5 dengue vaccines in development

Currently, there are no approved vaccines or therapies to prevent dengue infection. The disease, which primarily affects children, is associated with approximately 22,000 deaths annually worldwide, according to the CDC.

Infectious Disease News has compiled information on five candidate dengue vaccines in various stages of development.

V180, Merck — phase 1

This tetravalent vaccine is designed to protect against all four dengue serotypes and contains virus components of each, which is a requirement because subsequent infections increase severity of disease. Also, infection by one serotype does not prevent infection by another. The vaccine is inactivated, containing only the truncated form of structural envelope protein, which prevents serotypes from interfering with each other. Because an inactivated virus has difficulty stimulating immunity on its own, V180 is being tested with various adjuvants to boost immunity, causing the vaccine to be tested in three doses, sometimes several months apart. It is undergoing early clinical trials in Australia.

TDENV PIV, GlaxoSmithKline and Walter Reed Army Institute of Research — phase 1 and phase 2

This tetravalent vaccine is inactivated and purified, so that the genes of each serotype are not altered like V180, making it easier to produce. In preclinical trials, TDENV PIV was given in two doses, 4 weeks apart with various adjuvants. It is undergoing phase 1 trials in the United States and Puerto Rico. In phase 2 trials, the vaccine will be given before an attenuated booster dose.

TV003, NIAID — phase 2

TV003 is a tetravalent, live-attenuated vaccine designed to induce both antibody and cellular immune responses. The vaccine is recombinant — combining nonstructural genes of serotype 4 with structural genes of serotype 2 — and can induce enough immunity to require only one dose. After being licensed for production and further evaluation by manufacturers in Brazil, India and Vietnam, TV003 is undergoing phase 2 clinical testing in Brazil and Thailand.

DENVax, Takeda — phase 2 and phase 2b

DENVax is a tetravalent, live-attenuated and recombinant vaccine candidate, combining nonstructural genes of serotype 2 with structural genes of serotypes 1, 3 and 4. It is given in two doses, 3 months apart. It is undergoing phase 2 trials in Thailand, Singapore, Colombia and Puerto Rico.

CYD-TDV, Sanofi Pasteur — phase 3

Like DENVax and TV003, the CYD-TDV vaccine is tetravalent, live-attenuated and recombinant. However, it incorporates nonstructural genes of yellow fever virus with structural genes of all four serotypes. It is administered in three doses at 6-month intervals.

In phase 3 trials, CYD-TDV showed an overall efficacy of 56%, but only an efficacy of 35.5% in patients without previous dengue exposure, suggesting that it functions primarily as an immune enhancement for older patients with partial immunity.

The Sanofi vaccine is the furthest along in development; however, it may only work for older patients and limit its use. However, because of its overall efficacy, CYD-TDV can still significantly reduce the massive burden of dengue, for which 40% of the world lives in at-risk areas. 

References:

CDC. Current status of dengue vaccine development. http://www.who.int/immunization/sage/meetings/2013/april/2_Roehrig_Dengue_SAGE_April2013.pdf. Accessed August 26, 2015.

CDC. http://www.cdc.gov/dengue/epidemiology/. Accessed September 3, 2015.

CDC. http://www.cdc.gov/dengue/faqfacts/index.html. Accessed August 26, 2015.

Coller B-AG, et al. Curr Opin Immunol. 2011;doi:10.1016/j.coi.2011.03.005.

Merck. Merck Dengue Vaccine Program. http://www.denguevaccines.org/sites/default/files/files/Day%201_2_4_Merck_SGupta.pdf. Accessed August 26, 2015.

NIH. Dengue vaccines: How close are we? https://www.informedhorizons.com/hepdart2013/HVBD/pdf/Presentations/Whitehead_MAC%202013%20HEPDART-Whitehead.pdf. Accessed September 3, 2015.

NIH. http://www.nih.gov/news/health/jan2013/niaid-23.htm. Accessed September 3, 2015.

Schwartz LM, et al. Vaccine. 2015;doi:10.1016/j.vaccine.2015.05.010.

Wilder-Smith A. Lancet. 2014;doi:10.1016/S0140-6736(14)61142-9.

Currently, there are no approved vaccines or therapies to prevent dengue infection. The disease, which primarily affects children, is associated with approximately 22,000 deaths annually worldwide, according to the CDC.

Infectious Disease News has compiled information on five candidate dengue vaccines in various stages of development.

V180, Merck — phase 1

This tetravalent vaccine is designed to protect against all four dengue serotypes and contains virus components of each, which is a requirement because subsequent infections increase severity of disease. Also, infection by one serotype does not prevent infection by another. The vaccine is inactivated, containing only the truncated form of structural envelope protein, which prevents serotypes from interfering with each other. Because an inactivated virus has difficulty stimulating immunity on its own, V180 is being tested with various adjuvants to boost immunity, causing the vaccine to be tested in three doses, sometimes several months apart. It is undergoing early clinical trials in Australia.

TDENV PIV, GlaxoSmithKline and Walter Reed Army Institute of Research — phase 1 and phase 2

This tetravalent vaccine is inactivated and purified, so that the genes of each serotype are not altered like V180, making it easier to produce. In preclinical trials, TDENV PIV was given in two doses, 4 weeks apart with various adjuvants. It is undergoing phase 1 trials in the United States and Puerto Rico. In phase 2 trials, the vaccine will be given before an attenuated booster dose.

TV003, NIAID — phase 2

TV003 is a tetravalent, live-attenuated vaccine designed to induce both antibody and cellular immune responses. The vaccine is recombinant — combining nonstructural genes of serotype 4 with structural genes of serotype 2 — and can induce enough immunity to require only one dose. After being licensed for production and further evaluation by manufacturers in Brazil, India and Vietnam, TV003 is undergoing phase 2 clinical testing in Brazil and Thailand.

DENVax, Takeda — phase 2 and phase 2b

DENVax is a tetravalent, live-attenuated and recombinant vaccine candidate, combining nonstructural genes of serotype 2 with structural genes of serotypes 1, 3 and 4. It is given in two doses, 3 months apart. It is undergoing phase 2 trials in Thailand, Singapore, Colombia and Puerto Rico.

CYD-TDV, Sanofi Pasteur — phase 3

Like DENVax and TV003, the CYD-TDV vaccine is tetravalent, live-attenuated and recombinant. However, it incorporates nonstructural genes of yellow fever virus with structural genes of all four serotypes. It is administered in three doses at 6-month intervals.

In phase 3 trials, CYD-TDV showed an overall efficacy of 56%, but only an efficacy of 35.5% in patients without previous dengue exposure, suggesting that it functions primarily as an immune enhancement for older patients with partial immunity.

The Sanofi vaccine is the furthest along in development; however, it may only work for older patients and limit its use. However, because of its overall efficacy, CYD-TDV can still significantly reduce the massive burden of dengue, for which 40% of the world lives in at-risk areas. 

References:

CDC. Current status of dengue vaccine development. http://www.who.int/immunization/sage/meetings/2013/april/2_Roehrig_Dengue_SAGE_April2013.pdf. Accessed August 26, 2015.

CDC. http://www.cdc.gov/dengue/epidemiology/. Accessed September 3, 2015.

CDC. http://www.cdc.gov/dengue/faqfacts/index.html. Accessed August 26, 2015.

Coller B-AG, et al. Curr Opin Immunol. 2011;doi:10.1016/j.coi.2011.03.005.

Merck. Merck Dengue Vaccine Program. http://www.denguevaccines.org/sites/default/files/files/Day%201_2_4_Merck_SGupta.pdf. Accessed August 26, 2015.

NIH. Dengue vaccines: How close are we? https://www.informedhorizons.com/hepdart2013/HVBD/pdf/Presentations/Whitehead_MAC%202013%20HEPDART-Whitehead.pdf. Accessed September 3, 2015.

NIH. http://www.nih.gov/news/health/jan2013/niaid-23.htm. Accessed September 3, 2015.

Schwartz LM, et al. Vaccine. 2015;doi:10.1016/j.vaccine.2015.05.010.

Wilder-Smith A. Lancet. 2014;doi:10.1016/S0140-6736(14)61142-9.