Sivaram Gunisetty1, Kaustuv Nayak2, Ramesh Chandra Rai2, Yadya Chawla2, Elluri Seetharami Reddy2, Charu Aggarwal2, Deepti Maheshwari2, Harekrushna Panda2, Nasim Akhtar Ansari2, Prabhat Singh2, Manpreet Kaur2, Kritika Dixit2, Pragati Sharma2, Priya Bhatnagar2, Lalita Priyamvada3, Siddhartha Kumar Bhaumik3, Syed Fazil Ahamed4, Rosario Vivek5, Pratima Ray6, Anita Shet7, Poonam Coshic8, Rakesh Lodha9, Sushil Kumar Kabra9, Dil Afroze10, Adfar Yousuf10, Rafi Ahmed11, Kaja Murali-Krishna12, Anmol Chandele13. 1. ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India; Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA, USA; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, 30322, USA. 2. ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India. 3. Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA, USA. 4. Division of Infectious Diseases, St. John's Research Institute, St. John's National Academy of Health Sciences, Koramangala, Bangalore, 560034, India; The University of Trans-Disciplinary Health Sciences & Technology, Bangalore, 560064, Karnataka, India. 5. Division of Infectious Diseases, St. John's Research Institute, St. John's National Academy of Health Sciences, Koramangala, Bangalore, 560034, India. 6. Department of Biotechnology, School of Clinical and Life Sciences, Jamia Hamdard, Mehrauli-Bardarpur Road, New Delhi, 110062, India. 7. Division of Infectious Diseases, St. John's Research Institute, St. John's National Academy of Health Sciences, Koramangala, Bangalore, 560034, India; International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, 415 N Washington St, Baltimore, 21231, USA. 8. Department of Transfusion Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India. 9. Division of Pediatric Pulmonology and Intensive Care, Department of Pediatrics, AIIMS, New Delhi, India. 10. Immunology & Molecular Medicine, Sher-i-Kashmir Institute of Medical Sciences-Srinagar, Jammu and Kashmir, 190011, India. 11. Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, 30322, USA; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, 30322, USA. 12. ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India; Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA, USA; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, 30322, USA. Electronic address: murali.kaja@emory.edu. 13. ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India. Electronic address: chandeleanmol@gmail.com.
Abstract
BACKGROUND: The Indian population is facing highest dengue burden worldwide supporting an urgent need for vaccines. For vaccine introduction, evaluation and interpretation it is important to gain a critical understanding of immune memory induced by natural exposure. However, immune memory to dengue remains poorly characterized in this region. METHODS: We enumerated levels of dengue specific memory B cells (MBC), neutralizing (NT) and binding antibodies in healthy adults (n=70) from New Delhi. RESULTS: NT-antibodies, binding antibodies and MBC were detectable in 86%, 86.56% and 81.63% of the subjects respectively. Among the neutralizing positive subjects, 58%, 27%, 5% and 10% neutralized all four, any three, any two and any one dengue serotypes respectively. The presence of the neutralizing antibodies was associated with the presence of the MBC and binding antibodies. However, a massive interindividual variation was observed in the levels of the neutralizing antibodies (range, <1:50-1:30,264), binding antibodies (range, 1:3,000-1:134,000,) as well as the MBC (range=0.006%-5.05%). CONCLUSION: These results indicate that a vast majority of the adults are immune to multiple dengue serotypes and show massive interindividual variation in neutralizing/binding antibodies and MBCs - emphasizing the importance of monitoring multiple parameters of immune memory in order to properly plan, evaluate and interpret dengue vaccines.
BACKGROUND: The Indian population is facing highest dengue burden worldwide supporting an urgent need for vaccines. For vaccine introduction, evaluation and interpretation it is important to gain a critical understanding of immune memory induced by natural exposure. However, immune memory to dengue remains poorly characterized in this region. METHODS: We enumerated levels of dengue specific memory B cells (MBC), neutralizing (NT) and binding antibodies in healthy adults (n=70) from New Delhi. RESULTS: NT-antibodies, binding antibodies and MBC were detectable in 86%, 86.56% and 81.63% of the subjects respectively. Among the neutralizing positive subjects, 58%, 27%, 5% and 10% neutralized all four, any three, any two and any one dengue serotypes respectively. The presence of the neutralizing antibodies was associated with the presence of the MBC and binding antibodies. However, a massive interindividual variation was observed in the levels of the neutralizing antibodies (range, <1:50-1:30,264), binding antibodies (range, 1:3,000-1:134,000,) as well as the MBC (range=0.006%-5.05%). CONCLUSION: These results indicate that a vast majority of the adults are immune to multiple dengue serotypes and show massive interindividual variation in neutralizing/binding antibodies and MBCs - emphasizing the importance of monitoring multiple parameters of immune memory in order to properly plan, evaluate and interpret dengue vaccines.