- Diagnostics: I developed a diagnostic test that distinguishes antibody responses from Dengvaxia vaccination versus natural dengue infection. This revealed that dengue-naive individuals vaccinated with Dengvaxia had an increased risk of severe disease. The findings led to changes in the vaccine label and WHO usage recommendations, ultimately saving countless lives.
- E. J. M. Nascimento et al., Development of an anti-dengue NS1 IgG ELISA to evaluate exposure to dengue virus. J Virol Methods 257, 48–57 (2018).
- E. J. M. Nascimento et al., Development of antibody biomarkers of long term and recent dengue virus infections. J Virol Methods 257, 62–68 (2018).
- Vaccine adjuvant: I co-developed a molecular adjuvant using LAMP technology to enhance MHC class II presentation and CD4/CD8 T-cell responses. This innovation led to 40+ publications, multiple patents, and a $300M licensing deal. LAMP has been applied to vaccines against HIV, dengue, Ebola, cancer, and allergies. Two therapeutic vaccines using this technology are in clinical trials: one targets cytomegalovirus for glioblastoma, and the other targets Merkel cell polyomavirus for Merkel cell carcinoma.
- E. T. Marques, Jr. et al., HIV-1 p55Gag encoded in the lysosome-associated membrane protein-1 as a DNA plasmid vaccine chimera is highly expressed, traffics to the major histocompatibility class II compartment, and elicits enhanced immune responses. J Biol Chem 278, 37926–37936 (2003).
- L. B. Arruda et al., Dendritic cell-lysosomal-associated membrane protein (LAMP) and LAMP-1-HIV-1 Gag chimeras have distinct cellular trafficking pathways and prime T and B cell responses to a diverse repertoire of epitopes. Journal of Immunology 177, 2265–2275 (2006).
- Epitope-Based Vaccine Design: Vaccine development for some pathogens fails because they divert immune responses toward irrelevant targets. To address this, I developed a “forward and backward” approach combining computational tools and high-throughput assays to identify T-cell epitopes in clinical samples and HLA-transgenic models. Using LAMP technology, we engineered a dengue epitope-based vaccine incorporating epitope clusters that elicit CD4/CD8 responses in 95% of the HLA alleles in the population, enhancing targeted and effective immune responses.
- E. J. Nascimento et al., Identification of conserved and HLA promiscuous DENV3 T-cell epitopes. PLoS Negl Trop Dis 7, e2497 (2013).
- U. M. Braga-Neto, E. T. Marques, Jr., From functional genomics to functional immunomics: new challenges, old problems, big rewards. PLoS Comput Biol 2, e81 (2006).
- Congenital Zika Syndrome: In 2003, I launched a hospital-based study in Recife, Brazil, on dengue and other arboviral diseases. In 2015, we identified the first Zika cases and detected the virus in cerebrospinal fluid of adults with demyelinating diseases, preceding the microcephaly outbreak. Later we confirmed the link between Zika and congenital disease, estimated risks for WHO, and developed an anti-Zika NS1 IgG3 assay to identify women at risk. We also found that high dengue antibody levels reduced Zika infection risk.
- T. Magalhaes et al., Zika virus displacement by a chikungunya outbreak in Recife, Brazil. PLoS Negl Trop Dis 11, e0006055 (2017).
- T. Jaenisch et al., Risk of microcephaly after Zika virus infection in Brazil, 2015 to 2016. Bull World Health Organ 95, 191–198 (2017).
- Zika immunopathology: Zika infection during pregnancy increases the risk of microcephaly and other congenital abnormalities, though only 3–7% of infections result in Congenital Zika Syndrome (CZS), depending on gestational age. Socioeconomic and environmental factors may also influence risk. We investigated CZS pathogenesis and were first to detect Zika virus and IgM in cerebrospinal fluid from initial 2015 cases. We also demonstrated that anti-dengue antibodies facilitate Zika infection of immune cells in blood and in ex vivo skin explant models. The identification of these mechanisms helps develop vaccines and other measures to prevent Zika infection.
- M. T. Cordeiro, L. J. Pena, C. A. Brito, L. H. Gil, E. T. Marques, Positive IgM for Zika virus in the cerebrospinal fluid of 30 neonates with microcephaly in Brazil. Lancet 387, 1811–1812 (2016).
- P. M. S. Castanha et al., Dengue Virus-Specific Antibodies Enhance Brazilian Zika Virus Infection. J Infect Dis 215, 781–785 (2017).
September, 1993 |Universidade Federal de Pernambuco, Recife, Brazil | MD
May, 1999 | The Johns Hopkins University School of Medicine | PhD
IDM 2103 Host Response to Microbial Infection
IDM 2037 Vector-Borne Infectious Diseases: Research and Practice
Priscila M. S. Castanha, Dylan J. Tuttle Georgios D. Kitsios, Jana L. Jacobs, Ulisses Braga-Neto, Matthew Duespohl, Sanjay Rathod, Michelle M. Marti, Sarah Wheeler,8, Asma Naqvi, Brittany Staines, John Mellors, Alison Morris, Bryan J. McVerry, Faraaz Shah, Caitlin Schaefer, Bernard J. C. Macatangay, Barbara Methe, Christian A. Fernandez, Simon M. Barratt-Boyes, Donald Burke,Ernesto T. A. Marques Contribution of Coronavirus-Specific Immunoglobulin G Responses to Complement Overactivation in Patients with Severe Coronavirus Disease 2019 The Journal of Infectious Diseases® 2022;XX:1–12 doi/10.1093/infdis/jiac091/6546404
Castanha PMS, Marques ETA. A Glimmer of Hope: Recent Updates and Future Challenges in Zika Vaccine Development. Viruses. 2020 Nov 30;12(12):1371. doi: 10.3390/v12121371.PMID: 33266129
Castanha PMS and Ernesto T A Marques. Zika vaccines: can we solve one problem without creating another one? Lancet Infect Dis; May 18, 2021 DOI:https://doi.org/10.1016/S1473-3099(20)30768-4
PMS Castanha, ETA Marques Vaccine development during global epidemics: the Zika experience. The Lancet. Infectious Diseases (2020)
Isabel Rodriguez-Barraquer, Federico Costa, Eduardo JM Nascimento, Nivison Nery, Priscila MS Castanha, Gielson Almeida Sacramento, Jaqueline Cruz, Mayara Carvalho, Daiana De Olivera, José E Hagan, Haritha Adhikarla, Elsio A Wunder, Danilo F Coêlho, Sasha R Azar, Shannan L Rossi, Nikos Vasilakis, Scott C Weaver, Guilherme S Ribeiro, Angel Balmaseda, Eva Harris, Maurício L Nogueira, Mitermayer G Reis, Ernesto TA Marques, Derek AT Cummings, Albert I Ko; Impact of preexisting dengue immunity on Zika virus emergence in a dengue endemic region, Science 363 (6427), 607-610 (2019)
Marques ETA, Burke DS. Tradition and innovation in development of a Zika vaccine. Lancet. (2018)
Nascimento, Eduardo J.M. ; Huleatt, James W. ; Cordeiro, Marli T. ; Castanha, Priscila M.S. ; George, James K. ; Grebe, Eduard ; Welte, Alex ; Brown, Monique ; Burke, Donald S. ; Marques, Ernesto T.A. . Development Of Antibody Biomarkers Of Long Term And Recent Dengue Virus Infections. Journal Of Virological Methods, v. 257, p. 62-68, (2018).
Magalhaes T, Braga C, Cordeiro MT, Oliveira ALS, Castanha PMS, Maciel APR, Amancio NML, Gouveia PN, Peixoto-da-Silva VJ Jr, Peixoto TFL, Britto H, Lima PV, Lima ARS, Rosenberger KD, Jaenisch T, Marques ETA. Zika virus displacement by a chikungunya outbreak in Recife, Brazil. PLoS Negl Trop Dis 11(11):e0006055. (2017)
Castanha PMS, Nascimento EJM, Braga C, Cordeiro MT, de Carvalho OV, de Mendonça LR, Azevedo EAN, França RFO, Dhalia R, Marques ETA. Dengue Virus-Specific Antibodies Enhance Brazilian Zika Virus Infection. J Infect Dis 215:781-785. (2017)
Palma ML, Duangkhae P, Douradinha B, Viana IFT, Rigato PO, Dhalia R, Mailliard RB, Barratt-Boyes SM, Nascimento EJM, Oshiro TM, da Silva Duarte AJ, Marques ETA. Development of potent class II transactivator gene delivery systems capable of inducing de novo MHC II expression in human cells, in vitro and ex vivo. Gene Ther 24:342-352. (2017)
Jaenisch T, Rosenberger KD, Brito C, Brady O, Brasil P, Marques ET. (2017). Risk of microcephaly after Zika virus infection in Brazil, 2015 to 2016. Bull World Health Organ 95:191-198.
Castanha PM, Braga C, Cordeiro MT, Souza AI, Silva CD, Martelli CT, van Panhuis WG, Nascimento EJ, Marques ET. (2016). Placental transfer of dengue-specific antibodies and kinetics of dengue infection enhancing-activity in Brazilian infants. J Infect Dis doi: 10.1093/infdis/jiw143.
Cordeiro MT, Pena LJ, Brito CA, Gil LH, Marques ET. (2016). Positive IgM for Zika virus in the cerebrospinal fluid of 30 neonates with microcephaly in Brazil. Lancet doi: 10.1016/S0140-6736(16)30253-7.
Cordeiro MT, Brito CA, Pena LJ, Castanha PM, Gil LH, Lopes KG, Dhalia R, Meneses JA, Ishigami AC, Mello LM, Alencar LX, Guarines KM, Rodrigues LC, Marques ET. (2016). Results of a Zika Virus (ZIKV) Immunoglobulin M-Specific Diagnostic Assay Are Highly Correlated With Detection of Neutralizing Anti-ZIKV Antibodies in Neonates With Congenital Disease. J Infect Dis 214:1897-1904.
Araujo TVB, Rodrigues LC, Ximenes RA, Miranda-Filho DB, Montarroyos UR, Melo APL, Valongueiro S, Militao de Albuquerque, MDP, Souza WV, Braga C, Filho SPB, Vazquez E, Cruz DC, Bezerra LA, Henriques CMP, Castanha PM, Cordeiro MT, Dhalia R, Marques-Junior ET, Martelli CMT. (2016). Microcephaly and Zika infection: Preliminary Report of a Case- Control Study. Lancet Infect Dis 16:1356-1363.
https://www.ncbi.nlm.nih.gov/myncbi/ernesto.marques.1/bibliography/public/
