About the Harris Research Program

Projects

One major focus of the Harris Research Program is on studies of arboviral disease in humans, including:

1. Antibody and B cell responses and correlates of protection

2. Systems immunology profiling of the innate response

3. Viral evolution, fitness, and intra-host diversity

4. Viral pathogenesis: the role of non-structural 1 (NS1) protein in vascular leak

Professor Harris’ international work focuses on laboratory-based and epidemiological studies of dengue, Zika, chikungunya, and influenza in endemic Latin American countries, particularly in Nicaragua, where she has been working closely with our Nicaraguan colleagues for over 30 years. Long-term collaborations include clinical, biological, and immunological studies of severe disease through a 20-year pediatric hospital-based study; a 20-year ongoing pediatric cohort study of dengue, Zika, chikungunya, and influenza transmission in Managua; and a cluster randomized controlled trial of evidence-based community-derived interventions to prevent and control arboviral diseases.

Preprinted Publications

Complement-dependent virion lysis mediated by dengue-Zika virus cross-reactive antibodies correlates with protection from severe dengue disease
Antonio G. Dias Jr., Elias Duarte, Jose Victor Zambrana, Jaime A. Cardona-Ospina, Sandra Bos, Vicky Roy, Guillermina Kuan, Angel Balmaseda, Galit Alter, Eva Harris
medRxiv [Preprint] 2024.06.03.24308395; doi: https://doi.org/10.1101/2024.06.03.24308395

Antibodies targeting Crimean-Congo hemorrhagic fever virus GP38 limit vascular leak and viral spread.
Pahmeier F, Monticelli SR, Feng X, Hjorth CK, Wang A, Kuehne AI, Bakken RR, Batchelor TG, Lee SE, Middlecamp M, Stuart L, Abelson DM, McLellan JS, Biering SB, Herbert AS, Chandran K, Harris E.
bioRxiv [Preprint]. 2024 May 23:2024.05.23.595578. doi: 10.1101/2024.05.23.595578.

Inapparent primary dengue virus infections reveal hidden serotype-specific epidemiological patterns and spectrum of infection outcome: a cohort study in Nicaragua.
Bos S, Zambrana JV, Duarte E, Graber AL, Huffaker J, Montenegro C, Premkumar L, Gordon A, Balmaseda A, Harris E.
medRxiv [Preprint]. 2024 Apr 8:2024.04.05.24305281. doi: 10.1101/2024.04.05.24305281. PMID: 38633800

Dengue severity by serotype in 19 years of pediatric clinical studies in Nicaragua.
Narvaez F, Montenegro C, Juarez JG, Zambrana JV, Gonzalez K, Arguello S, Barrios F, Ojeda S, Plazaola M, Sanchez N, Camprubi D, Kuan G, Bailey GP, Harris E, Balmaseda A.
medRxiv [Preprint]. 2024 Feb 13:2024.02.11.24302393. doi: 10.1101/2024.02.11.24302393. PMID: 38405964

Yellow fever disease severity and endothelial dysfunction are associated with elevated serum levels of viral NS1 protein and syndecan-1.
de Sousa FTG, Warnes CM, Manuli ER, Ng A, D'Elia Zanella LGFAB, Ho YL, Bhat S, Romano CM, Beatty PR, Biering SB, Kallas EG, Sabino EC, Harris E.
medRxiv [Preprint]

Epidemics of chikungunya, Zika, and COVID-19 reveal bias in case-based mapping.
Bustos Carrillo FA, Mercado BL, Monterrey JC, Collado D, Saborio S, Miranda T, Barilla C, Ojeda S, Sanchez N, Plazaola M, Laguna HS, Elizondo D, Arguello S, Gajewski AM, Maier HE, Latta K, Carlson B, Coloma J, Katzelnick L, Sturrock H, Balmaseda A, Kuan G, Gordon A, Harris E. medRxiv [Preprint].

Recent Publications

The ApoA1-mimetic peptide 4F blocks flavivirus NS1-triggered endothelial dysfunction and protects against lethal dengue virus challenge
Carneiro PH, Jimenez-Posada EV, Lopes E, Mohana-Borges R, Biering SB, Harris E.
Antiviral Res. 2024 Sep 9:106002. doi: 10.1016/j.antiviral.2024.106002.

Obesity is associated with increased pediatric dengue virus infection and disease: A 9-year cohort study in Managua, Nicaragua.
Mercado-Hernandez R, Myers R, Bustos Carillo FA, Zambrana JV, López B, Sanchez N, Gordon A, Balmaseda A, Kuan G, Harris E.
Clin Infect Dis. 2024 Jul 15:ciae360. doi: 10.1093/cid/ciae360.

Primary exposure to Zika virus is linked with increased risk of symptomatic dengue virus infection with serotypes 2, 3, and 4, but not 1.
Zambrana JV, Hasund CM, Aogo R, Bos S, Arguello S, Gonzalez K, Collado D, Miranda T, Kuan G, Gordon A, Balmaseda A, Katzelnick L, Harris E. Sci Transl Med. 2024 May 29;16(749):eadn2199. doi:10.1126/scitranslmed.adn2199

The inflammasome pathway is activated by dengue virus non-structural protein 1 and is protective during dengue virus infection.
Wong MP, Juan EYW, Pahmeier F, Chelluri SS, Wang P, Castillo-Rojas B, Blanc SF, Biering SB, Vance RE, Harris E.
PLoS Pathog. 2024 Apr 25;20(4):e1012167. doi: 10.1371/journal.ppat.1012167.

Longitudinal analysis of post-acute chikungunya-associated arthralgia in children and adults: A prospective cohort study in Managua, Nicaragua (2014-2018).
Warnes CM, Bustos Carrillo FA, Zambrana JV, Lopez Mercado B, Arguello S, Ampié O, Collado D, Sanchez N, Ojeda S, Kuan G, Gordon A, Balmaseda A, Harris E.
PLoS Negl Trop Dis. 2024 Feb 28;18(2):e0011948. doi: 10.1371/journal.pntd.0011948.

Protection against symptomatic dengue infection by neutralizing antibodies varies by infection history and infecting serotype.
Bos S, Graber AL, Cardona-Ospina JA, Duarte EM, Zambrana JV, Ruíz Salinas JA, Mercado-Hernandez R, Singh T, Katzelnick LC, de Silva A, Kuan G, Balmaseda A, Harris E.
Nat Commun. 2024 Jan 9;15(1):382. doi: 10.1038/s41467-023-44330-8.

SARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via integrins and TGF-β signaling
Biering SB, Gomes de Sousa FT, Tjang LV, Pahmeier F, Zhu C, Ruan R, Blanc SF, Patel TS, Worthington CM, Glasner DR, Castillo-Rojas B, Servellita V, Lo NTN, Wong MP, Warnes CM, Sandoval DR, Clausen TM, Santos YA, Fox DM, Ortega V, Näär AM, Baric RS, Stanley SA, Aguilar HC, Esko JD, Chiu CY, Pak JE, Beatty PR, Harris E.
Nat Commun. 2022 Dec 9;13(1):7630. doi: 10.1038/s41467-022-34910-5.

Molecular Determinants of Tissue Specificity of Flavivirus Nonstructural Protein 1 Interaction with Endothelial Cells.
Lo NTN, Roodsari SZ, Tin NL, Wong MP, Biering SB, Harris E.
J Virol. 2022 Sep 15:e0066122. doi: 10.1128/jvi.00661-22.
[pdf]

Genome-wide, bidirectional CRISPR screens identify mucins as critical host factors modulating SARS-CoV-2 infection
Biering SB, Sarnik SA, Wang E, Zengel JR, Leist SR, Schäfer A, Sathyan V, Hawkins P, Okuda K, Tau C, Jangid AR, Duffy CV, Wei J, Gilmore RC, Alfajaro MM, Strine MS, Nguyenla X, Van Dis E, Catamura C, Yamashiro LH, Belk JA, Begeman A, Stark JC, Shon DJ, Fox DM, Ezzatpour S, Huang E, Olegario N, Rustagi A, Volmer AS, Livraghi-Butrico A, Wehri E, Behringer RR, Cheon DJ, Schaletzky J, Aguilar HC, Puschnik AS, Button B, Pinsky BA, Blish CA, Baric RS, O'Neal WK, Bertozzi CR, Wilen CB, Boucher RC, Carette JE, Stanley SA, Harris E, Konermann S, Hsu PD.
Nat Genet. 2022 Aug;54(8):1078-1089. doi: 10.1038/s41588-022-01131-x.

Sulfated β-glucan from Agaricus subrufescens inhibits flavivirus infection and nonstructural protein 1-mediated pathogenesis.
Sousa FTG, Biering SB, Patel TS, Blanc SF, Camelini CM, Venzke D, Nunes RJ, Romano CM, Beatty PR, Sabino EC, Harris E.
Antiviral Res. 2022 Jul;203:105330. doi: 10.1016/j.antiviral.2022.105330.

Antibody Fc characteristics and effector functions correlate with protection from symptomatic dengue virus type 3 infection.
Dias AG Jr, Atyeo C, Loos C, Montoya M, Roy V, Bos S, Narvekar P, Singh T, Katzelnick LC, Kuan G, Lauffenburger DA, Balmaseda A, Alter G, Harris E.
Sci Transl Med. 2022 Jun 29;14(651):eabm3151. doi: 10.1126/scitranslmed.abm3151.

Epidemiologic Features of Acute Pediatric Diarrhea in Managua, Nicaragua, from 2011 to 2019.
Zambrana JV, Bustos Carrillo FA, Ojeda S, Lopez Mercado B, Latta K, Schiller A, Kuan G, Gordon A, Reingold A, Harris E.
Am J Trop Med Hyg. 2022 Jun 15;106(6):1757-1764. doi: 10.4269/ajtmh.21-0793.

Development and Implementation of Dried Blood Spot-based COVID-19 Serological Assays for Epidemiologic Studies
Wong MP, Meas MA, Adams C, Hernandez S, Green V, Montoya M, Hirsch BM, Horton M, Quach HL, Quach DL, Shao X, Fedrigo I, Zermeno A, Huffaker J, Montes R, Madden A, Cyrus S, McDowell D, Williamson P, Contestable P, Stone M, Coloma J, Busch MP, Barcellos LF, Harris E. (2022)
Microbol. Spectr. 2022 May 25;e0247121. doi: 10.1128/spectrum.02471-21

Disassembly of Intercellular Junctions Leading to Barrier Dysfunction and Vascular Leak in a GSK-3β-Dependent Manner.
Puerta-Guardo H, Biering SB, de Sousa FTG, Shu J, Glasner DR, Li J, Blanc SF, Beatty PR, Harris E. (2022)
Pathogens. 2022 May 24;11(6):615. doi: 10.3390/pathogens11060615.

DengueChat: A Social and Software Platform for Community-based Arbovirus Vector Control.
Holston J, Suazo-Laguna H, Harris E, Coloma J. (2021)
Am J Trop Med Hyg. 2021 Oct 11;105(6):1521-1535. doi: 10.4269/ajtmh.20-0808.

Dengue and Zika virus infections in children elicit cross-reactive protective and enhancing antibodies that persist long term.
Katzelnick LC, Zambrana JV, Elizondo D, Collado D, Garcia N, Arguello S, Mercado JC, Miranda T, Ampie O, Mercado BL, Narvaez C, Gresh L, Binder RA, Ojeda S, Sanchez N, Plazaola M, Latta K, Schiller A, Coloma J, Carrillo FB, Narvaez F, Halloran ME, Gordon A, Kuan G, Balmaseda A, Harris E. (2021)
Science Translational Medicine 2021 Oct 6;13(614):eabg9478. doi: 10.1126/scitranslmed.abg9478.

Structural basis for antibody inhibition of flavivirus NS1-triggered endothelial dysfunction
Biering SB & Akey DL, Wong MP, Brown WC, Lo NTN, Puerta-Guardo H, Tramontini Gomes de Sousa F, Wang C, Konwerski JR, Espinosa DA, Bockhaus NJ, Glasner DR, Li J, Blanc SF, Juan EY, Elledge SJ, Mina MJ, Beatty PR, Smith JL, Harris E. (2021)
Science 2021 Jan 8;371(6525):194-200. doi: 10.1126/science.abc0476.
[pdf]

Zika virus infection enhances future risk of severe dengue disease.
Katzelnick LC, Narvaez C, Arguello S, Lopez Mercado B, Collado D, Ampie O, Elizondo D, Miranda T, Bustos Carillo F, Mercado JC, Latta K, Schiller A, Segovia-Chumbez B, Ojeda S, Sanchez N, Plazaola M, Coloma J, Halloran ME, Premkumar L, Gordon A, Narvaez F, de Silva AM, Kuan G, Balmaseda A, Harris E (2020)
Science 2020 Aug 28;369(6507):1123-1128. doi: 10.1126/science.abb6143.

Characterization of the Type-Specific and Cross-Reactive B Cell Responses Elicited by a Live-Attenuated Tetravalent Dengue Vaccine
Michlmayr D, Andrade P, Nascimento EJM,  Parker A, Narvekar P, Dean HJ, Harris E (2020)
J Infect Dis 2020 Jun 4. doi:10.1093/infdis/jiaa346

Primary and secondary dengue virus infections elicit similar memory B cell responses but breadth to other serotypes and cross-reactivity to Zika virus is higher in secondary dengue. Andrade P, Narvekar P, Montoya M, Michlmayr D, Balmaseda A, Coloma J, Harris E. (2020)
J Infect Dis 2020 Mar 20. doi: 10.1093/infdis/jiaa120

Age-dependent manifestations and case definitions of paediatric Zika: a prospective cohort study.
Burger-Calderon R, Bustos Carrillo F, Gresh L, Ojeda S, Sanchez N, Plazaola M, Katzelnick L, Lopez Mercado B,Carey Monterrey J, Elizondo D, Arguello S, Nuñez A, Gordon A, Balmaseda A, Kuan G, Harris E. (2019)
Lancet Infect Dis. 2019 Dec 20. doi: 10.1016/S1473-3099(19)30547-X
[pdf]

Tracking the polyclonal neutralizing antibody response to a dengue virus serotype 1 type-specific epitope across two populations in Asia and the Americas
Andrade DV, Warnes C, Young E, Katzelnick LC, Balmaseda A, de Silva AM, Baric RS, Harris E. (2019)
Sci Rep. 2019 Nov 7. doi: 10.1038/s41598-019-52511-z10.1038/s41598-019-52511-z
[pdf]

Increased serum sialic acid is associated with morbidity and mortality in a murine model of dengue disease.
Espinosa DA, Beatty PR, Puerta-Guardo H, Islam MN, Belisle JT, Perera R, Harris E. (2019)
J Gen Virol. 2019 Sep 17. doi: 10.1099/jgv.0.001319
[pdf]

Endocytosis of flavivirus NS1 is required for NS1-mediated endothelial hyperpermeability and is abolished by a single N-glycosylation site mutation.
Wang C, Puerta-Guardo H, Biering SB, Glasner DR, Tran EB, Patana M1 Gomberg TA, Malvar C, Lo NTN, Espinosa DA, Harris E. (2019)
PLoS Pathog. 2019 Jul 19. doi: 10.1371/journal.ppat.1007938
[pdf]

Impact of pre-existing dengue immunity on human antibody and memory B cell responses to Zika.
Andrade P, Gimblet-Ochieng C, Modirian F, Collins M, Cárdenas M, Katzelnick LC, Montoya M, Michlmayr D, Kuan G, Balmaseda A, Coloma J, de Silva AM, Harris E. (2019)
Nature Comm. 2019 Feb 26. doi: 10.1038/s41467-019-08845-3.
[pdf]

Magnitude and Functionality of the NS1-Specific Antibody Response Elicited by a Live-Attenuated Tetravalent Dengue Vaccine Candidate.
Sharma M, Glasner DR, Watkins H, Puerta-Guardo H, Kassa Y, Egan MA, Dean H, Harris E. (2019)
J. Infect. Dis. 2019 Feb 19. doi:10.1093/infdis/jiz081.
[pdf]

Flavivirus NS1 triggers tissue-specific vascular endothelial dysfunction reflecting disease tropism.
Puerta-Guardo H, Glasner DR, Espinosa DA, Biering SB, Patana M, Ratnasiri K, Wang C, Beatty PR, Harris E. (2019)
Cell Rep. 2019 Feb 5. doi: 10.1016/j.celrep.2019.01.036
[pdf]

Epidemiological Evidence for Lineage-Specific Differences in the Risk of Inapparent Chikungunya Virus Infection.
Bustos Carrillo F, Collado D, Sanchez N, Ojeda S, Lopez Mercado B, Burger-Calderon R, Gresh L, Gordon A, Balmaseda A, Kuan G, Harris E. (2019)
J Virology. 2019 Feb 5; 93(4). doi:10.1128/JVI.01622-18
[pdf]

Prior dengue virus infection and risk of Zika: A pediatric cohort in Nicaragua.
Gordon A, Gresh L, Ojeda S, Katzelnick LC, Sanchez N, Mercado JC, Chowell G, Lopez B, Elizondo D, Coloma J, Burger-Calderon R, Kuan G, Balmaseda A, Harris E. (2019)
PLoS Medicine. 2019 Jan 22; 16(1):e1002726. doi: 10.1371/journal.pmed.1002726
[pdf]

Cyclic Dinucleotide-Adjuvanted Dengue Virus Nonstructural Protein 1 Induces Protective Antibody and T Cell Responses.
Espinosa DA, Beatty PR, Reiner GL, Sivick KE, Hix Glickman L, Dubensky TW Jr, Harris E. (2019)
J. Immunol. 2019 Jan 18. doi:10.4049/jimmunol.1801323
[pdf]

Dynamics and determinants of the force of infection of dengue virus from 1994 to 2015 in Managua, Nicaragua.
Katzelnick LC, Ben-Shachar R, Mercado JC, Rodriguez-Barraquer I, Elizondo D, Arguello S, Nuñez A, Ojeda S, Sanchez N, Lopez Mercado B, Gresh L, Burger-Calderon R, Kuan G, Gordon A, Balmaseda A, Harris E. (2018)
PNAS. 2018 Oct 16; 115(42):10762-10767. doi:10.1073/pnas.1809253115.
[pdf]

Comprehensive innate immune profiling of chikungunya virus infection in pediatric cases.
Michlmayr D, Pak TR, Rahman AH, Amir ED, Kim EY, Kim-Schulze S, Suprun M, Stewart MG, Thomas GP, Balmaseda A, Wang L, Zhu J, Suaréz-Fariñas M, Wolinsky SM, Kasarskis A, Harris E. (2018)

Recent advances in understanding the adaptive immune response to Zika virus and the effect of previous flavivirus exposure.
Andrade DV, Harris E. (2018)
Virus Res. 2018 Aug 2; 254:27-33. doi:10.1016/j.virusres.2017.06.019.
[pdf]

Longitudinal Analysis of Antibody Cross-neutralization Following Zika Virus and Dengue Virus Infection in Asia and the Americas.
Montoya M, Collins M, Dejnirattisai W, Katzelnick LC, Puerta-Guardo H, Jadi R, Schildhauer S, Supasa P, Vasanawathana S, Malasit P, Mongkolsapaya J, de Silva AD, Tissera H, Balmaseda A, Screaton G, de Silva AM, Harris E. (2018)
J. Infect. Dis. 2018 Jul 13; 218(4):536-545. doi:10.1093/infdis/jiy164.
[pdf]

Featured Publications

Seroprevalence, risk factor, and spatial analysis of Zika virus infection after the 2016 epidemic in Managua, Nicaragua. 
Zambrana JV, Bustos F, Burger-Calderon R, Collado D, Jairo Sanchez N, Ojeda S, Plazaola M, Lopez B, Arguello S, Elizondo D, Aviles W, Kuan G, Balmaseda A, Gordon A, Harris E. (2018)
Proc. Natl. Acad. Sci. USA. 2018 Sep 11;115(37):9294-9299. doi: 10.1073/pnas.1804672115. Epub 2018 Aug 27.

Comprehensive innate immune profiling of chikungunya virus infection in pediatric cases.
Michlmayr D., Pak T.R., Rahman A.H., Amir E.D., Kim E.Y., Kim-Schulze S., Suprun M., Stewart M.G., Thomas G.P., Balmaseda A., Wang L., Zhu J., Suaréz-Fariñas M., Wolinsky S.M., Kasarskis A., Harris E. (2018)
Mol. Syst. Biol. 2018 Aug 27;14(8):e7862. doi: 10.15252/msb.20177862.

Differences in transmission and disease severity between two successive waves of chikungunya.
Gordon, A., Gresh, L., Ojeda, S., Chowell-Puente, G., Gonzalez, K., Sanchez, N., Saborio, S., Mercado, J.C., Kuan, G., Balmaseda, A., and Harris, E. (2018)
Clin. Infect. Dis. 2018 Apr 25. doi: 10.1093/cid/ciy356. [Epub ahead of print].

Antibody-dependent enhancement of severe dengue disease in humans.
Katzelnick., L. Gresh, L, Halloran, M.E., Mercado, J.C., Kuan, G., Gordon, A., Balmaseda, A., and Harris, E. (2017)
Science. 358(6365):929-932.

Longitudinal analysis of antibody cross-neutralization following Zika and dengue virus infection in Asia and the Americas
Montoya, M., Collins, M., Dejnirattisai, W., Katzelnick, L.C., Puerta-Guardo, H., Jadi, R., Schildhauer, S., Supasa, P., Vasanawathana, S., Malasit, P., Mongkolsapaya, J., de Silva, A.D., Tissera, H., Balmaseda, A., Screaton, G., de Silva, A.M., Harris, E. (2018)
J. Infect. Dis. 218(4):536-545.

CD14+ CD16+ monocytes are the main targets of Zika virus infection in peripheral blood mononuclear cells in a paediatric study in Nicaragua.
Michlmayr, D., Andrade, P., Gonzalez, K., Balmaseda, A., and Harris E. (2017)
Nat Microbiol. 2(11):1462-1470. 2017.

Dengue virus NS1 cytokine-independent vascular leak is dependent on endothelial glycocalyx integrity. 
Glasner, D.R., Ratnasiri, K., Puerta-Guardo, H., Beatty, P.R., and Harris, E. (2017)
PLoS Pathog. 13(11):e1006673.

Analysis of individuals from a dengue-endemic region helps define the footprint and repertoire of antibodies targeting dengue virus 3 type-specific epitopes.
Andrade, D.V., Katzelnick, L.C., Widman, D.G., Balmaseda, A., de Silva A.M., Baric, R.S., and Harris, E. (2017)
mBio. 8(5):e01205-17.

Intrahost selection pressures drive rapid dengue virus microevolution in acute human infections.
Parameswaran, P., Wang, C., Trivedi, S.B., Eswarappa, M., Montoya, M., Balmaseda, A., and Harris, E. (2017)  
Cell Host Microbe. 22(3):400-410.e5.

Zika virus targets different primary human placental cells, suggesting two routes for vertical transmission. 
Tabata, T., Petitt, M., Puerta-Guardo, H., Michlmayr, D., Wang, C., Fang-Hoover, J., Harris, E.* and Pereira, L.* (2016)
Cell Host Microbe. In press (Epub July 18, 2016) S1931-3128(16)30300-6. doi: 10.1016/j.chom.2016.07.002. *Co-corresponding authors. 

Dengue virus NS1 disrupts the endothelial glycocalyx, leading to hyperpermeability. 
Puerta-Guardo, H., Glasner, D.R., and Harris, E. (2016)
PLoS Pathog.12(7):e1005738.

Dengue virus non-structural protein 1 (NS1) triggers vascular leak that can be inhibited by anti-NS1 antibodies. 
Beatty, P.R., Puerta Guardo, H., Killingbeck, S., Glasner, D., Hopkins, K., and Harris, E. (2015)
Sci Transl Med. 7:304ra141.

Evidence based community mobilization for dengue prevention in Nicaragua and Mexico (Camino Verde, the Green Way): cluster randomized controlled trial.
Andersson, N., Nava-Aguilera, E., Arostegui, J., Morales-Perez, A., Suazo-Laguna, H., Legorreta-Soberanis, J., Hernandez-Alvarez, C., Fernandez-Salas, I., Balmaseda, A., Cortés-Guzmán, A.J., Coloma, J., Ledogar, R.J., and Harris, E. (2015)  
BMJ. 351:h3267.

Contact Us

To reach the Harris Research Program, email Dr. Eva Harris at eharris (at) berkeley (dot) edu