Host-Pathogen Interactions and Structural Vaccinology Section
Established in 2018
Niraj Harish Tolia, Ph.D. (He/Him/His)
Chief, Host-Pathogen Interactions and Structural Vaccinology Section
Contact: For contact information, search the NIH Enterprise Directory.
Major Areas of Research
- Host-pathogen interactions: structure, function and mechanism
- Mechanisms of protective antibody neutralization
- Structural vaccinology for infectious diseases
The mission of the Host-Pathogen Interactions and Structural Vaccinology Section (HPISV) is to define molecular mechanisms required for infectious diseases pathogenesis, and to elucidate the fundamental phenomena necessary to develop potent and durable vaccines through structural vaccinology. We utilize protein design, structural biology, immunology, vaccinology, microbiology, and biophysics to examine proteins and protein complexes associated with pathogenesis.
Infectious diseases vaccines could be significantly improved by structure-guided design of immunogens, which enables more precise targeting of well-defined epitopes that elicit protective responses, while also limiting immune responses that are non-protective or interfering. Our group pursues vaccine development by conducting research in three areas: 1) host-pathogen interactions; 2) neutralizing antibodies; and 3) structural vaccinology for infectious diseases. Through structural, functional, and mechanistic studies, we define critical host-pathogen interactions and the mechanisms of protective antibody neutralization. These studies enable structure-guided antigen design and structural vaccinology for malaria and COVID-19 to develop potent and durable vaccines.
Ph.D., 2004, Cold Spring Harbor Laboratory School of Biological Sciences, NY
B.Sc., 1999, Imperial College, London
Dr. Tolia became the Chief of the Host-Pathogen Interactions and Structural Vaccinology section in the Laboratory of Malaria Immunology and Vaccinology in May 2018. He is a tenured Senior Investigator in the Division of Intramural Research, NIAID. He has pioneered the structural and biophysical studies of host-pathogen interactions, antibody neutralization and immunogen design for malaria, and has recently expanded his efforts to address pandemic viral diseases. A major goal is to define how processes required for pathogen survival are mediated and can be exploited to develop vaccines, therapeutics, and diagnostics. His laboratory uses the tools of protein design, structural biology, immunology, vaccinology, microbiology, and biophysics to develop potent and durable interventions for infectious diseases.
Dr. Tolia received his B.Sc from Imperial College, and his Ph.D. from the Cold Spring Harbor Laboratory School of Biological Sciences as a Leslie Quick Jr. Fellow. He began his independent career as an Assistant Professor of Molecular Microbiology, and of Biochemistry and Molecular Biophysics at Washington University in November 2007. He was the recipient of an Investigator in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund and his research was supported by grants from the National Institutes of Health, the Edward Mallinckrodt, Jr. Foundation, the American Heart Association, and the W.M. Keck Foundation.
Dickey TH, Ma R, Orr-Gonzalez S, Ouahes T, Patel P, McAleese H, Butler B, Eudy E, Eaton B, Murphy M, Kwan JL, Salinas ND, Holbrook MR, Lambert LE, Tolia NH. Design of a stabilized RBD enables potently neutralizing SARS-CoV-2 single-component nanoparticle vaccines. Cell Rep. 2023 Mar 6;42(3):112266.
Tang WK, Coelho CH, Miura K, Nguemwo Tentokam BC, Salinas ND, Narum DL, Healy SA, Sagara I, Long CA, Duffy PE, Tolia NH. A human antibody epitope map of Pfs230D1 derived from analysis of individuals vaccinated with a malaria transmission-blocking vaccine. Immunity. 2023 Feb 14;56(2):433-443.e5.
Patel PN, Dickey TH, Hopp CS, Diouf A, Tang WK, Long CA, Miura K, Crompton PD, Tolia NH. Neutralizing and interfering human antibodies define the structural and mechanistic basis for antigenic diversion. Nat Commun. 2022 Oct 6;13(1):5888.
Dickey TH, Tang WK, Butler B, Ouahes T, Orr-Gonzalez S, Salinas ND, Lambert LE, Tolia NH. Design of the SARS-CoV-2 RBD vaccine antigen improves neutralizing antibody response. Sci Adv. 2022 Sep 16;8(37):eabq8276.
Ma R, Lian T, Huang R, Renn JP, Petersen JD, Zimmerberg J, Duffy PE, Tolia NH. Structural basis for placental malaria mediated by Plasmodium falciparum VAR2CSA. Nat Microbiol. 2021 Mar;6(3):380-391.
Urusova D, Carias L, Huang Y, Nicolete VC, Popovici J, Roesch C, Salinas ND, Dechavanne S, Witkowski B, Ferreira MU, Adams JH, Gross ML, King CL, Tolia NH. Structural basis for neutralization of Plasmodium vivax by naturally acquired human antibodies that target DBP. Nat Microbiol. 2019 Sep;4(9):1486-1496.
The Host-Pathogen Interactions and Structural Vaccinology Section (HPISV) seeks to uncover the fundamental phenomena necessary to develop the next generation of vaccines through structural vaccinology. Structure-guided design of immunogens to elicit well-defined immune responses will likely lead to significant improvements in vaccine efficacy and durability.