Marcelo B. Sztein, MD

1. Toapanta, F.R., Bernal, P.J., Fresnay, S., Magder, L.S., Darton, T.C., Jones, C., Waddington, C.S., Blohmke, C.J., Angus, B., Levine, M.M., Pollard, A.J., Sztein, M.B. Oral Challenge with Wild-type Salmonella Typhi Induces Distinct Changes in B cell Subsets in Individuals Who Develop Typhoid Disease.  PLoS Negl Trop Dis.  10(6): e0004766, 2016. PMID: 27300136. PMC4907489.
2. Wahid, R., Fresnay, S., Levine, M.M. and Sztein, M.B. Cross-reactive multifunctional CD4+ T cell responses against Salmonella enterica serovars Typhi, Paratyphi A and Paratyphi B in humans following immunization with live oral typhoid vaccine Ty21a. Immunol.  173: 87-95, 2016. PMID: 27634430. PMC5322816
3. McArthur, M.A., Chen, W.H., Magder, L.S., Levine, M.M., Sztein, M.B. Impact of CD4+ T Cell Responses on Clinical Outcome following Oral Administration of Wild-type Enterotoxigenic Escherichia coli in Humans.  PLoS Negl Trop Dis. 11(1): e0005291, 2017.  PMID: 28103236. 
4. Fresnay, S., McArthur, M.A., Magder, L.S., Darton, T.C., Jones, C., Waddington, C.S., Blohmke, C.J., Angus, B., Levine, M.M., Pollard, A.J., Sztein, M.B. Importance of Salmonella Typhi-responsive CD8+ T cell immunity in a human typhoid fever challenge model. Frontiers in Immunology. 8: 208, 2017.  PMID: 28303138.  
5. Salerno-Goncalves, R., Luo, D., Fresnay, S., Magder, L.S., Darton, T.C., Jones, C., Waddington, C.S., Blohmke, C.J., Angus, B., Levine, M.M., Pollard, A.J., Sztein, M.B. Challenge of humans with wild-type Salmonella enterica serovar Typhi elicits changes in the activation and homing characteristics of Mucosal-Associated Invariant T cells. Frontiers in Immunology. 8: 398, 2017. PMID: 28428786.  
6. Booth, J.S., Patil, S.A., Ghazi, L., Barnes, R., Fraser, C.M., Fasano, A., Greenwald, B.D. and Sztein, M.B. Systemic and terminal ileum mucosal immunity elicited by oral immunization with the Ty21a typhoid vaccine in humans.  Journal editorial “Location Matters in Defining T Cell–mediated Immunity in Response to Salmonella Typhi Vaccination” by Karen L. Edelblum.  Cellular and Molecular Gastroenterology and Hepatology.  4: 419-437, 2017.  PMID: 29022005. PMC5626924
7. Sztein, M.B. Is a human CD8⁺ T cell vaccine possible, and if So, what would it take? CD8+ T-mediated protective immunity and vaccination against enteric bacteria.  Immune Memory and Vaccines: Great Debates. S. Crotty and R. Ahmed, editors. Cold Spring Harbor (CSH).  Perspectives series.  Cold Spring Harbor Perspect Biol. 10: a029546, 2018. PMID: 29254983. 
8. Lyke, K.E., Dabo, A., Arama, C., Diarra, I., Plowe, C.V., Doumbo, O.K., Sztein, M.B. Long-term Maintenance of Multifunctional CD4 T Cell Memory Responses to Malaria Antigens in Malian Children Co-infected with Schistosoma haematobium. Immunol. 8: 1995, 2018. PMID: 29449839.  PMC5799235.
9. Rudolph, M.E., McArthur, M.A., Magder, L., Barnes, R.S., Chen, W.H., Sztein, M.B. Differences Between Pediatric and Adult T Cell Responses to in vitro SEB Stimulation. Immunology 9: 498, 2018. PMID: 29616025.  PMC5869216.
10. Booth, J.S., Goldberg, E., Patil, S.A., Barnes, R.S., Greenwald, B.D., Sztein, M.B. Effect of live oral attenuated Typhoid vaccine, Ty21a, on systemic and terminal ileum mucosal CD4+ T_M responses in humans.  International Immunology. 31: 101-116, 2019. PMID: 30346608.     
11. Rudolph, M.E., McArthur, M.A., Magder, L.S., Barnes, R.S., Chen, W.H., Sztein, M.B. Diversity of Salmonella Typhi-Responsive CD4 and CD8 T cells before and after Ty21a Typhoid Vaccination in Children and Adults. International Immunology. 31: 315-333, PMID: 30951606. PMC6484895
12. Rudolph, M.E., McArthur, M.A., Magder, L.S., Barnes, R.S., Chen, W.H., Sztein, M.B. Age-Associated Heterogeneity of Ty21a-Induced T Cell Responses to HLA-E Restricted Salmonella Typhi Antigen Presentation. Frontiers in Immunology. 10: 257, 2019. PMID: 30886613. PMC6409365.
13. Booth, J.S., Goldberg, E., Patil, S.A., Greenwald, B.D., Sztein, M.B. Association between S. Typhi-specific memory CD4+ and CD8+ T responses in the terminal ileum mucosa and in peripheral blood elicited by the live oral typhoid vaccine Ty21a in humans. Human Vaccines and Immunotherapeutics.  6: 1-12, 2019.  PMID: 30836838. PMC6663141.
14. Wahid, R., Kotloff, K.L., Levine, M.M., Sztein, M.B. Cell mediated immune responses elicited in volunteers following immunization with candidate live oral Salmonella enterica serovar Paratyphi A attenuated vaccine strain CVD 1902. Clinical Immunology. 201: 61-69, 2019 PMID: 30849494. PMC6959129.
15. Booth, J.S., Goldberg, E., Barnes, R.S., Greenwald, B.D., Sztein, M.B. Resident memory CD4+ T cells elicited in the human terminal ileum lamina propria and epithelial compartments by oral typhoid vaccination. Translational Medicine. 18: 102, 2020.  PMID: 32098623. PMC7043047.   
16. Sztein, M.B., Bafford, A.C. and Salerno-Goncalves, R. Salmonella enterica serovar Typhi exposure elicits cell type-specific epigenetic changes in the human gut. Scientific Reports. 10: 13581, 2020. PMID: 32788681. PMC7423951. 
17. Rapaka, R.R, Wahid, R., Fresnay, S., Booth, J.S., Darton, T.C., Jones, C., Waddington, C.S., Levine, M.M., Pollard, A.J., Sztein, M.B. Human Salmonella Typhi exposure generates differential overlapping multifunctional cross-reactive T cell memory responses against Salmonella Paratyphi and invasive nontyphoidal Salmonella.  Clinical & Translational Immunology. 9: e1178, 2020. PMID: 33005416. PMC7512505.
18. Booth, J.S., Goldberg, E., Patil, S.A., Barnes, R.S., Greenwald, B.D. and Sztein, M.B. Age-dependency of terminal ileum tissue resident memory T cell responsiveness profiles to Typhi following oral Ty21a immunization in humans.  Immunity and Ageing. 18: 19, 2021. PMID: 33874975. PMC8053564. Editor’s pick.
19. Salerno-Gonçalves, R., Rezwan, T., Luo, D., Tettelin, H. and Sztein, M.B. B cells control mucosal-associated invariant T cell responses to Salmonella enterica serovar Typhi infection through the CD85j HLA-G receptor. Frontiers in Immunology. 12: 728685, 2021. PMID: 34659215. PMC8517411.
20. Salerno-Gonçalves, R., Fresnay, S., Magder, L., Darton, T.C., Waddington, C.S., Blohmke, C.J., Angus, B., Levine, M.M., Pollard, A.J., Sztein, M.B. Mucosal-Associated Invariant T cells exhibit distinct functional signatures associated with protection against typhoid fever. Cellular Immunology. 378: 104572, 2022.  PMID: 35772315.  

Dr. Sztein has made important contributions to the fields of the host immune responses to infectious diseases and vaccine development. To date, he has authored or co-authored 265 manuscripts in prestigious peer-reviewed journals and written 33 invited chapters (Google Scholar Citation Report [update April 7, 2026]: Sum of Times Cited: 18,330; Times Cited since 2021: 3,865; H-index: 79). Current projects encompass the study of systemic and gastrointestinal mucosal immune responses in preclinical models and in specimens from volunteers participating in immunization and challenge studies with wild-type organisms and in vaccine trials.  These include studies involving genetically engineered vaccine strains such as attenuated S. Typhi, S. Paratyphi A, S. Paratyphi B and Shigella (alone or as a carrier of foreign genes), invasive non-typhoidal Salmonella (iNTS), V. cholera, Enteroaggregative E. coli, ETEC, Plasmodium falciparum, as well as Dengue virus, F. tularensis, Ebola, influenza, hepatitis and, more recently, SARS-CoV-2.

He is regularly invited to serve in NIH grant review panels (either as a member or as a chair), as well as those convened by foundations and other granting agencies. He has been continuously funded by NIH and other sources since 1986. These include federal as well as private entities such as non-profit organizations (e.g., PATH, Bill and Melinda Gates Foundation) and biotechnology and pharmaceutical companies. Regarding NIH, he has been successful in obtaining funds using a variety of funding mechanisms (e.g., R21, R01, U19, U54, contracts). Dr. Sztein has extensive experience in managing large multidisciplinary teams of investigators as part of NIH contracts and U19 grants.

Throughout his career, he considered one of his primary duties the training and mentoring of students and post-doctoral fellows (both from the US and abroad, particularly from developing nations), as well as to mentor young and mid-career faculty, including multiple career development award recipients. Over the past 3 decades he has directly mentored and supervised ~30 postdoctoral fellows, medical fellows, graduate students and visiting scientists from the U.S. and from research centers overseas (e.g., Uruguay, Mali). The vast majority of these mentees are currently working in the biomedical sciences, including academia, Government, industry and non-profit organizations. For over 2 decades he has also mentored young faculty.

He is an expert in flow cytometry, having been involved in this field since 1984 and directing flow cytometry core facilities for almost 30 years. About 13 years ago, he was among the first investigators to make use of the state-of-the-art mass cytometer technology (i.e., stable metal isotope-based mass spectroscopy) which allows the measurement of 50 parameters/cell. At present his facility houses 2 Helios (3rd generation) mass cytometers, a 6-way sorter and other analytical flow cytometers that are utilized, among other studies, for vaccines, infectious diseases and cancer-related projects. He has spent considerable amounts of time optimizing mass cytometry panels to make the best use of this transformative technology.

N/A

Active (As PI, Project Leader or Lab. Leader):

2024-2029       National Institutes of Health. T32AI007524. Fellowship Training Program in Vaccinology. Marcelo B. Sztein, PI. Overall T32 Director, Director of the Pathogenesis, Immunology and Antigen Discovery Track, and Permanent member of the Advisory Committee.  07/01/2024 - 06/30/2029. $2,002,673 total costs (all years). Peer-reviewed

2024-2029       National Institutes of Health Grant. U19-AI181108. Cooperative Centers for Human Immunology (CCHI) DAIT, NIAID network entitled “Mechanisms of Mucosal and Systemic Immunity to Vaccination and Infection with Enteric Pathogens in Children and Adults.” Marcelo B. Sztein, P.I. 08.20.2024 - 05/31/2029. $10,012,068 Total costs (all years).  Peer-reviewed.

2026-2030.      National Institutes of Health Grant. R01-AI036525. Immune mechanisms of protection in Salmonella infection in humans. Marcelo B. Sztein, P.I. current support period 04/01/2026 - 03/31/2030.  $2,783,014 total costs (all years for the current period). This R01 grant (Sztein, PI) has been continuously competitively renewed since 1994. Peer-reviewed.

2013-2026.      National Institutes of Health Research Contract. HHSN272201300022I.   Vaccine and Treatment Evaluation Units (VTEU). Karen L. Kotloff, P.I.; Marcelo B. Sztein, Senior Immunologist. 09/16/2013 - 06/30/2026. This contract is based on competitive funding of Task Orders.  Peer-reviewed.

2022-2026       Regeneron Pharmaceuticals, Inc. Contract No: 2021_027852. Differences in Age-associated Gene, Protein and Cellular Profiles in Skin and Immune Cells in the Amish Population. Protocol No: 0000-HV-CES-2002. May Montasser, Protocol PI. Marcelo B. Sztein, Core Director, Leader Immunology Research. 04/01/2022 - 9/30/2025. $496,199 total costs (all years).

2019-2026       National Institutes of Health Contract. 75N93019C00055.  Clinical Core for Collaborative Influenza Vaccine Innovation Centers (CIVICs).  The overall goal of the CIVICs is to develop and advance improved influenza vaccines and novel influenza vaccine approaches through the design, execution and conduct of phase I and II clinical trials and challenge studies in diverse populations.  Justin Ortiz, PI.  Marcelo B. Sztein, Laboratory Leader. 09/16/2019-09/15/2026. This contract is based on competitive funding of Task Orders.

2019-2026       National Institutes of Health Cooperative Agreement (IDIQ). 1UM1AI148689. Implementing Vaccine and Treatment Evaluation Unit (VTEU) Clinical Site.   Karen L. Kotloff, P.I.; Marcelo B. Sztein, Research Laboratory Core Co-Director and member of the Executive Management Team. 08/10/2021 – 11/30/2026.   

Flow Cytometry Core Laboratory

Dr. Sztein, Director

The core facility currently houses four flow cytometer systems described below:

1. Custom Becton-Dickinson LSR-II Flow Cytometer Analyzer.This analyzer is equipped with four lasers (a 100 mW solid state 488 nm blue laser, a 100 mW solid state 640 nm red laser, a 50 mW solid state 405 nm violet laser and a solid-state 552 nm green laser). This system also includes 17 ultra-high sensitivity PMTs (e.g., is capable of collecting 15/16 colors simultaneously) plus forward and side light scatter parameters.  This analyzer is controlled by a state-of-the-art PC-based computer that includes a CD/RW drive and a 1 Tb external hard drive for data archival.
2. Beckman-Coulter MoFlo Astrios EQ Flow Cytometer/Cell Sorter System. This state-of-the art upgradable system is equipped with four lasers (a 405 nm, a 488 nm, a 640 nm and a 100 mW 355 nm JDSU UV). This system also includes 21 ultra-high sensitivity PMTs (e.g., is capable of collecting up to 19 colors simultaneously) plus side scatter and forward scatter to collect light scatter parameters.  The system can be easily upgraded to a max of 32 PMT’s if this becomes necessary due to the development of new fluorochomes, a very likely possibility in coming years. Furthermore, this system is capable of sorting simultaneously 6 distinct cells subsets into a variety of tubes and plates, including 96-well plates for single cell transcriptomics analyses, an important component of this HIPC application.  Of great importance for the proposed studies which include sorting various cell subsets in all Research Projects is that this system features some of the most advanced sorting capabilities of any instrument in the market today concerning cell yield and purity, coupled with automated features to avoid possible cell loses during the sorting process, not an uncommon occurrence.  They include Sort Rescue (auto-stops in case of a clog), IntelliSort II (a fully bead-less drop delay determination and monitoring system) and Auto QC (which automatically sets laser delay for each laser, adjusts PMT voltages, compares CV’s and PMT voltages to pre-determined values and records daily QC).  

Of importance, this system is contained in an integrated Biosafety Cabinet II (Baker) to enable the safe sorting of human cells obtained from healthy individuals participating in the vaccine and challenge studies described in this HIPC application. In addition, technical personnel routinely wear Personal Protective Equipment and use enhanced BSL-II precautions when sorting human cells.  Finally, the system also includes an integrated refrigerated waterbath (ThermoFisher Scientific) for the collection of sorted cells at defined temperatures.

3. Two Standard Biotools CyTOF Helios Mass Cytometers. Mass cytometry is a remarkable novel technology that enables the simultaneous detection of >50 metal-labeled antibodies and two DNA intercalators in a single panel.  Early in 2016 Standard Biotools released a new version of this instrumentation, the CyTOF Helios, which include marked improvements in performance, speed, easiness of operation (particularly in sample introduction) and the number of parameters (i.e., mass spec channels) that can be collected simultaneously, without the need for cross-beam compensation.  These improvements result in increased data quality and easiness of use compared to previous models. It allows an almost doubling of the acquisition events per second, 135 mass spec channels, increased sensitivity ( i.e., improved signal to noise ratios, now at 600,000 counts/pg Tb, resulting in even higher detection of low abundance targets), automated calibration, real-time bivariate plots, 7.2 Tb RAID, mirrored storage, etc

US patent 9,200,258: Multicellular Organotypic Model of Intestinal Mucosa, 2015.

• Inventors: Rosangela Mezghanni, Alessio Fasano, and Marcelo B Sztein