Preclinical development of a dengue tetravalent recombinant subunit vaccine: Immunogenicity and protective efficacy in nonhuman primates

Highlights • Subunit DEN-80E protein was evaluated as monovalent and tetravalent formulations for immunogenicity and efficacy in non-human primates. • Monomeric and dimeric forms of DEN4-80E were found to be equally immunogenic/protective when formulated with ISCOMATRIX™ adjuvant. • Tetravalent DEN-...

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Bibliographic Details
Published in:Vaccine 2015-08, Vol.33 (33), p.4105-4116
Main Authors: Govindarajan, Dhanasekaran, Meschino, Steven, Guan, Liming, Clements, David E, ter Meulen, Jan H, Casimiro, Danilo R, Coller, Beth-Ann G, Bett, Andrew J
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - administration & dosage
Allergy and Immunology
Animals
Antibodies, Neutralizing - blood
Antibodies, Viral - blood
Cholesterol - administration & dosage
Dengue
Dengue - prevention & control
Dengue fever
Dengue Vaccines - administration & dosage
Dengue Vaccines - immunology
Disease Models, Animal
Drug Combinations
Drug Evaluation, Preclinical
Efficacy
Envelope
Female
Illnesses
Immunization
Immunization Schedule
Immunogenicity
Infections
Insects
Macaca mulatta
Male
Monkeys & apes
Neutralization
Phospholipids - administration & dosage
Proteins
Saponins - administration & dosage
Subunit vaccine
Tropical diseases
Vaccines
Vaccines, Combined - administration & dosage
Vaccines, Combined - immunology
Vaccines, Subunit - administration & dosage
Vaccines, Subunit - immunology
Vaccines, Synthetic - administration & dosage
Vaccines, Synthetic - immunology
Vector-borne diseases
Viremia - prevention & control
Viruses
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Summary:Highlights • Subunit DEN-80E protein was evaluated as monovalent and tetravalent formulations for immunogenicity and efficacy in non-human primates. • Monomeric and dimeric forms of DEN4-80E were found to be equally immunogenic/protective when formulated with ISCOMATRIX™ adjuvant. • Tetravalent DEN-80E induced high titer, well-balanced neutralizing antibodies to all 4 dengue types. • Tetravalent DEN-80E formulations offered protection against viremia following challenge even 8-12 months after last vaccine dose.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2015.06.067