2015 Jun 15.
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10-Uptake studies in rat Peyer’s patches, cytotoxicity and release studies of alginate coated chitosan nanoparticles for mucosal vaccination. Olga Borges, Anabela Cordeiro-da-Silva, Stefan G. Romeijn, Maryam Amidi, Adriano de Sousa, Gerrit Borchard and Hans E. JungingerJournal of Controlled Release 111 (2006) 348-358. DOI:10.1016/j.jconrel.2006.06.011