Leah C. Katzelnick, Ph.D., MPH

Leah C. Katzelnick, Ph.D., MPH

Credit: NIAID
Chief, Viral Epidemiology and Immunity Unit

Major Areas of Research

  • Immunologically complex emerging and reemerging viral diseases, including dengue and Zika
  • Host immunologic correlates of enduring protection and disease
  • Antigenic and genetic viral evolution
  • Virus transmission dynamics

Biography

Dr. Leah Katzelnick pursued a Ph.D. studying antigenic variation among dengue viruses at the University of Cambridge and the National Institutes of Health as an NIH OxCam Scholar and Gates Cambridge Scholar. After receiving her Ph.D. in 2016, she conducted her postdoctoral work at the University of California, Berkeley and University of Florida on determinants of dengue and Zika disease, spending a year in Ecuador and Nicaragua to work closely with research teams conducting longitudinal cohort studies. In September of 2020, Leah became an Earl Stadtman tenure-track investigator and NIH Distinguished Scholar in the Laboratory of Infectious Diseases in NIAID. She is Chief of the new Viral Epidemiology and Immunity Unit.

Program Description

Background

Mosquito-borne flaviviruses infect hundreds of millions of people globally each year and cause a spectrum of life-threatening diseases, including hemorrhagic fevers, encephalitis, and severe congenital abnormalities. There are still no licensed, broadly protective vaccines against two of the most important flaviviruses: dengue virus and Zika virus. Dengue viruses 1-4 are challenging vaccine targets because sub-protective vaccines can increase risk of Dengue Hemorrhagic Fever/Dengue Shock Syndrome, the disease dengue vaccines are designed to prevent. The only licensed dengue vaccine to date significantly increases risk of severe dengue disease in those without a prior dengue virus exposure. Zika viruses emerged across the Americas in 2014-2017, causing major pandemics and congenital Zika syndrome, making development of a Zika vaccine a high priority.

Zika DENV Image

Prior Zika virus infection increases the probability of future symptomatic dengue virus infection (Katzelnick et al. Science 2020).

Credit
NIAID

Description

 The Viral Epidemiology and Immunity Unit (VEIU) uses a multidisciplinary approach to investigate immunological protection against and susceptibility to emerging and re-emerging viral diseases with the goal of informing how vaccines can be effectively and safely licensed and introduced through vaccination programs. Our work focuses on immunologically complex diseases caused by flaviviruses, including dengue and Zika viruses, as well as coronaviruses. We collaborate with research teams to study determinants of disease in longitudinal cohort and vaccine studies in Nicaragua, Sri Lanka, Thailand, Ecuador, the Philippines, and other sites. To address questions about virus antigenicity, host protective immunity, and population-level viral transmission dynamics, we use biologically relevant immunological assays and diverse computational and epidemiological methods to measure and evaluate the role of immunity in protection against disease in human cohort studies.

 Dengue Hemorrhagic Fever

Intermediate levels of preexisting anti-dengue virus antibodies increase risk of Dengue Hemorrhagic Fever/Dengue Shock Syndrome (Katzelnick et al. Science 2017).

Credit
NIAID

Key findings from previous research:

  • Pre-infection anti-dengue virus binding antibodies at concentrations within a 'danger zone' are associated with significantly increased risk of severe dengue disease, providing evidence from a large human study for antibody-dependent enhancement (Katzelnick et al., Science 2017).
  • Like a single prior dengue virus infection, one prior Zika virus infection increases future risk of severe dengue disease; further, pre-existing anti-flavivirus immunity differentially modulates future disease caused by different dengue virus serotypes (Katzelnick et al., Science 2020).  
  • Diverse dengue virus strains only loosely cluster antigenically by serotype and many strains are as similar antigenically to strains of a different serotype as to some strains of the same serotype (Katzelnick et al., Science 2015).
  • In a cohort study in Nicaragua, dramatic change in dengue virus transmission intensity over a 20-year period resulted in the age of seroconversion dropping from within to outside the recommended range specified by the World Health Organization for dengue vaccination (Katzelnick, Ben-Shachar et al., PNAS 2018).

DENV Antigenic Map

A subset of dengue viruses of each serotype are as close to viruses of another type as to some viruses of their own type (Katzelnick et al. Science 2015).

Credit
NIAID

Basic science and translational research objectives

The VEIU aims to identify drivers of antiviral immunity in population studies to inform basic science, vaccine design, and other public health and preventative measures. Specifically, we will study quaternary ‘super-antibodies', which bind epitopes across viral envelope proteins, and test whether these antibodies are mechanistic immune correlates of protection against dengue and other viral diseases. We will also characterize virus-specific neutralizing antibodies, which target variable viral epitopes that can evolve away from existing immunity. Overall, we aim to identify correlates of natural and vaccine protection and antibody-dependent enhancement in order to develop better next generation vaccines, extend the longevity of vaccine-induced immunity, and characterize how vaccines may affect viral evolution and transmission.

Research Group

Leah Katzelnick Research Group Image

From Left to Right: Ana Coello Escoto, Fernando Echegaray

Credit
NIAID

Ana Coello Escoto, Biologist and Lab Manager

Fernando Echegaray, Postbac IRTA

Selected Publications

Visit PubMed for a complete publication listing.

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