. 2017 Aug 24;35(36):4659-4669.

doi: 10.1016/j.vaccine.2017.07.045. Epub 2017 Jul 28.

Immune correlates of protection for dengue: State of the art and research agenda

Leah C Katzelnick¹, Eva Harris²; Participants in the Summit on Dengue Immune Correlates of Protection

Collaborators, Affiliations

Collaborators

Participants in the Summit on Dengue Immune Correlates of Protection:
Ralph Baric³, Beth-Ann Coller⁴, Josefina Coloma⁵, James E Crowe Jr⁶, Derek A T Cummings⁷, Hansi Dean⁸, Aravinda de Silva⁹, Michael S Diamond¹⁰, Anna Durbin¹¹, Neil Ferguson¹², Peter B Gilbert¹³, Aubree Gordon¹⁴, Duane J Gubler¹⁵, Bruno Guy¹⁶, M Elizabeth Halloran¹³, Scott Halstead¹⁷, Nicholas Jackson¹⁶, Richard Jarman¹⁸, Shee-Mei Lok¹⁹, Nelson L Michael²⁰, Eng Eong Ooi¹⁵, Athanasios Papadopoulos²¹, Stanley Plotkin²², Alexander R Precioso²³, Robert Reiner²⁴, Felix A Rey²⁵, Isabel Rodríguez-Barraquer²⁶, Alan Rothman²⁷, Alexander C Schmidt²⁸, Gavin Screaton²⁹, Alessandro Sette³⁰, Cameron Simmons³¹, Ashley L St John¹⁵, Wellington Sun³², Stephen Thomas³³, Joseph Torresi³⁴, John S Tsang³⁵, Kirsten Vannice³⁶, Stephen Whitehead³⁷, Annelies Wilder-Smith³⁸, In Kyu Yoon³⁹

Affiliations

¹ Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA; Department of Biology, University of Florida, Gainesville, FL 32611, USA.
² Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA. Electronic address: eharris@berkeley.edu.
³ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7435, USA.
⁴ Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ, USA.
⁵ Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA.
⁶ Departments of Pediatrics and Pathology, Microbiology, and Immunology, Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN, USA.
⁷ Department of Biology and Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
⁸ Takeda Pharmaceutical Company Limited, Cambridge, MA 02139, USA.
⁹ Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
¹⁰ Departments of Medicine, Molecular Microbiology, and Pathology and Immunology, The Andrew M. and Jane M. Bursky Center for Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO 63110, USA.
¹¹ Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
¹² MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
¹³ Vaccine and Infectious Disease Institute, Hutchinson Research Center, Seattle, WA 98109, USA; Department of Biostatistics, University of Washington, Seattle, WA 98109, USA.
¹⁴ Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
¹⁵ Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857, Singapore.
¹⁶ Research & Development, Sanofi Pasteur, 69007 Lyon, France.
¹⁷ Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
¹⁸ Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
¹⁹ Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857, Singapore; Centre for BioImaging Sciences, National University of Singapore, Singapore 117557, Singapore.
²⁰ US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
²¹ Global Clinical Sciences, Sanofi Pasteur, Marcy l'Etoile 69280, France.
²² Vaxconsult, Doylestown, PA, USA; University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
²³ Clinical Trials and Pharmacovigilance Division, Instituto Butantan, São Paulo, Brazil; Pediatrics Department, School of Medicine of University of São Paulo, São Paulo, Brazil.
²⁴ Department of Epidemiology and Biostatistics, Indiana University Bloomington School of Public Health, Bloomington, IN, USA.
²⁵ Structural Virology Unit, Department of Virology, Institut Pasteur, Paris 75724, France.
²⁶ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; Department of Medicine, University of California, San Francisco, CA, USA.
²⁷ Institute for Immunology and Informatics, Department of Cell and Molecular Biology, University of Rhode Island, Providence, RI 02903, USA.
²⁸ Vaccine Discovery and Development, GSK Vaccines, US R&D Center, Rockville, MD 20850, USA.
²⁹ Division of Immunology and Inflammation, Department of Medicine, Hammersmith Campus, Imperial College London, London, United Kingdom.
³⁰ La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
³¹ Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam; Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; Department of Microbiology and Immunology, University of Melbourne, Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.
³² Division of Vaccines and Related Products Applications, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
³³ Department of Medicine, Upstate Medical University of New York, Syracuse, NY 13210, USA.
³⁴ Department of Microbiology and Immunology, University of Melbourne, Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.
³⁵ Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Trans-NIH Center for Human Immunology, National Institutes of Health, Bethesda, MD 20892, USA.
³⁶ Initiative for Vaccine Research, World Health Organization, Geneva, Switzerland.
³⁷ Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
³⁸ Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore; London School of Hygiene and Tropical Medicine, London, United Kingdom.
³⁹ Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; International Vaccine Institute, Seoul, South Korea.

PMID: 28757058
PMCID: PMC5924688
DOI: 10.1016/j.vaccine.2017.07.045

Immune correlates of protection for dengue: State of the art and research agenda

Leah C Katzelnick et al. Vaccine. 2017.

. 2017 Aug 24;35(36):4659-4669.

doi: 10.1016/j.vaccine.2017.07.045. Epub 2017 Jul 28.

Authors

Leah C Katzelnick¹, Eva Harris²; Participants in the Summit on Dengue Immune Correlates of Protection

Collaborators

Participants in the Summit on Dengue Immune Correlates of Protection:
Ralph Baric³, Beth-Ann Coller⁴, Josefina Coloma⁵, James E Crowe Jr⁶, Derek A T Cummings⁷, Hansi Dean⁸, Aravinda de Silva⁹, Michael S Diamond¹⁰, Anna Durbin¹¹, Neil Ferguson¹², Peter B Gilbert¹³, Aubree Gordon¹⁴, Duane J Gubler¹⁵, Bruno Guy¹⁶, M Elizabeth Halloran¹³, Scott Halstead¹⁷, Nicholas Jackson¹⁶, Richard Jarman¹⁸, Shee-Mei Lok¹⁹, Nelson L Michael²⁰, Eng Eong Ooi¹⁵, Athanasios Papadopoulos²¹, Stanley Plotkin²², Alexander R Precioso²³, Robert Reiner²⁴, Felix A Rey²⁵, Isabel Rodríguez-Barraquer²⁶, Alan Rothman²⁷, Alexander C Schmidt²⁸, Gavin Screaton²⁹, Alessandro Sette³⁰, Cameron Simmons³¹, Ashley L St John¹⁵, Wellington Sun³², Stephen Thomas³³, Joseph Torresi³⁴, John S Tsang³⁵, Kirsten Vannice³⁶, Stephen Whitehead³⁷, Annelies Wilder-Smith³⁸, In Kyu Yoon³⁹

Affiliations

¹ Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA; Department of Biology, University of Florida, Gainesville, FL 32611, USA.
² Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA. Electronic address: eharris@berkeley.edu.
³ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7435, USA.
⁴ Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ, USA.
⁵ Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA.
⁶ Departments of Pediatrics and Pathology, Microbiology, and Immunology, Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN, USA.
⁷ Department of Biology and Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
⁸ Takeda Pharmaceutical Company Limited, Cambridge, MA 02139, USA.
⁹ Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
¹⁰ Departments of Medicine, Molecular Microbiology, and Pathology and Immunology, The Andrew M. and Jane M. Bursky Center for Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO 63110, USA.
¹¹ Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
¹² MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
¹³ Vaccine and Infectious Disease Institute, Hutchinson Research Center, Seattle, WA 98109, USA; Department of Biostatistics, University of Washington, Seattle, WA 98109, USA.
¹⁴ Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
¹⁵ Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857, Singapore.
¹⁶ Research & Development, Sanofi Pasteur, 69007 Lyon, France.
¹⁷ Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
¹⁸ Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
¹⁹ Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857, Singapore; Centre for BioImaging Sciences, National University of Singapore, Singapore 117557, Singapore.
²⁰ US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
²¹ Global Clinical Sciences, Sanofi Pasteur, Marcy l'Etoile 69280, France.
²² Vaxconsult, Doylestown, PA, USA; University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
²³ Clinical Trials and Pharmacovigilance Division, Instituto Butantan, São Paulo, Brazil; Pediatrics Department, School of Medicine of University of São Paulo, São Paulo, Brazil.
²⁴ Department of Epidemiology and Biostatistics, Indiana University Bloomington School of Public Health, Bloomington, IN, USA.
²⁵ Structural Virology Unit, Department of Virology, Institut Pasteur, Paris 75724, France.
²⁶ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; Department of Medicine, University of California, San Francisco, CA, USA.
²⁷ Institute for Immunology and Informatics, Department of Cell and Molecular Biology, University of Rhode Island, Providence, RI 02903, USA.
²⁸ Vaccine Discovery and Development, GSK Vaccines, US R&D Center, Rockville, MD 20850, USA.
²⁹ Division of Immunology and Inflammation, Department of Medicine, Hammersmith Campus, Imperial College London, London, United Kingdom.
³⁰ La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
³¹ Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam; Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; Department of Microbiology and Immunology, University of Melbourne, Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.
³² Division of Vaccines and Related Products Applications, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
³³ Department of Medicine, Upstate Medical University of New York, Syracuse, NY 13210, USA.
³⁴ Department of Microbiology and Immunology, University of Melbourne, Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.
³⁵ Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Trans-NIH Center for Human Immunology, National Institutes of Health, Bethesda, MD 20892, USA.
³⁶ Initiative for Vaccine Research, World Health Organization, Geneva, Switzerland.
³⁷ Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
³⁸ Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore; London School of Hygiene and Tropical Medicine, London, United Kingdom.
³⁹ Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; International Vaccine Institute, Seoul, South Korea.

PMID: 28757058
PMCID: PMC5924688
DOI: 10.1016/j.vaccine.2017.07.045

Abstract

Dengue viruses (DENV1-4) are mosquito-borne flaviviruses estimated to cause up to ∼400 million infections and ∼100 million dengue cases each year. Factors that contribute to protection from and risk of dengue and severe dengue disease have been studied extensively but are still not fully understood. Results from Phase 3 vaccine efficacy trials have recently become available for one vaccine candidate, now licensed for use in several countries, and more Phase 2 and 3 studies of additional vaccine candidates are ongoing, making these issues all the more urgent and timely. At the "Summit on Dengue Immune Correlates of Protection", held in Annecy, France, on March 8-9, 2016, dengue experts from diverse fields came together to discuss the current understanding of the immune response to and protection from DENV infection and disease, identify key unanswered questions, discuss data on immune correlates and plans for comparison of results across assays/consortia, and propose a research agenda for investigation of dengue immune correlates, all in the context of both natural infection studies and vaccine trials.

Keywords: Dengue virus; Immune correlates of protection; Immune correlates of risk; Natural infection; Vaccine.

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Conflict of interest statement

Conflicts of Interest

The Partnership for Dengue Control has multiple operating partners, including Fondation Mérieux, Dengue Vaccine Initiative (DVI), National Institutes of Health (NIH), and Sabin Vaccine Institute, as well as funding partners, including Bill & Melinda Gates Foundation, Sanofi Pasteur, Takeda, Bayer, GSK, and bioMérieux. Ralph Baric has financial relationships with several dengue tetravalent virus vaccine manufacturers. Beth-Ann Coller is an employee, shareholder, and patent inventor for Merck & Co., Inc., Kenilworth, NJ, USA. James E. Crowe, Jr. is a consultant for Sanofi; is on the Scientific Advisory Boards of PaxVax, CompuVax, GigaGen, Meissa Vaccines, and Rensavir; and is a recipient of research grants from Moderna and Sanofi. Derek Cummings, Neil Ferguson, and Isabel Rodriguez-Barraquer advised Sanofi Pasteur Ltd., without payment, on modeling the potential impact of their dengue vaccine. Hansi Dean an employee of Takeda Pharmaceuticals Vaccine Business Unit. Aravinda de Silva has consulted for Takeda Vaccines, GSK and Merck Pharmaceuticals and is an inventor on patents related to dengue vaccines that have been filed by the University of North Carolina. Michael S. Diamond is a consultant for Inbios, Visterra, and Takeda Pharmaceuticals and on the Scientific Advisory Boards of Moderna and OvaGene. Peter B. Gilbert received a contract from Sanofi Pasteur to analyze data from its clinical trials. Duane J. Gubler is a patent holder on the Takeda dengue vaccine, has Investment in Takeda Pharmaceuticals, and has consulting activities to Sanofi, Takeda, and Merck on dengue. M. Elizabeth Halloran is in the Modelling Consortium with Sanofi, but did not receive payment and is involved in the development of the Phase IV evaluation of Dengvaxia in the Yucatan. Eva Harris served on the Scientific Advisory Board of Sanofi Pasteur during the Phase 3 vaccine trials, and her laboratory received research funds from Takeda Vaccines, Inc. to analyze samples from vaccine recipients. Nicholas Jackson, Bruno Guy, and Athanasios Papadopoulos are Sanofi Pasteur employees. Stanley Plotkin is a consultant to many manufacturers, including Sanofi Pasteur, manufacturer of a dengue vaccine. Alexander R. Precioso is the Director of the Clinical Trials and Pharmacovigilance Division and coordinator of the phase III Butantan dengue vaccine clinical trial for Instituto Butantan, a public owned Institution of the Government of Sao Paulo State, Brazil, which has a development and manufacturing program for an attenuated tetravalent dengue vaccine. Alan Rothman has served as a Consultant for Sanofi and Takeda. Alexander Schmidt is an employee of the GSK group of companies and holds shares in GSK. Gavin Screaton and Felix A. Rey are named inventors on a patent application by Imperial College and Institut Pasteur for EDE antibodies and epitope. Cameron Simmons is a principal investigator in the Eliminate Dengue program – this entity is evaluating a technology for arbovirus disease control that competes with dengue vaccines. Joseph Torresi has had speaker honoraria and consultancies with Sanofi Pasteur, GSK, and Bristol Myers Squibb and an unrestricted research grant with SanofiPasteur. Kirsten Vannice is a staff member of the World Health Organization. Leah Katzelnick, Josefina Coloma, Anna Durbin, Aubree Gordon, Scott Halstead, Richard Jarman, Shee-mei Lok, Nelson Michael, Robert Reiner, Alessandro Sette, Ashley St. John, Wellington Sun, Stephen Thomas, John Tsang, Stephen Whitehead, Annelies Wilder-Smith, and In Kyu Yoon do not report conflicts of interest.

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Immune correlates of protection for dengue: State of the art and research agenda

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Immune correlates of protection for dengue: State of the art and research agenda

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