Beyond Neutralizing Antibody Levels: The Epitope Specificity of Antibodies Induced by National Institutes of Health Monovalent Dengue Virus Vaccines
| Autor: | Bhumi Patel, Stephen S. Whitehead, Boyd Yount, Anna P. Durbin, Douglas G. Widman, Aravinda M. de Silva, Usha K. Nivarthi, Jesica Swanstrom, Ralph S. Baric, Matthew J. Delacruz |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Serotype viruses Dengue Vaccines Dengue virus medicine.disease_cause Antibodies Viral Serogroup Vaccines Attenuated Epitope Dengue 03 medical and health sciences Major Articles and Brief Reports Epitopes 0302 clinical medicine flavivirus Viral Envelope Proteins dengue vaccine medicine Immunology and Allergy Humans 030212 general & internal medicine Amino Acid Sequence Neutralizing antibody Dengue vaccine Vaccines live attenuated vaccine Attenuated vaccine biology Vaccination neutralizing antibody Dengue Virus biology.organism_classification Virology Antibodies Neutralizing United States 3. Good health Flavivirus 030104 developmental biology Infectious Diseases National Institutes of Health (U.S.) biology.protein Epitope Mapping |
| Zdroj: | The Journal of Infectious Diseases |
| ISSN: | 1537-6613 0022-1899 |
| Popis: | National Institutes of Health monovalent dengue vaccines and natural primary dengue virus infections elicit serotype-specific neutralizing antibodies that recognize similar epitopes. Background Dengue virus is an emerging mosquito-borne flavivirus responsible for considerable morbidity and mortality worldwide. The Division of Intramural Research, National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (NIH) has developed live attenuated vaccines to each of the 4 serotypes of dengue virus (DENV1–4). While overall levels of DENV neutralizing antibodies (nAbs) in humans have been correlated with protection, these correlations vary depending on DENV serotype, prevaccination immunostatus, age, and study site. By combining both the level and molecular specificity of nAbs to each serotype, it may be possible to develop more robust correlates that predict long-term outcome. Methods Using depletions and recombinant chimeric epitope transplant DENVs, we evaluate the molecular specificity and mapped specific epitopes and antigenic regions targeted by vaccine-induced nAbs in volunteers who received the NIH monovalent vaccines against each DENV serotype. Results After monovalent vaccination, subjects developed high levels of nAbs that mainly targeted epitopes that are unique (type-specific) to each DENV serotype. The DENV1, 2, and 4 monovalent vaccines induced type-specific nAbs directed to quaternary structure envelope epitopes known to be targets of strongly neutralizing antibodies induced by wild-type DENV infections. Conclusions Our results reported here on the molecular specificity of NIH vaccine–induced antibodies enable new strategies, beyond the absolute levels of nAbs, for determining correlates and mechanisms of protective immunity. |
| Databáze: | OpenAIRE |
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