- Email: [email protected]
A Dengue Vaccine
Leading Edge
Bench to Bedside A Dengue Vaccine Anna P. Durbin
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA *Correspondence: [email protected] http://dx.doi.org/10.1016/j.cell.2016.06.036 NAME
CYDTM
Structural proteins
Dengvaxia
Non-structural proteins From yellow fever
From Dengue
5´
C prM
E
NS1 NS2A NS2B NS3 NS4A NS4B
NS5
3´ CYD-1
5´
C prM" E
NS1 NS2A NS2B NS3 NS4A NS4B
NS5
3´ CYD-2
5´
C prM" E
NS1 NS2A NS2B NS3 NS4A NS4B
NS5
3´ CYD-3
5´
C prM" E
NS1 NS2A NS2B NS3 NS4A NS4B
NS5
3´ CYD-4
APPROVED FOR
Persons 9–45 years of age living in highly dengue endemic regions of Mexico, the Philippines, Brazil, and El Salvador. WHO SAGE recommends vaccine use in places with high dengue endemicity (seroprevalence ≥ 70% in the age group targeted) TYPE
DENGUE VIRUS
A recombinant chimeric live attenuated tetravalent vaccine MOLECULAR TARGETS
The envelope protein of all four dengue viruses CELLULAR TARGETS
The vaccine induces antibodies to each of the four dengue virus serotypes. EFFECTS ON TARGETS
Envelope (E) protein
Neutralizing antibodies bind to epitopes on the E protein to inactivate the virus and to prevent viral entry. Incomplete or partially neutralizing antibodies can assist viral entry into monocytes and macrophages through the Fcγ receptor (antibody-mediated enhancement of infection).
Dengvaxia is the first licensed vaccine for the prevention of dengue. It is a live vaccine developed using recombinant DNA technology. The vaccine is given as three doses over the course of a year and has the potential to prevent hundreds of thousands of hospitalizations each year.
DEVELOPED BY
Sanofi Pasteur
Dengue is endemic in more than 100 countries
Spectrum of illness
200 million total cases of Dengue fever
1 in 2
cases are symptomatic
35,000
enrolled in Dengvaxia efficacy trials 1945 Albert Sabin describes use of mouse-adapted dengue virus as a vaccine 2001 Biologically derived live attenuated dengue vaccine approach abandoned due to excessive reactogenicity
1945
2000
2006 First clinical trial results of the recombinant chimeric live attenuated tetravalent vaccine CYD (now Dengvaxia)
2005
ASYMPTOMATIC SYMPTOMATIC
Global distribution
2012 Phase 2b trial in Thailand demonstrates only 30.2% efficacy 2014 Phase 3 trials in Asia and Latin America demonstrate 56%–61% efficacy against dengue and 67%–80% efficacy against hospitalization
250k-500k
Dengue hemorrhagic fever Dengue shock syndrome Classic dengue fever Dengue fever unreported
~99.5 MILLION
Undifferentiated febrile illness
Mildly symptomatic dengue Asymtomatic dengue 100 MILLION
2015 Increased risk of hospitalization 2 years after vaccination reported in children less than 9 years old at vaccination 2015 Licensure in Mexico, the Philippines, and Brazil
2015
2010
References for further reading are available with this article online: www.cell.com/cell/fulltext/S0092-8674(16)30807-8
Cell 166, June 30, 2016 © 2016 Published by Elsevier Inc. 1
Bench to Bedside A Dengue Vaccine Anna P. Durbin
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA *Correspondence: [email protected] http://dx.doi.org/10.1016/j.cell.2016.06.036 NAME
CYDTM
Structural proteins
Dengvaxia
Non-structural proteins From yellow fever
From Dengue
5´
C prM
E
NS1 NS2A NS2B NS3 NS4A NS4B
NS5
3´ CYD-1
5´
C prM" E
NS1 NS2A NS2B NS3 NS4A NS4B
NS5
3´ CYD-2
5´
C prM" E
NS1 NS2A NS2B NS3 NS4A NS4B
NS5
3´ CYD-3
5´
C prM" E
NS1 NS2A NS2B NS3 NS4A NS4B
NS5
3´ CYD-4
APPROVED FOR
Persons 9–45 years of age living in highly dengue endemic regions of Mexico, the Philippines, Brazil, and El Salvador. WHO SAGE recommends vaccine use in places with high dengue endemicity (seroprevalence ≥ 70% in the age group targeted) TYPE
DENGUE VIRUS
A recombinant chimeric live attenuated tetravalent vaccine MOLECULAR TARGETS
The envelope protein of all four dengue viruses CELLULAR TARGETS
The vaccine induces antibodies to each of the four dengue virus serotypes. EFFECTS ON TARGETS
Envelope (E) protein
Neutralizing antibodies bind to epitopes on the E protein to inactivate the virus and to prevent viral entry. Incomplete or partially neutralizing antibodies can assist viral entry into monocytes and macrophages through the Fcγ receptor (antibody-mediated enhancement of infection).
Dengvaxia is the first licensed vaccine for the prevention of dengue. It is a live vaccine developed using recombinant DNA technology. The vaccine is given as three doses over the course of a year and has the potential to prevent hundreds of thousands of hospitalizations each year.
DEVELOPED BY
Sanofi Pasteur
Dengue is endemic in more than 100 countries
Spectrum of illness
200 million total cases of Dengue fever
1 in 2
cases are symptomatic
35,000
enrolled in Dengvaxia efficacy trials 1945 Albert Sabin describes use of mouse-adapted dengue virus as a vaccine 2001 Biologically derived live attenuated dengue vaccine approach abandoned due to excessive reactogenicity
1945
2000
2006 First clinical trial results of the recombinant chimeric live attenuated tetravalent vaccine CYD (now Dengvaxia)
2005
ASYMPTOMATIC SYMPTOMATIC
Global distribution
2012 Phase 2b trial in Thailand demonstrates only 30.2% efficacy 2014 Phase 3 trials in Asia and Latin America demonstrate 56%–61% efficacy against dengue and 67%–80% efficacy against hospitalization
250k-500k
Dengue hemorrhagic fever Dengue shock syndrome Classic dengue fever Dengue fever unreported
~99.5 MILLION
Undifferentiated febrile illness
Mildly symptomatic dengue Asymtomatic dengue 100 MILLION
2015 Increased risk of hospitalization 2 years after vaccination reported in children less than 9 years old at vaccination 2015 Licensure in Mexico, the Philippines, and Brazil
2015
2010
References for further reading are available with this article online: www.cell.com/cell/fulltext/S0092-8674(16)30807-8
Cell 166, June 30, 2016 © 2016 Published by Elsevier Inc. 1