Malaria Immunology

The Malaria Immunology group, led by Prof. Carlota Dobaño and Dr. Gemma Moncunill, investigates naturally-acquired and experimentally-induced immunity to infectious diseases of global health relevance. A major focus of the group is malaria and other poverty-related neglected tropical diseases (NTDs), including the impact of co-infections, particularly in vulnerable populations (young children and pregnant women) in low- and middle-income countries.

The Malaria Immunology group performs immuno-epidemiological studies that aim to identify factors affecting disease risk, progression, vaccine immunogenicity and efficacy, and to understand the mechanisms of protective immunity. Knowledge generated is relevant to identify immune correlates of protection, biomarkers of infection and disease progression, and guide the rational development and deployment of vaccines.

To address these research aims, the group employs high throughput multidimensional immune assays, profiling many parameters simultaneously in single biological samples with low volumes (e.g. paediatric populations). Specifically, Prof. Dobaño has pioneered the development of Luminex-based assays to quantify antibodies against large panels of pathogen antigens including the various isotypes and subclasses, and Dr. Moncunill has optimised multi-colour flow cytometer and multiplex cytokine assays, allowing the integration of humoral and cellular immune responses in human cohorts and biomarker studies. The Malaria Immunology group also incorporates multi-omics and data science analytical tools to tackle complex biomedical questions around immunity using systems biology approaches.

These immune profiling approaches, developed mostly as a part of the malaria research work, have also been applied to:

• emergent infectious diseases causing pandemics, including SARS-CoV-2 and COVID-19;
• other infections and vaccines, including viruses or bacteria that trigger other diseases (e.g. cancer); and
• non-communicable diseases (NCDs).

This technical expertise has led to the creation in 2024 of a Core Facility on Immune Response and Biomarkers at ISGlobal as part of CERCA-GYNS platforms, coordinated by Dr. Ruth Aguilar, which offers a wide range of laboratory measurements as services, including Target Olink proteomics, with ISO 9001 certification in process.

The Malaria Immunology group works in close collaboration with the Fundação Manhiça, Centro de Investigação em Saúde de Manhiça (FM-CISM), Mozambique, and other national and international research institutions that conform an extensive network of collaborators from the academia, non-profit organizations and industry.

The group has extensive experience in coordinating multidisciplinary studies and in the leadership of large international research consortia or work packages (EU HEALTH FP6, FP7, H2020, HE, and NIH-NIAID). The Malaria Immunology group is recognized by the Generalitat de Catalunya as an AGAUR consolidated research group (SGR 991) and leads a CIBER group in Spain in infectious diseases of global health relevance (CB21/13/00034).

Specific topics of research interest by the group are:

• Heterogeneity on the quality, function and kinetics of antibody and cellular immune responses in different populations.
• Impact of chronic exposure to infections on the phenotype and function of B and T cell subsets as well as innate cells such as monocytes.
• Impact of disease interventions (e.g. drugs and vaccination) in the acquisition of immunity and approaches to monitoring it.
• Immune responses during pregnancy and neonatal periods, including maternal antibody transfer.
• Immune responses to controlled human malaria infections.
• Immunomodulation and immune deviation by co-infections and exposome.
• Antibody responses to vaccines, particularly malaria (RTS,S/AS0, attenuated sporozoites), COVID-19, influenza and helminths, using systems serology approaches.
• Immune mechanisms and determinants of Long COVID-19.
• Biomarkers of infection, disease progression and pathogenesis

Selected Projects

Malaria

• PI24/00049, Identifying functional antibody and antigen-specific memory B-cell responses associated with RTS,S/AS01E malaria vaccine efficacy and their determinants, Instituto de Salud Carlos III, 2024-2027, IP C. Dobaño.
• PID2022-140479OB-I00, Unravelling the heterogeneity and function of monocytes in vaccination and immunity to malaria (VaMonoS), Ministerio de Ciencia e Innovación, 2023-2026, PI: G. Moncunill.
• 1U01AI165745, Baseline host and environmental factors that impact pre-erythrocytic malaria vaccine (hypo)responsiveness in endemic regions, NIAID-NIH, 2022-2027, PI M. Yazdanbakhsh.
• PI17/02044, Identification of immunological and epidemiological factors associated with the longevity of the efficacy of the RTS,S/AS01E malaria vaccine, Instituto de Salud Carlos III, 2018-2020, IP C. Dobaño.
• R01 AI095789, Understanding RTS,S malaria vaccine-induced protection through integrated analysis of antibody, B cell and T cell immune responses, NIAID NIH, 2012-2020, IP C. Dobaño.
• ImmunoMiPPAD, Impact of antimalarial intermittent preventive treatment in pregnancy in the development of immune responses in Mozambican infants, 2015-2020, IP C Dobaño.

Neglected Tropical Diseases and Coinfections

• 101080784, Innovations for vaccines against helminth infections (WORMVACS2.0). Horizon Europe HEALTH, 2023-2027. PI C. Hokke.
• PI20/00866, Impact of coinfections on the balance of antibody and T helper responses to antigen targets of naturally-acquired and vaccine immunity to major human pathogens, Instituto de Salud Carlos III, 2021-2025, IP C. Dobaño.

COVID-19

• 101046314, Ending COVID-19 variants of concern through cohort studies (END-VOC), Horizon Europe HEALTH, 2023-2025, PI I. Abubakar.
• INFEC23PI07, Biomarkers and underlying immunopathological mechanisms of post COVID-19 condition, CIBERINFEC intramural, 2022-2024, PI G. Moncunill.
• SARS-CoV-2: Knowing transmission. Understanding protection. Fundació Privada Daniel Bravo Andreu, 2020-2023, IP C. Dobaño.
• ANTICOV-IMMUNO, The impact of COVID-19 treatment on the type, strength and duration of antibody and cellular immune responses in SARS-CoV-2 patients in sub-Saharan Africa, UNITAID-DNDi, 2020-2023, IP G. Moncunill.
• ANTICOV-EPI, Factors affecting transmission of SARS-CoV-2 in Households of SARS-CoV-2 patients in Sub-Saharan Africa, UNITAID-DNDi-ITM, 2020-2023, IP G. Moncunill.
• SocAmbCov, Efectos de las condiciones vitales y socioeconómicas y de biomarcadores de contaminantes inmunodepresores en el estado inmunitario basal, la respuesta a la infección por SARS-CoV-2 y la evolución clínica de la COVID-19, Fondos CRUE Santander, 2020-2021, IP M. Porta.
• CV20-204195, Evaluación de la distribución del virus SARS-CoV-2 en pacientes pediátricos mediante un ensayo serológico basado en la técnica Luminex, Junta de Andalucía, 2021, IP M.J. Rodriguez.
• 20877, Identifying protective immunity to SARS-CoV-2 in Health Care Personnel (CoViproteHCt), EIT Health, 2020, IP M. Gerhard.
• TNA2002-08_(COVID-19), Host signatures predicting SARS-CoV-2 antibody responses and their association with protection (SysImmCoV2), TRANSVAC2 European Vaccine Initiative, 2020-2021, IP G. Moncunill.
• SARS-CoV-2 Ivermectin Navarra-ISGlobal Trial (SAINT) proposal to complete the immune-response objectives of the study, Rainwater Foundation, 2020-2021, IP C. Chaccour, C. Dobaño.

Other infections

• 874866, Indo-European Consortium for next generation influenza vaccine innovation (INCENTIVE), H2020 HEALTH EU, 2020-2024, IP C.A. Guzman.
• LaMaratóTV3. Subclinical infections in infants and its impact on health, 2019-2022, PI: E. Kogevinas, Co-PI C. Dobaño.

Selected Collaborations

Malaria

• Centro de Investigaçao em Saúde de Manhiça (CISM), Mozambique.
• Leiden University Medical Center, Leiden, Netherlands: Maria Yazdanbakhsh.
• Radboud University Medical Center, Nijmegen, Netherlands: Benjamin Mordmüller, Mathew McCall.
• IRSS-CRUN, Burkina Faso: Natama Magloire, and ITM Antwerp, Belgium: Anna Rosanas.
• CERMEL, Albert Schweitzer Hospital, Lambaréné, Gabon; Maxime S. Agnandji.
• Burnet Institute, Melbourne, Australia: James Beeson.
• Yale University, USA: John Tsang.
• Walter Reed Army Institute of Research, USA: Evelina Angov, Sheetij Dutta.
• Sanaria Inc, USA: Stephen Hoffman.
• Life Science Research Institute, Dalhousie University, Canada; Tobias Kollmann, Nelly Amenyogbe.

COVID-19

• IDIAP Jordi Gol, Spain, Institut Català de la Salut, Anna Ruiz, Anna Berenguera.
• IrsiCaixa, Spain: Julià Blanco, Marta Masanella.
• IGTP, Spain, Rafael de Cid.
• ITM Antwerp, Belgium: Wim Adriaensen.

Selected Papers

Malaria

• Macià D, Campo JJ, Jairoce C, Mpina M, Sorgho H, Dosoo D, Agnandji ST, Kusi KA, Molinos-Albert LM, Kariuki S, Daubenberger C, Mordmüller B, Moncunill G, Dobaño C. The effect of falciparum exposure and maternal anti-CSP antibodies on responses to RTS,S/AS01_E vaccination in infants and children: an ancillary observational immunological study to a phase 3 randomized clinical trial. Lancet Infect Dis. 2024:S1473-3099(24)00527-9. doi: 10.1016/S1473-3099(24)00527-9. PMID: 39461358. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00527-9/abstract
• Mitchell RA, Macià D, Jairoce C, Mpina M, Naidu A, Chopo-Pizarro A, Vázquez-Santiago M, Campo JJ, Aide P, Aguilar R, Daubenberger C, Dobaño C, Moncunill G. Effect of RTS,S/AS01_E vaccine booster dose on cellular immune responses in African infants and children. NPJ Vaccines. 2024; 9(1):200. doi: 10.1038/s41541-024-00977-y. PMID: 39455625. https://www.nature.com/articles/s41541-024-00977-y
• Jairoce C, Macià D, Torres-Yaguana JP, Mayer L, Vidal M, Santano R, Hurtado-Guerrero R, Reiter K, Narum DL, Lopez-Gutierrez B, Hamerly T, Sacarlal J, Aguilar R, Dinglasan RR, Moncunill G, Izquierdo L, Dobaño C. RTS,S/AS02_A Malaria Vaccine-Induced IgG Responses Equally Recognize Native-Like Fucosylated and Nonfucosylated Plasmodium falciparum Circumsporozoite Proteins. J Infect Dis. 2024;229(3):795-799. doi: 10.1093/infdis/jiad471. PMID: 37889513. https://academic.oup.com/jid/article/229/3/795/7331061
• Beeson JG, Kurtovic L, Valim C, Asante KP, Boyle MJ, Mathanga D, Dobaño C, Moncunill G. The RTS,S malaria vaccine: Current impact and foundation for the future. Sci Transl Med. 2022;14(671):eabo6646. doi: 10.1126/scitranslmed.abo6646. PMID: 36383682. https://www.science.org/doi/10.1126/scitranslmed.abo6646
• Macià D, Campo JJ, Moncunill G, Jairoce C, Nhabomba AJ, Mpina M, Sorgho H, Dosoo D, Traore O, Kusi KA, Williams NA, Oberai A, Randall A, Sanz H, Valim C, Asante KP, Owusu-Agyei S, Tinto H, Agnandji ST, Kariuki S, Gyan B, Daubenberger C, Mordmüller B, Petrone P, Dobaño C. Strong off-target antibody reactivity to malarial antigens induced by RTS,S/AS01_E vaccination is associated with protection. JCI Insight. 2022;7(10):e158030. doi: 10.1172/jci.insight.158030. PMID: 35446785. https://insight.jci.org/articles/view/158030
• Moncunill G, Carnes J, Chad Young W, Carpp L, De Rosa S, Campo JJ, Nhabomba A, Mpina M, Jairoce C, Finak G, Haas P, Muriel C, Van P, Sanz H, Dutta S, Mordmüller B, Agnandji ST, Díez-Padrisa N, Williams NA, Aponte JJ, Valim C, Neafsey DE, Daubenberger C, McElrath MJ, Dobaño C, Stuart K, Gottardo R. Transcriptional correlates of malaria in RTS,S/AS01-vaccinated African children: a matched case-control study. Elife. 2022;11:e70393. doi: 10.7554/eLife.70393. PMID: 35060479. https://elifesciences.org/articles/70393
• Tsang JS, Dobaño C, VanDamme P, Moncunill G, Marchant A, Othman RB, Sadarangani M, Koff WC, Kollmann TR. Improving Vaccine-Induced Immunity: Can Baseline Predict Outcome? Trends Immunol. 2020;41(6):457-465. doi: 10.1016/j.it.2020.04.001. PMID: 32340868. https://www.cell.com/trends/immunology/fulltext/S1471-4906(20)30066-1?sf235299577=1
• Moncunill G, Scholzen A, Mpina M, Nhabomba A, et al, Sauerwein R, Dobaño C. Antigen-stimulated PBMC transcriptional protective signatures for malaria immunization. Sci Transl Med. 2020;12(543):eaay8924. doi: 10.1126/scitranslmed.aay8924. PMID: 32404508. https://www.science.org/doi/10.1126/scitranslmed.aay8924
• Hill DL, Carr EJ, Rutishauser T, Moncunill G, Campo JJ, et al, Dobaño C, Daubenberger C, Linterman MA. Immune system development varies according to age, location, and anemia in African children. Sci Transl Med. 2020;12(529):eaaw9522. doi: 10.1126/scitranslmed.aaw9522. PMID: 32024802. https://www.science.org/doi/10.1126/scitranslmed.aaw9522
• Dobaño C, Nhabomba AJ, Manaca MN, Berthoud T, Aguilar R, et al, Doolan DL, Alonso PL. A Balanced Proinflammatory and Regulatory Cytokine Signature in Young African Children Is Associated With Lower Risk of Clinical Malaria. Clin Infect Dis. 2019;69(5):820-828. doi: 10.1093/cid/ciy934. PMID: 30380038. https://academic.oup.com/cid/article/69/5/820/5151218
• Dobaño C, Sanz H, Sorgho H, Dosoo D, Mpina M, Ubillos I, Aguilar R, et al, Campo JJ, Moncunill G, Gyan B, Valim C, Daubenberger C. Concentration and avidity of antibodies to different circumsporozoite epitopes correlate with RTS,S/AS01_E malaria vaccine efficacy. Nat Commun. 2019;10(1):2174. doi: 10.1038/s41467-019-10195-z. PMID: 31092823. https://www.nature.com/articles/s41467-019-10195-z
• Ubillos I, Ayestaran A, Nhabomba AJ, Dosoo D, Vidal M, Jiménez A, Jairoce C, Sanz H, Aguilar R, Williams NA, Díez-Padrisa N, et al, Moncunill G, Dobaño C. Baseline exposure, antibody subclass, and hepatitis B response differentially affect malaria protective immunity following RTS,S/AS01E vaccination in African children. BMC Med. 2018;16(1):197. doi: 10.1186/s12916-018-1186-4. PMID: 30376866. https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-018-1186-4
• Moncunill G, Mpina M, Nhabomba AJ, Aguilar R, Ayestaran A, Sanz H, Campo JJ, Jairoce C, Barrios D, et al, Dobaño C. Distinct Helper T Cell Type 1 and 2 Responses Associated With Malaria Protection and Risk in RTS,S/AS01E Vaccinees. Clin Infect Dis. 2017;65(5):746-755. doi: 10.1093/cid/cix429. PMID: 28505356. https://academic.oup.com/cid/article/65/5/746/3824758

COVID-19

• Martín Pérez C, Aguilar R, Jiménez A, Salmerón G, Canyelles M, Rubio R, Vidal M, Cuamba I, Barrios D, Díaz N, Santano R, Serra P, Santamaria P, Izquierdo L, Trilla A, Vilella A, Barroso S, Tortajada M, García-Basteiro AL, Moncunill G, Dobaño C. Correlates of protection and determinants of SARS-CoV-2 breakthrough infections 1 year after third dose vaccination. BMC Med. 2024;22(1):103. doi: 10.1186/s12916-024-03304-3. PMID: 38454385. https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-024-03304-3
• Porta M, Pumarega J, Gasull M, Aguilar R, Henríquez-Hernández LA, Basagaña X, Zumbado M, Villar-García J, Rius C, Mehta S, Vidal M, Jimenez A, Campi L, Lop J, Pérez Luzardo OL, Dobaño C, Moncunill G. Individual blood concentrations of persistent organic pollutants and chemical elements, and COVID-19: A prospective cohort study in Barcelona. Environ Res. 2023;223:115419. doi: 10.1016/j.envres.2023.115419. PMID: 36740154. https://www.sciencedirect.com/science/article/pii/S0013935123002116?via%3Dihub
• Dobaño C, Ramírez-Morros A, Alonso S, Rubio R, Ruiz-Olalla G, Vidal-Alaball J, Macià D, Catalina QM, Vidal M, Casanovas AF, Prados de la Torre E, Barrios D, Jiménez A, Zanoncello J, Melero NR, Carolis C, Izquierdo L, Aguilar R, Moncunill G, Ruiz-Comellas A. Sustained seropositivity up to 20.5 months after COVID-19. BMC Med. 2022;20(1):379. doi: 10.1186/s12916-022-02570-3. PMID: 36224590. https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-022-02570-3
• Ortega N, Ribes M, Vidal M, Rubio R, Aguilar R, et al, Moncunill G, Dobaño C. Seven-month kinetics of SARS-CoV-2 antibodies and role of pre-existing antibodies to human coronaviruses. Nat Commun. 2021;12(1):4740. doi: 10.1038/s41467-021-24979-9. PMID: 34362897. https://www.nature.com/articles/s41467-021-24979-9
• Garcia-Basteiro AL, Moncunill G, Tortajada M, Vidal M, et al, Mayor A, Dobaño C. Seroprevalence of antibodies against SARS-CoV-2 among health care workers in a large Spanish reference hospital. Nat Commun. 2020;11(1):3500. doi: 10.1038/s41467-020-17318-x. PMID: 32641730. https://www.nature.com/articles/s41467-020-17318-x

NTDs

• Santano R, Rubio R, Grau-Pujol B, Escola V, Muchisse O, Cuamba I, Vidal M, Ruiz-Olalla G, Aguilar R, Gandasegui J, Demontis M, Jamine JC, Cossa A, Sacoor C, Cano J, Izquierdo L, Chitnis CE, Coppel RL, Chauhan V, Cavanagh D, Dutta S, Angov E, van Lieshout L, Zhan B, Muñoz J, Dobaño C, Moncunill G. Evaluation of antibody serology to determine current helminth and Plasmodium falciparum infections in a co-endemic area in Southern Mozambique. PLoS Negl Trop Dis. 2022;16(6):e0010138. doi: 10.1371/journal.pntd.0010138. PMID: 35727821. https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0010138

Full list of publications

Immune Response and Biomarkers

This core facility provides a service for quantifying a wide range of biomarkers using various platforms, such as ELISA and x-MAP Luminex, as well as targeted proteomics with OLINK (a Certified International Core lab), in a variety of biospecimens. The biomarkers measured are primarily proteins, including antibodies of different isotypes and subclasses against customized panels of antigens, as well as other immune analytes such as cytokines, chemokines, and growth factors. Specific knowledge and capacities offered as added value include extensive expertise and experience with a long track record of the team, the possibility to perform statistical analyses, consulting, training and capacity building (including LMIC laboratory staff).

The Immune Response and Biomarkers website provides access to all relevant service enquiries and pricing.