Download presentation
Presentation is loading. Please wait.
1
Challenges, Consideration, and Progress
Dengue Virus Challenges, Consideration, and Progress Michaela Nickol 14 March 2019
2
Overview Dengue Virus Disease Progression
Antibody-Dependent Enhancement Vaccine Development Alternative Approaches
3
Dengue Transmitted by Aedes aegypti
Endemic in more than 100 countries throughout Africa, Asia, and America million individuals infected each year Ranges from asymptomatic to life-threatening disease Simmons et al. Viruses
4
Genome Organization Enveloped, positive-sense RNA virus
Perera and Kuhn. Current Opinions in Microbiology
5
Serotypes DENV-1 DENV-2 DENV-3 DENV-4 5 genotypes 6 genotypes
nature.com
6
Serotypes Error prone RNA-dependent polymerase
Homologous recombination Increase in migration
7
Dengue Infection Ranges from asymptomatic to life-threatening
500 million individuals infected each year 100 million symptomatic infections 20 million cases result in severe disease 20,000 deaths each year
8
Dengue Fever Acute fever Headache Myalgia Arthalgia Vomiting Weakness
Maculopapular rash Self-limiting tabletsmanual.com
9
Severe Disease – Dengue Hemorrhagic Fever
Similar to Dengue Fever Decline in platelets Vascular leakage Abdominal pain Hypotension dengueuta.weebly.com
10
Severe Disease – Dengue Shock Syndrome
Similar to Dengue Hemorrhagic Fever Severe bleeding Multi-organ involvement Hypovalaemic shock eJmanager.com
11
Disease Progression Unknown why some infections progress to DHF/DSS
Mix of factors Gender Genetic characteristics Immunological status Epidemiological factors Viral strain Secondary infection with a heterologous serotype
12
Antibody-Dependent Enhancement
Whitehead et al. Nature Reviews Microbiology
13
Antibody-Dependent Enhancement - Cuba
1977 DENV-1 epidemic 1981 DENV-2 epidemic 1997 DENV-2 epidemic 2001 DENV-3 epidemic 1975 ~2.6% of Cubans had antibodies
14
Vaccine Development No approved vaccine
Immune functions are not well-understood No sufficient animal models Accessible to resource-poor countries freeiconspng.com theconversation.com
15
Vaccine Development - ChimeriVax
Live recombinant attenuated vaccine E and prM genes cloned into yellow fever 17D vaccine Guy et al. Vaccine
16
Vaccine Development - ChimeriVax
Licensed in 20 countries Administered in 3 doses (0, 6, and 12 months) Safe for individuals between 9 and 45 years old
17
Vaccine Development - ChimeriVax
Viral interference has been observed Efficiency higher in serotypes 3 and 4 Performs differently in seropositive and seronegative individuals Increased risk of severe disease in seronegative individuals “pre-vaccination screening strategy”
18
Vaccine Development – NIH/Butantan
Live attenuated vaccine Site-directed mutagenesis to delete nucleotides in the 3’ UTR Induction of T-cell and antibody response Response raised against structural and nonstructural proteins Bos et al. Pathogens and Global Health
19
Vaccine Development - Takeda
Live attenuated recombinant chimeric vaccine Attenuated DENV-2 backbone E and prM genes of other serotypes expressed on backbone Osorio et al. Vaccine
20
Alternative Approaches - Mesocyclops
Trialed in Vietnam Reduction in A. aegypti mosquitoes Reduction in DENV incidence over several years
21
Alternative Approaches - Wolbachia
A. aegypti infected with Wolbachia bacterium Induces resistance to arboviruses Reduces lifespan by 50% Wikipedia.com
22
Questions?
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.