Sequential immunization induces strong and broad immunity against all four dengue virus serotypes
| Autor: | Jianzhu Chen, Hooi Linn Loo, Lan Hiong Wong, Eng Eong Ooi, Shubham Shrivastava, Jue Hou |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy Immunology chemical and pharmacologic phenomena Biology Dengue virus medicine.disease_cause lcsh:RC254-282 Article DNA vaccines Dengue fever DNA vaccination 03 medical and health sciences 0302 clinical medicine Immunity medicine Pharmacology (medical) Dengue vaccine Pharmacology biochemical phenomena metabolism and nutrition medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Virology Vaccination 030104 developmental biology Infectious Diseases Immunization 030220 oncology & carcinogenesis biology.protein bacteria Antibody lcsh:RC581-607 |
| Zdroj: | npj Vaccines, Vol 5, Iss 1, Pp 1-11 (2020) NPJ Vaccines |
| ISSN: | 2059-0105 |
| Popis: | A major challenge in dengue vaccine development is the need to induce immunity against four dengue (DENV) serotypes. Dengvaxia®, the only licensed dengue vaccine, consists of four variant dengue antigens, one for each serotype. Three doses of immunization with the tetravalent vaccine induced only suboptimal protection against DENV1 and DENV2. Furthermore, vaccination paradoxically and adversely primes dengue naïve subjects to more severe dengue. Here, we have tested whether sequential immunization induces stronger and broader immunity against four DENV serotypes than tetravalent-formulated immunization. Mice were immunized with four DNA plasmids, each encoding the pre-membrane and envelope from one DENV serotype, either sequentially or simultaneously. The sequential immunization induced significantly higher levels of interferon (IFN)γ- or tumor necrosis factor (TNF)α-expressing CD4+ and CD8+ T cells to both serotype-specific and conserved epitopes than tetravalent immunization. Moreover, sequential immunization induced higher levels of neutralizing antibodies to all four DENV serotypes than tetravalent vaccination. Consistently, sequential immunization resulted in more diversified immunoglobulin repertoire, including increased complementarity determining region 3 (CDR3) length and more robust germinal center reactions. These results show that sequential immunization offers a simple approach to potentially overcome the current challenges encountered with tetravalent-formulated dengue vaccines. |
| Databáze: | OpenAIRE |
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