Key concepts, strategies, and challenges in dengue vaccine development: an opportunity for sub-unit candidates?
Despite 70 years of research that has intensified in the past decade, a safe and efficacious dengue vaccine has yet to be available. In addition to the expected challenges such as identifying immune correlates of protection, the dengue vaccine field has faced additional hurdles including the necessity to design a tetravalent formulation and the risk of antibody-mediated disease enhancement. Nevertheless, tetravalent live attenuated vaccine candidates have reached efficacy trials and demonstrated some benefit, despite imbalanced immunogenicity and incomplete protection against the four serotypes. Meanwhile, the development of sub-unit dengue vaccines has gained momentum. As the target of most of the neutralizing antibodies so far reported, the virus envelope E protein has been the focus of much effort and represents the leading dengue sub-unit vaccine candidate. However, its notorious poor immunogenicity has prompted the development of innovative approaches to make E-derived constructs part of the second generation dengue vaccines portfolio.
a Department of Microbiology and Immunology, Yong Loo Lin School of Medicine , National University of Singapore , Singapore.
Jian Hang
JH
Lam
b Immunology programme, Life Sciences Institute , National University of Singapore , Singapore.
Li Ching
LC
Ong
a Department of Microbiology and Immunology, Yong Loo Lin School of Medicine , National University of Singapore , Singapore.|b Immunology programme, Life Sciences Institute , National University of Singapore , Singapore.
Sylvie
S
Alonso
D053059:Dengue Vaccines / Q000276:immunology* / Q000302:isolation & purification*; D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D006801:Humans; D014613:Vaccines, Attenuated / Q000276:immunology / Q000302:isolation & purification; D022223:Vaccines, Subunit / Q000276:immunology / Q000302:isolation & purification; D014759:Viral Envelope Proteins / Q000276:immunology
D053059:Dengue Vaccines; D014613:Vaccines, Attenuated; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins
EDIII; antibody-dependent enhancement (ADE); dengue; tetravalent; vaccine