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Stimulation of B Cell Immunity in Flavivirus-Naïve Individuals by the Tetravalent Live Attenuated Dengue Vaccine TV003

39 Pages Posted: 21 Apr 2020 Publication Status: Published

See all articles by Huy A. Tu

Huy A. Tu

University of Vermont - Department of Microbiology and Molecular Genetics

Usha K. Nivarthi

University of North Carolina (UNC) at Chapel Hill - Department of Microbiology and Immunology

Matthew J. Delacruz

University of North Carolina (UNC) at Chapel Hill - Department of Microbiology and Immunology

Kristen K. Pierce

University of Vermont - Department of Microbiology and Molecular Genetics

Stephen S. Whitehead

National Institutes of Health - Laboratory of Viral Diseases

Jonathan E. Boyson

University of Vermont

Jason W. Botten

University of Vermont - Department of Microbiology and Molecular Genetics

Beth D. Kirkpatrick

University of Vermont - Department of Microbiology and Molecular Genetics

Anna Durbin

Johns Hopkins University - Department of International Health

Aravinda M. deSilva

University of North Carolina School of Medicine - Department of Microbiology and Immunology

Sean Diehl

University of Vermont Larner College of Medicine - Microbiology and Molecular Genetics

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Abstract

The tetravalent live attenuated dengue vaccine candidate TV003 induces neutralizing antibodies against all four dengue virus serotypes (DENV1-4), and protects against experimental DENV2 challenge in humans. Protection occurred with or without a secondary post-challenge rise in DENV2-specific neutralizing antibodies. Here we combined high resolution temporal sampling and analysis of antigen-specific responses after vaccination and challenge to determine the cellular underpinnings of the B cell response in relation to vaccine viremia and serum antibodies. TV003 vaccine-related viremia was associated with an acute plasmablast response that correlated with the development of serum neutralizing antibodies. At six-months following immunization, subjects had developed DENV2-specific memory B cells including serotype-specific and multi-valent responders. DENV2 challenge of vaccinees did not induce a post-challenge plasmablast response, though stronger and earlier post-vaccine plasmablast responses were associated with sterile humoral protection from DENV2 challenge (i.e. a lack of DENV2 antibody boosting). Our findings demonstrate that TV003 vaccine triggers a durable B cell response containing plasmablasts and memory B cells which functionally link early vaccine viremia and the serum antibody responses.

Keywords: dengue, tetravalent vaccine, B cells, adaptive immunity

Suggested Citation

Tu, Huy A. and Nivarthi, Usha K. and Delacruz, Matthew J. and Pierce, Kristen K. and Whitehead, Stephen S. and Boyson, Jonathan E. and Botten, Jason W. and Kirkpatrick, Beth D. and Durbin, Anna and deSilva, Aravinda M. and Diehl, Sean, Stimulation of B Cell Immunity in Flavivirus-Naïve Individuals by the Tetravalent Live Attenuated Dengue Vaccine TV003. Available at SSRN: https://ssrn.com/abstract=3581774 or http://dx.doi.org/10.2139/ssrn.3581774
This version of the paper has not been formally peer reviewed.

Huy A. Tu

University of Vermont - Department of Microbiology and Molecular Genetics ( email )

United States

Usha K. Nivarthi

University of North Carolina (UNC) at Chapel Hill - Department of Microbiology and Immunology ( email )

Chapel Hill, NC
United States

Matthew J. Delacruz

University of North Carolina (UNC) at Chapel Hill - Department of Microbiology and Immunology ( email )

Chapel Hill, NC
United States

Kristen K. Pierce

University of Vermont - Department of Microbiology and Molecular Genetics

United States

Stephen S. Whitehead

National Institutes of Health - Laboratory of Viral Diseases

Bethesda, MD 20892-9806
United States

Jonathan E. Boyson

University of Vermont ( email )

212 Kalkin Hall
Burlington, VT 05405-0158
United States

Jason W. Botten

University of Vermont - Department of Microbiology and Molecular Genetics ( email )

United States

Beth D. Kirkpatrick

University of Vermont - Department of Microbiology and Molecular Genetics ( email )

United States

Anna Durbin

Johns Hopkins University - Department of International Health ( email )

Baltimore, MD 21205
United States

Aravinda M. DeSilva

University of North Carolina School of Medicine - Department of Microbiology and Immunology ( email )

Chapel Hill, NC
United States

Sean Diehl (Contact Author)

University of Vermont Larner College of Medicine - Microbiology and Molecular Genetics ( email )

95 Carrigan Ave
Burlington, VT 05405
United States

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