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Immune Cell Phenotypes that Determine Disease Severity and Long-Term Neutralizing Antibody Titers after Natural Dengue Virus Infection

79 Pages Posted: 17 Apr 2020 Publication Status: Published

See all articles by Angeline Rouers

Angeline Rouers

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs

Melissa Chng

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Bernett Lee

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Menaka P. Rajapakse

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Kaval Kaur

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Ying Xiu Toh

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Durgalakshmi Sathiakumar

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Yee Sin Leo

National Centre for Infectious Diseases

Kalpit Vora

Merck & Co., Inc.

Danilo Casimiro

Merck & Co., Inc.

Bing Lim

Merck & Co., Inc.

Lisa Tucker-Kellogg

Duke-NUS Graduate Medical School Singapore

Laura Rivino

Duke-NUS Medical School - Emerging Infectious Diseases Programme

Evan W. Newell

Fred Hutchinson Cancer Research Center - Vaccine and Infectious Disease Division; Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Katja Fink

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

More...

Abstract

Prior immunological exposure to dengue virus can be both protective and disease-enhancing during subsequent infections with different dengue virus serotypes. We provide here for the first time a systematic, longitudinal analysis of B cell, T cell, and antibody responses in the same patients. Antibody responses as well as T and B cell activation differentiated primary versus secondary responses. Disease severity was associated with lower frequencies of activated, terminally differentiated T cells and higher percentages of effector memory CD4 T cells. Patients with more severe disease tended to have higher percentages of plasmablasts. This did not translate into long-term antibody titers, since neutralizing titers after six months were associated with percentages of specific memory B cells but not with acute plasmablast activation. Overall, our unbiased analysis reveals novel and unexpected associations between cellular profiles and disease severity,opening new opportunities to study immunopathology in dengue disease and potential predictive value of these parameters.

Keywords: Dengue, T cell, B cell, Longitudinal, Disease Severity, Antibodies, Correlates of Protection

Suggested Citation

Rouers, Angeline and Chng, Melissa and Lee, Bernett and Rajapakse, Menaka P. and Kaur, Kaval and Toh, Ying Xiu and Sathiakumar, Durgalakshmi and Leo, Yee Sin and Vora, Kalpit and Casimiro, Danilo and Lim, Bing and Tucker-Kellogg, Lisa and Rivino, Laura and Newell, Evan W. and Fink, Katja, Immune Cell Phenotypes that Determine Disease Severity and Long-Term Neutralizing Antibody Titers after Natural Dengue Virus Infection. Available at SSRN: https://ssrn.com/abstract=3565008 or http://dx.doi.org/10.2139/ssrn.3565008
This version of the paper has not been formally peer reviewed.

Angeline Rouers

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs ( email )

Singapore

Melissa Chng

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN) ( email )

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Bernett Lee

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN) ( email )

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Menaka P. Rajapakse

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN) ( email )

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Kaval Kaur

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN) ( email )

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Ying Xiu Toh

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN) ( email )

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Durgalakshmi Sathiakumar

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN) ( email )

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Yee Sin Leo

National Centre for Infectious Diseases ( email )

Singapore

Kalpit Vora

Merck & Co., Inc. ( email )

United States

Danilo Casimiro

Merck & Co., Inc. ( email )

United States

Bing Lim

Merck & Co., Inc. ( email )

United States

Lisa Tucker-Kellogg

Duke-NUS Graduate Medical School Singapore

Singapore
Singapore

Laura Rivino

Duke-NUS Medical School - Emerging Infectious Diseases Programme

Singapore

Evan W. Newell

Fred Hutchinson Cancer Research Center - Vaccine and Infectious Disease Division

Seattle, WA 98109-1024
United States

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Katja Fink (Contact Author)

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN) ( email )

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

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