Human Immunobiology and Pathogenesis Laboratory

Using the ultimate disease model: the Human, the Human Immunobiology and Pathogenesis Lab aims at understanding tissue- and cell-specific factors controlling the induction of protective versus pathogenic immunity throughout human life, from in-uterus to the elderly.

Studies in inbred animals have proven indispensable for unravelling the molecular underpinnings of the immune system. We have made less progress, however, in understanding the workings of the human immune system. All too often, animal models fail to faithfully recapitulate all the facets of human disease, and therapies that work well in preclinical models fail to show efficacy in human trials.

A particular area of interest consists in determining the key factors driving the sex-bias in immune responses. Central to our research is the molecular access to human tissues and a mechanism-driven development of biologicals at the interface of immunology, clinical research and biotechnology. We have partnership agreements with 8 other institutions, including research centers, as well as 5 hospitals and Gilead and Pfizer Pharma support. In the last 5 years, our group has secured national and european funding and high impact publications.

Graphical Abstract

Featured Projects

I - Reprogramming inflammatory-follicular T cells (Tfhi): from the clinic to precision immunotherapies.
- I.1)To identify the tissue-specific mechanisms underpinning joint destruction in rheumatoid arthritis patients
- I.2)Amaral-Silva D, Gonçalves R, Torrão RC, Torres R, Pimentel-Santos F, Mourão AF, Costa M, Falcão S, Araújo MP, Gonçalves MJ, Lopes C, Neto A, Marona J, Costa T, Costa W, Branco JC, Helena Soares . Direct tissue sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patients. Communications Biology 2021 in press
- I.6) Daniela Amaral-Silva, Rute Gonçalves e Rita Torrão.
II - Uncovering HIV-1 follicular reservoirs and viral evolution.
- I.1)To decipher how HIV-1 establishes follicular reservoirs and how HIV-1 genetic evolution conditions its pathogenicity.
- II.2)
  - i)Santos-Pereira A, Triunfante V, Araújo PMM, Martins J, Soares H, Poveda E, Souto B, Osório NS. Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Int. J. Mol. Sci. 2021. 22(10), 5304
  - ii)Sebastião CS*, Neto Z, de Jesus, Mirandela M, Jandondo D, Couto-Fernandéz JC, Tanuri A, Morais J, Brito M (2019) Genetic diversity and drug resistance of HIV-1 among infected pregnant women diagnosed in Luanda, Angola. PlOs One 14(11):e0225251
  - iii)Alencar D, Gonçalves J, Cerqueira AS, Soares H , Petronilho A . Development of Triazoles based on AZT and their Anti-Viral Activity Against HIV-1. BioRxiv 2019
  - iv) Silva JG, Martins NP, Henriques R, Soares H . HIV-1 Nef Impairs the Formation of Calcium Membrane Territories Controlling the Signaling Nanoarchitecture at the Immunological Synapse. J. Immunol. 2016. 197: 4042
- II.6) Raquel Sousa, Sofia Cerqueira, Juliana Gonçalves, Cruz Sebastião
III - Tracking COVID-19 disease and vaccination in HCW, and in pregnant and lactating women
- III.1) Identify the key immunological players (cellular and serological) involved in the response to COVID-19 disease and vaccination in health care workers (HCW), but also in pregnant and lactating women that were excluded from vaccine clinical trials. In these latter population groups, the degree of immune protection transferred to the suckling infant in uterus and/or through breastfeeding will also be evaluated.
- III.2)
  - i) Alenquer M, Ferreira F, Lousa D, Valério M, Medina-Lopes M, Bergman M-L, Gonçalves J, Demengeot J, Leite RB, Lilue J, Ning Z, Penha-Gonçalves C, Soares H, Soares CM, Amorim MJ. Amino acids 484 and 494 of SARS-CoV-2 spike are hotspots of immune evasion affecting antibody but not ACE2 binding. PLOS Pathogens 2021. 17(8): e1009772.
  - ii) Gonçalves J, Juliano AM, Charepe N, Alenquer M, Athayde D, Ferreira F, Archer M, Amorim MJ, Serrano F, Soares H . Non-neutralizing secretory IgA and T cells targeting SARS-CoV-2 spike protein are transferred to the breastmilk upon BNT162b2 vaccination. MedRxiv 2021 https://doi.org/10.1101/2021.05.03.21256416
  - iii)Gonçalves J, Sousa RL, Jacinto MJ, Amaral-Silva D, Paula F, Sousa R, Zahedi S, Carvalho J, Cabral MG, Costa M, Branco JC, Canhão H, Alves JD, Rodrigues A, Soares H . Evaluating SARS-CoV-2 Seroconversion Following Relieve of Confinement Measures. Front Med 2020. https://doi.org/10.3389/fmed.2020.603996
  - III.5) Co-organizer and scientific content curator of the National Campaign for Vaccine Awareness Campaign “Conversation with Scientists: Decades of Science for Days of Vaccination” (link: https://www.cienciaviva.pt/divulgacao-cientifica/vacinas-covid19#df68-5c18-fa9d-4efa)
  - III.6) Juliana Gonçalves, Magda Melro, Margarida Juliano

Projects

Tackling infection through modulation of the hormonal-immune axis, European Society for Clinical Microbiology and Infectious Diseases (ESCMID). PI: Juliana Gonçalves.
Reprogramming inflammatory-follicular T cells (Tfhi): from the clinic to precision immunotherapies. Funded by FCT (PTDC/MEC-REU/29520/2017);
Uncovering HIV-1 follicular reservoirs and viral evolution. Funded by: European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Gilead Génese (PGG 009/2016 and PGG 009/2017) and NOVASaúde;
Sex bias in immune responses;
Tracking COVID-19 disease and vaccination in HCW, and in pregnant and lactating women.

Publications

Juliana Goncalves, Magda Melro, Marta Alenquer, Catarina Araujo, Julia Castro-Neves, Nadia Charepe, Fatima Serrano, Carlos Pontinha, Maria Joao Amorim, Helena Soares. Balance between maternal antiviral response and placental transfer of protection in gestational SARS-CoV-2 infection. & medRxiv
Clerbaux L-A, Mayasich SA, Muñoz A, Soares H, Petrillo M, Albertini MC, Lanthier N, Grenga L, Amorim M-J. Gut as an Alternative Entry Route for SARS-CoV-2: Current Evidence and Uncertainties of Productive Enteric Infection in COVID-19. Journal of Clinical Medicine. 2022; 11(19):5691. https://doi.org/10.3390/jcm11195691
Clerbaux L-A, Albertini MC, Amigó N, Beronius A, Bezemer GFG, Coecke S, Daskalopoulos EP, del Giudice G, Greco D, Grenga L, Mantovani A, Muñoz A, Omeragic E, Parissis N, Petrillo M, Saarimäki LA, Soares H, Sullivan K, Landesmann B. Factors Modulating COVID-19: A Mechanistic Understanding Based on the Adverse Outcome Pathway Framework. Journal of Clinical Medicine. 2022; 11(15):4464. https://doi.org/10.3390/jcm11154464; Preprint.
Francesca P, Mauro P, Clerbaux LA, Leoni G, Ponti J, Bogni A, Brogna C, Cristoni S, Sanges R, Mendoza-de Gyves E, Fabbri M, Querci M, Soares H, Munoz Pineiro A, Whelan M, Van de Eede G. Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation: possible implications for SARS-CoV-2 impact on brain development. Reprod Toxicol. 2022 May 4;111:34–48. doi: 10.1016/j.reprotox.2022.04.011. Epub ahead of print. PMID: 35525527; PMCID: PMC9068247.
Pistollato Francesca, Petrillo Mauro, Laure-Alix Clerbaux, Gabriele Leoni, Jessica Ponti, Alessia Bogni, Carlo Brogna, Simone Cristoni, Remo Sanges, Emilio Mendoza-de Gyves, Marco Fabbri, Maddalena Querci, Helena Soares, Amalia Munoz Pineiro, Maurice Whelan, Guy Van de Eede, Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation: possible implications for SARS-CoV-2 impact on brain development, Reproductive Toxicology, 2022, https://doi.org/10.1016/j.reprotox.2022.04.011
Gonçalves J, Juliano AM, Charepe N, Alenquer M, Athayde D, Ferreira F, Archer M, Amorim MJ, Serrano F, Soares H. Secretory IgA and T cells targeting SARS-CoV-2 spike protein are transferred to the breastmilk upon mRNA vaccination. Cell Rep Med. 2021 Dec 2:100468. doi: 10.1016/j.xcrm.2021.100468. Epub ahead of print. PMID: 34873588; PMCID: PMC8636305.
Amaral-Silva D., Gonçalves R. Torrão R.C., Torres R., Falcão S., Gonçalves M.J., Araújo M.P., Martins M.J., Lopes C., Neto A., Marona S., Costa T., Castelão W., Silva A.B., Silva I., Lourenço M.H., Mateus M., Gonçalves N.P., Manica S., Costa M., Pimentel-Santos F.M., Mourão A.F., Branco J.C., Soares H. Direct tissue-sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patients. Commun Biol 4, 1135 (2021). https://doi.org/10.1038/s42003-021-02659-0
Alenquer M, Ferreira F, Lousa D, Valério M, Medina-Lopes M, Bergman ML, Gonçalves J, Demengeot J, Leite RB, Lilue J, Ning Z, Penha-Gonçalves C, Soares H, Soares CM, Amorim MJ. Signatures in SARS-CoV-2 spike protein conferring escape to neutralizing antibodies. PLoS Pathog. 2021 Aug 5;17(8):e1009772. doi: 10.1371/journal.ppat.1009772. PMID: 34352039
Santos-Pereira A, Triunfante V, Araújo PMM, Martins J, Soares H, Poveda E, Souto B, Osório NS. Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Int. J. Mol. Sci. 2021. 22(10), 5304
Gonçalves J, Juliano AM, Charepe N, Alenquer M, Athayde D, Ferreira F, Archer M, Amorim MJ, Serrano F, Soares H . Non-neutralizing secretory IgA and T cells targeting SARS-CoV-2 spike protein are transferred to the breastmilk upon BNT162b2 vaccination. MedRxiv 2021 https://doi2021.05.03.21256416.org/10.1101/
Juliana Gonçalves, Rita L. Sousa, Maria J. Jacinto, Daniela A. Silva, Filipe Paula, Rute Sousa, Sara Zahedi, Joana Carvalho, M. Guadalupe Cabral, Manuela Costa, Jaime C. Branco, Helena Canhão, José D. Alves, Ana M. Rodrigues and Helena Soares (2020) Evaluating SARS-CoV-2 Seroconversion Following Relieve of Confinement Measures. Frontiers in Medicine (7) doi: 10.3389/fmed.2020.603996
Silva Z, Ferro T, Almeida D, Soares H, Ferreira JA, Deschepper FM, Hensbergen PJ, Pirro M, van Vliet SJ, Springer S, Paula A. Videira. MHC class I stability is modulated by cell surface sialylation in human dendritic cells. Pharmaceuticals. 2020. 12(3):E249
Sebastião CS#, Neto Z, de Jesus CS, Mirandela M, Jandondo D, Couto-Fernandéz JC, Tanuri A, Morais J, Brito M. PlOs One. 2019. 14(11)e0225251 #paper with laboratory affiliation
Alencar D, Gonçalves J, Cerqueira AS, Soares H , Petronilho A . Development of Triazoles based on AZT and their Anti-Viral Activity Against HIV-1. BioRxiv 2019
Silva JG, Martins NP, Henriques R, Soares H . HIV-1 Nef Impairs the Formation of Calcium Membrane Territories Controlling the Signaling Nanoarchitecture at the Immunological Synapse. J. Immunol. 2016. 197: 4042 Highlighted in J Immunol November 15, 2016, 197 (10) 3749-3750
Soares H . HIV-1 intersection with CD4 T cell vesicle exocytosis: intercellular communication goes viral. Frontiers in Immunology. 2014. 5:454

Prizes and Awards

2021-2023 Best European Campaign Award, granted by International Union of Immunological Societies (IUIS) and European Federation of Immunological Societies (EFIS). Roles: Member of the core organizing team and scientific curator.
(2022) Portuguese Society of Immunology (SPI) Travel Award to Daniela Amaral-Silva
(2022) Nova Health Chronic Disease and Infection Best Poster Prize to Júlia Castro-Neves
(since 2021) Secretary-General on the Board of Direction of Portuguese Society for Immunology
(since 2021) European Commission expert and collaborator of JCR Ispra (Italy) on the project “Modelling the pathogenesis of Covid-19, based on the Adverse Outcome Pathway paradigm” coordinated by. Clemens Wittwehr and Brigitte Landesmann.
(2021-27) CEEC contract ref. CEECIND/01049/2020 FCT PI Salary Contract
(2020) Scientific coordinator of COVID-19 serological taskforce at CEDOC|NMS
(since 2020) Institutional representative of Serology4Covid Consortium
(2014-2019) IF contract, FCT PI Salary Contract
(2008-2019) European Molecular Biology Organization (EMBO) Long-term fellowship

Open Positions

International selection competition procedure for the hiring of a PhD holder (Notice no. 11958/2022) @Helena Soares Lab

Investigator

Pursuant to the provisions of article 11, paragraph 2, of Decree-Law no. 57/2016, of August 29, it becomes public that by Dean’s decree of May 17, 2022, the opening of an international selection competition procedure was authorized for the completion of a PhD holder job vacancy for the exercise of scientific research activities in the scope of the project LISBOA-01-0145-FEDER-029520, funding granted by the Programa Operacional Regional de Lisboa supported by the FEDER and by national funds, through the Fundação para a Ciência e Tecnologia, I.P. (FCT, I.P), under an uncertain fixed-term employment contract under the Labor Code in the Faculdade de Ciências Médicas|NOVA Medical School from Universidade NOVA de Lisboa.

Application deadline: June 29, 2022 (until 30/06/2022 00:00)

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Media

Joint Effort Leads To Breakthrough In Prediction Of Sars-Cov-2 Mutations

A joint effort between 3 Portuguese institutes, including CEDOC-NMS School, warns of 2 mutations in SARSCoV2 spike protein that could elude the immune system.

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New research led by Helena Soares studies COVID-19 immunity in breast milk

A brand new study regarding the transference of COVID-19 immunity from breast milk to newborns was just published in Cell Reports Medicine, led by Helena Soares lab, Immunobiology and Pathogenesis, along with partners in ITQB NOVA and IGC.

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NMS Research with full representation at Ciência 2022

NOVA Medical School will be present at Ciência 2022, the largest meeting of Science and Technology in Portugal, with full representation of its research with its four Research Units and three Associate Laboratories, during for the entire duration of the event at Centro de Congressos de Lisboa.

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