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Marcela F. Pasetti, PhD

Academic Title:

Professor

Primary Appointment:

Pediatrics

Secondary Appointment(s):

Microbiology and Immunology

Location:

HSFII S361

Phone (Primary):

(410) 706-5328

Fax:

(410) 706-6205

Education and Training

University of Buenos Aires, Orientation, Microbiology and Immunology, 1990

University of Buenos Aires, Ph.D., Immunology, 1994

Année Universitaire, Institute Pasteur, Diplome d’Immunologie Générale, 1994-1995

Postdoctoral Fellow, University of Maryland School of Medicine Center for Vaccine Development, 1996-2001

Biosketch

Dr. Pasetti researches vaccines and immunology to understand how protective immunity can be induced in animal models and in humans following infection and vaccination, and the mechanisms involved. Her primary areas of interests are pediatric vaccines, neonatal and infant immunology, and maternal immunization. She investigates novel vaccine strategies, antigen delivery systems, adjuvants, and immunization regimens for protection against pathogens that affect young children, as well as the influence of maternal immunity on infant immune responses to vaccines, and the impact of vaccine combination on long-term health and protection. Such knowledge is critical for successful pediatric immunization and to inform effective public health interventions.

Dr. Pasetti is particularly interested in vaccines that include live attenuated Salmonella and Shigella (alone or encoding foreign antigens), protein subunit vaccines, and polysaccharide conjugates. She is working in a new concept for a broadly protective pediatric vaccine against Salmonella, Shigella, and Yersinia based on conserved Type III secretion proteins, evaluating immunogenicity and protective efficacy in  adult, neonatal, and maternal-infant animal models.

Research/Clinical Keywords

Immunology, vaccines, immune responses, neonatal immunity, maternal-infant immunization, vaccine development, mucosal immunology, adjuvant, vaccine delivery systems.

Highlighted Publications

Levine MM, Pasetti MF. Serological monitoring is key to sustain progress of the maternal and neonatal tetanus elimination initiative. Clin Vaccine Immunol. 2016 Jul 5;23(7):532-4.

Tapia MD, Sow SO, Tamboura B, Tégueté I, Pasetti MF, Kodio M, Onwuchekwa U, Tennant SM, Blackwelder WC, Coulibaly F, Traoré A, Keita AM, Haidara FC, Diallo F2, Doumbia M, Sanogo D, DeMatt E, Schluterman NH, Buchwald A, Kotloff KL, Chen WH, Orenstein EW, Orenstein LA, Villanueva J, Bresee J, Treanor J, Levine MM. Maternal immunisation with trivalent inactivated influenza vaccine for prevention of influenza in infants in Mali: A prospective, active-controlled, observer-blind, randomised phase 4 trial. Lancet Infect Dis. 2016 Sep; 16(9):1026-35.

Mohan VK, Varanasi V, Singh A, Pasetti MF, Levine MM, Venkatesan R, Ella KM. Safety and immunogenicity of a Vi polysaccharide-tetanus toxoid conjugate vaccine (Typbar-TCV) in healthy infants, children, and adults in typhoid endemic areas: a multicenter, 2-cohort, open-label, double-blind, randomized controlled phase 3 study. Clin infect Dis. 2015 Aug 1;61(3):393-402.

Heine SJ, Diaz-McNair J, Andar AU, Drachenberg CB, van de Verg L, Walker R, Picking WL, Pasetti MF. Intradermal delivery of Shigella IpaB and IpaD Type III secretion proteins: kinetics of cell recruitment and antigen uptake, mucosal and systemic immunity and protection across serotypes. J Immunol. 2014 Feb 15;192(4):1630-40.

Muhsen K, Pasetti MF, Reymann MK, Graham DY, Levine MM. Helicobacter pylori infection affects immune responses following vaccination of typhoid-naive U.S. adults with attenuated Salmonella typhi oral vaccine CVD 908-htrA. J infect Dis. 2014 May1; 209(9):1452-8.

Additional Publication Citations

Heine SJ, Diaz-McNair J, Martinez-Becerra F, Choudhari S, Clements JD, Picking WL, Pasetti MF. Evaluation of immunogenicity and protective efficacy of orally delivered Shigella type III secretion system proteins IpaB and IpaD . Vaccine. 2013 Jun 19;31(28):2919-29.

Martinez-Becerra F, Kismann J, McNair J, Pasetti MF*, Picking, WL*. Broadly protective Shigella vaccine based on Type III secretion apparatus proteins. Infect Immun. 2012 Mar 80(3):1222-31. *shared senior/corresponding authors.

Ramirez K, Ditamo Y, Rodriguez L, Picking WL, van Roosmalen ML, Leenhouts K, Pasetti MF. Neonatal mucosal immunization with a non-living, non-genetically modified L. lactis vaccine carrier induces systemic and local Th1-type immunity and protects against lethal bacterial infection. Mucosal Immunol. 2010 Mar;3(2):159-71.

Pasetti MF, Ramirez K., Resendiz-Albor A., Ulmer J, Barry EM, Levine MM. Sindbis-virus measles Sindbis virus-based measles DNA vaccines protect cotton rats against respiratory measles; relevance of antibodies, mucosal and systemic antibody secreting cells, memory B cells and Th1-type cytokines as correlates of immunity. J Virol. 2009 Mar;83(6):2789-94.

Ramirez K, Capozzo AV, Lloyd SA, Sztein MB, Nataro JP, Pasetti MF. Mucosally delivered Salmonella Typhi expressing the Yersinia pestis F1 antigen elicits mucosal and systemic immunity early in life and primes the neonatal immune system for a vigorous anamnestic response to parenteral F1 boost. J Immunol. 2009 Jan 15;182(2):1211-22.

Pasetti MF, Resendiz-Albor A, Ramirez K, Stout R, Papania M, Adams RJ, Polack FP, Ward BJ, Burt D, Chabot S, Ulmer J, Barry EM, Levine MM. Heterologous prime-boost strategy to immunize very young infants against measles: Preclinical studies in rhesus macaques. Clin Pharmacol Ther. 2007 Dec;82(6):672-85.

Simon J, Pasetti MF, Viret JF, Munoz A, Lagos R, Levine MM, Campbell JD. A clinical study to assess the safety and immunogenicity of attenuated measles vaccine administered intranasally to healthy adults. Human Vaccines. 2007 Mar1;3(2):54-58.

Capozzo VE, Ramírez C, Polo JM, Ulmer J, Barry EM, Levine MM, Pasetti MF. Neonatal immunization with a Sindbis-virus DNA measles vaccine induce adult-like neutralizing antibodies and cell-mediated immunity in the presence of maternal antibodies. J Immunol. 2006 May 1;176(9):5671-81.

Tapia MD, Pasetti MF, Cuberos L, Sow SO, Doumbia MN, Bagayogo M, Kotloff KL, Levine MM. Measurement of tetanus antitoxin in oral fluid: A tool to conduct serosurveys. J Ped Infect Dis. 2006 Sep;25(9):819-25.

Research Interests

Two recent National Institutes of Health (NIH)-funded projects involve the study of mechanisms by which maternal immunity prevents shigellosis in young infants and the establishment and validation of serological assays that can predict efficacy of Shigella vaccine candidates in humans.

Dr. Pasetti is also interested in mucosal immunology. She has established an in vitro immune enteroid model system consisting of human primary gut epithelial cell monolayers and functionally integrated macrophages to study host-pathogen interactions and mucosal immunity. She is exploring mechanisms of translocation of vaccine-induced B. pertussis-specific IgG across the airways and IgG-mediated protection in a maternal-neonatal mouse model using FcRn-KO and hFcRn transgenic strains.

In addition to directing a thriving basic research program, Dr. Pasetti serves as Chief of the Applied Immunology Section at the Center for Vaccine Development (CVD). The Applied Immunology Lab performs a variety of immunological assays under a quality program to measure immune responses to vaccines during human clinical studies. Dr. Pasetti develops, refines, standardizes, and validates immunological methods for the purpose of assessing immune responses during infection and vaccination.

 

Grants and Contracts

Marcela F. Pasetti, Ph.D. (PI)
1R01AI117734-01
04/01/15-03/31/20
National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID)
Vaccines and Maternally Acquired Immunity to Prevent Shigellosis in Children

Marcela F. Pasetti, Ph.D. (PI)
1R01AI125841
04/22/16-0/21/21
NIH/NIAID
Serological Assays to Predict Shigella Vaccine Efficacy

Marcela F. Pasetti, Ph.D. (PI)
R21AI122248-01
12/15/15-11/14/17
NIH/NIAID
Role of Maternal and Infant Vaccine-induced IgG in Protection Against Pertussis

Marcela F. Pasetti, Ph.D. (PI)
R01AI 089519
06/07/10-05/30/17
NIH/NIAID
L. Lactis-based Vaccine for Children with Broad Spectrum for Enteric Pathogens

James Kaper, Ph.D. (PI)
Marcela F. Pasetti, Ph.D. (Immunology Core PI)
P01 AI 125181
07/01/16-06/30/21
NIH/NIAID
Pathogenesis of E. coli and Shigella in Hman Enteroid Models

Marcela F. Pasetti, Ph.D. (Task Area D PI)
HHSN272201300022I
12/01/2014-12/31/18
NIH/NIAID
Serological Evaluation of P. falciparum CSP Antibodies

  • This Vaccine Testing Evaluation Units (VETU) Task Oder is to provide lab/serology support for objectives of protocol 13-0088.

Marcela F. Pasetti, Ph.D. (Task Area D PI)
HHSN272201300022I
8/01/15-12/31/17
NIH/NIAID
Immunogenicity of Double Mutant Heat-Labile Toxin (dmLT) from

Marcela F. Pasetti, Ph.D. (PI)
06/26/13-6/30/17
PATH - Enteric Vaccine Initiative (EVI)
Immunological evaluation of ETEC vaccine candidate dmLT

Marcela F. Pasetti, Ph.D. (PI)
11/03/14-10/30/16
Bill & Melinda Gates Foundation
Grand Challenge Explorations Round 13
Pediatric Immune Enteroid Model of Gut Enteropathy

Marcela F. Pasetti, Ph.D. (PI)
8/22/14-8/30/2017
Immuron Ltd.
Immunologic Characterization of Bovine Colostrum

Marcela F. Pasetti, Ph.D. (PI)
06/01/14-2/28/17
Johns Hopkins University-subaward to the Bill & Melinda Gates Foundation
Immune Markers for Vaccine Preventable Diseases

Marcela F. Pasetti, Ph.D. (PI)
12/20/15-12/20/16
Vaxart, Inc.
Norwalk HAI Serological Measurements

Myron M. Levine, M.D., D.T.P.H. (PI)
Marcela F. Pasetti, Ph.D. (Co-PI)
08/01/15-03/31/17
Bill & Melinda Gates Foundation/JSI Washington and JSI Logistic Services
Universal Immunization Project (Ethiopia)

Myron M. Levine, M.D., D.T.P.H. (PI)
Marcela F. Pasetti, Ph.D. (Co-PI)
11/01/12-10/31/16
Bill & Melinda Gates Foundation
A point-of-care rapid assessment tool to detect protective levels of vaccine-related antibodies in oral (crevicular) fluid of infants, toddlers and older subjects

Raphael Simon, Ph.D. (PI)
Marcela F. Pasetti, Ph.D. (Co-Investigator)
R01AI110627-01
09/01/14-8/30/18
NIH/NIAID
Exploration of Protective Immunity Induced by Salmonella COPS: FLIC Conjugates

Karen L. Kotloff, M.D. (PI)
Marcela F. Pasetti, Ph.D. (Co-Investigator)
HHSN272201300022I
09/06/13-09/15/23
NIH/NIAID
Vaccine and Treatment Evaluation Unit (VTEU)

Myron M. Levine, M.D., D.T.P.H. (PI)
Marcela F. Pasetti, Ph.D. (Co-Investigator)
U19 AI09776
09/01/14-08/29/18
NIH/NIAID
Immunoprophylactic Strategies to Control Emerging Enteric Infections

Lab Techniques and Equipment

  • Meso Scale Direct Instrumentation for cytokine assays
  • EVOS XL Imaging systems (inverted light microscope)
  • EVOS FL Imaging systems (fluorescent microscope)
  • Analytical Balances
  • Thermal Cyclers
  • Gel Electrophoresis Instrumentation
  • Refrigerated Centrifuges
  • Refrigerated Micro-centrifuges
  • Incubator-Shakers
  • Luminometer
  • Spectrophotometer
  • Carbon Dioxide Incubators
  • Particle Counter
  • Bead Baths/Water Baths
  • Plate Shakers
  • pH Meters
  • Refrigerated Super-speed Centrifuge
  • Mini Bead-beater
  • GUAVA-mini flow cytometer
  • Biological Safety Cabinets
  • Chemical Fume Hoods

Laboratory Methods

  • Enzyme-Linked Immunosorbent Assay (ELISA)
  • Antibody Secreting Cells (ASC)
  • PBMC processing
  • Antibody Functional Assays (plaque reduction neutralization, toxin neutralization, serum bactericidal, opsonophagocytosis, inhibition of motility, microagglutination, hemagglutination inhibition)
  • Dry blood spot assays
  • Determination of Lewis secretor status
  • Cell and Tissue Culture
  • Virus and Bacteria Cultivation
  • Specimen Processing 
  • Development, Optimization and Qualification of Immunological Assays
  • Cord Blood Processing and Cell Isolation
  • Human Enteroid Treatment and Infection
  • Multi-array cytokine, chemokines, biomarker measurement
  • Western Blotting
  • Real-Time Polymerase Chain Reaction (RT-PCR)
  • Murine Challenge and Vaccination of Small Animal Models