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Beyond Neutralizing Antibody Levels: The Epitope Specificity of Antibodies Induced by National Institutes of Health Monovalent Dengue Virus Vaccines
- Source :
- The Journal of Infectious Diseases
- Publication Year :
- 2019
- Publisher :
- Oxford University Press, 2019.
-
Abstract
- National Institutes of Health monovalent dengue vaccines and natural primary dengue virus infections elicit serotype-specific neutralizing antibodies that recognize similar epitopes.<br />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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 15376613 and 00221899
- Volume :
- 220
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- The Journal of Infectious Diseases
- Accession number :
- edsair.doi.dedup.....9bb8a8b78fe4c5b285788bbc82e33f8d