Dengue Vaccines

Authored by
Staff
Last reviewed
November 16, 2021

Dengue Vaccines

The World Health Organization recommends that the Dengvaxia vaccine be given to persons with confirmed prior dengue virus infection. And the U.S. FDA authorized the Dengvaxia vaccine for limited use on May 1, 2019, for people with laboratory-confirmed previous dengue infection and living in endemic areas.

On June 24, 2021, the U.S. CDC's Advisory Committee on Immunization Practices (ACIP) presented updated dengue vaccine considerations. And as of September 1, 2021, the U.S. CDC confirmed 32 dengue cases and 367 in the U.S. Territories (Puerto Rico).

In 2021, over 1.3 million dengue cases have been reported, the majority from Brazil (845,720), India (60,112), Vietnam (53,489), Peru (37,728), and The Philippines (32,555). Since Week #39 reporting, India (46,068) and Brazil (31,839) have confirmed the most cases to the ECDC.

Dengue Vaccines

Dengvaxia (CYD-TDV, Dengue Tetravalent Vaccine, Live) is a live attenuated tetravalent chimeric vaccine made using recombinant DNA technology by replacing the PrM (pre-membrane) and E (envelope) structural genes of yellow fever attenuated 17D strain vaccine and is indicated for the prevention of dengue disease caused by dengue virus serotypes 1, 2, 3 and 4. The CDC's ACIP workgroup used the Evidence to Recommendations Framework to explore whether three doses of Dengvaxia should be administered routinely to persons 9–16 years of age with laboratory-confirmed previous dengue infection and living in endemic areas (Puerto Rico). Patients must receive a lab test showing a past infection with dengue before receiving the vaccine.

TAK-003 is an investigational live-attenuated tetravalent dengue vaccine, preventing dengue fever caused by any of the four serotypes of the dengue virus, each of which can cause dengue fever or Severe Dengue. Takeda announced that the European Medicines Agency had accepted the Company's filing packages for TAK-003. Takeda also intends to submit regulatory filings in Argentina, Brazil, Colombia, Indonesia, Malaysia, Mexico, Singapore, Sri Lanka, and Thailand during 2021.

The DV1-DV4 vaccine candidate is transitioning into human clinical study. This new vaccine construct, which comprises Nature's gene-chip peptides bound to a quantum cluster gold nanoparticle delivery system, was shown to have an excellent safety profile in a repeat dose Good Laboratory Practice grade toxicology study using a standard industry model.

TetraVax-DV-TV003 is a live attenuated recombinant tetravalent investigational dengue vaccine. Dr. Stephen Whitehead's laboratory developed the vaccine at NIH's National Institute of Allergy and Infectious Diseases.

Àvida Biotech's novel oral vaccine candidate for dengue does not require cold transport or storage and has completed proof of concept in a mouse model. In addition, the University of Buffalo's Center for Integrated Global Biomedical Sciences will provide preclinical drug development expertise.

Merck V180 (V181) is a Phase I Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Tetravalent Recombinant Subunit Dengue Vaccine (V180) in Healthy Adults. The US FDA has granted V181, the Company's investigational dengue vaccine in Phase 1 development, Fast Track designation.

K.M. Biologics KD-382 vaccine is a live attenuated tetravalent dengue vaccine candidate in phase 1 clinical trial that is expected to be effective against all four serotypes with a single dose. In addition, this live attenuated virus vaccine is expected to induce neutralizing antibodies and cellular immunity, similar to natural infection.

Emergex PepGNP-Dengue vaccine candidate uses 100% synthetic vaccines to 'prime' naive CD8+ T-Cells to generate virus-specific CTL (CD8+ Cytotoxic T Lymphocyte cells) to kill infected cells before productive viral infection (host cells releasing intact virions), thus preventing viral replication and disease in the vaccinated person.

Dengue Vaccine News

November 14, 2021 - Haryana confirmed three dengue deaths reported the Times of India. At 8,819, the official dengue count in Haryana is the highest in five years.

October 28, 2021 - The Times of India confirmed a dengue outbreak has impacted about 300 people and caused several deaths in rural areas of Roorkee and Bhagwanpur.

October 13, 2021 - The journal PLOS published: Economic impact of dengue in Singapore from 2010 to 2020 and the cost-effectiveness of Wolbachia interventions. Wolbachia releases in Singapore are expected to be highly cost-effective, and its rollout must be prioritized to reduce the onward spread of the dengue virus in humans.

October 9, 2021 - BMC Infectious Disease published: Clinical predictors of severe dengue: a systematic review and meta-analysis. Conclusions - Our meta-analysis identified children, secondary infection, diabetes, and renal disease(s) as important predictors of severe dengue. Our finding also supports the predictive ability of the WHO warning signs to identify severe dengue. These findings are useful for clinicians to identify severe dengue for management and timely interventions.

October 6, 2021 - The Janssen Pharmaceutical Companies of Johnson & Johnson announced in collaboration with the KU Leuven Rega Institute and the KU Leuven Centre for Drug Design and Discovery, the publication of new preclinical data in the journal Nature showing that an early-stage compound with a novel mechanism of action could potentially treat all serotypes of dengue fever and provide a period of protection against acquiring the dengue virus. Janssen is now moving its dengue program into clinical development. Data from the early-stage study suggest that an antiviral compound prevents the interaction between two viral proteins (NS3 and NS4B) that play an important role in the replication process of a virus, thereby stopping the ability of the virus to reproduce. This represents an entirely novel mechanism of antiviral action.

October 5, 2021 -  The Tamil Nadu Health Department has reported 2,930 dengue cases in 2021 and of this, 337 are active. Around 20 cases are reported per day in the state. There have also been two deaths.

October 4, 2021 - Clinical Infectious Diseases published: Three years efficacy and safety of Takeda's dengue vaccine candidate (TAK-003), which concluded by stating 'TAK-003 was efficacious against symptomatic dengue over three years. Efficacy declined over time but remained robust against hospitalized dengue.'

September 30, 2021 - The U.S. CDC issued Watch - Level 1, Practice Usual Precautions Alerts regarding dengue outbreaks in Africa, Asia, the Americas, the Middle East, and the Pacific Islands.

September 24, 2021 - The BMC Network published Krisztian Magori, who provides an update on the most recent developments in the use of Wolbachia in reducing dengue infections in Indonesia, with very encouraging results.

September 23, 2021 - Principal Secretary Health Mr. Alok Shekhar stated that an upsurge in dengue cases has been reported in Punjab, India, with 1,724 confirmed cases from across Amritsar, Hoshiarpur, Sri Muktsar Sahib, SAS Nagar, Bathinda, and Pathankot. The Government of Punjab has increased the number of testing labs to 39. He added that testing and treatment of dengue is free of cost in all Government hospitals.

September 23, 2021 - A non-peer-reviewed study: Immune profile and responses of a novel Dengue DNA vaccine encoding EDIII-NS1 consensus design based on Indo-African sequences. Dengue DNA platform focusing on Indo-African sequences offers an approach for assessing cross-reactive immunity in animal models and lays the foundation for human vaccine roll out either as a stand-alone or mix and match strategy.

September 13, 2021 - Miss Universe Philippines 2021 contracts dengue and withdraws from the competition.

September 9, 2021 - The WHO published Update #628 on the Dengue situation in the Western Pacific Region. As of epidemiological week 33, a total of 10 deaths due to dengue have been reported in 2021, compared to 113 deaths during the same period in 2020.

September 8, 2021 - India's local media reported preliminary figures to show UP's Firozabad is one district confronting dengue virus outbreaks. As many as 105 new cases of dengue and viral fever were reported on September 5, 201. The death toll is reported to have mounted to 55, with most casualties being children.

August 24, 2021 - Atea Pharmaceuticals announced data demonstrating the in vitro and in vivo activity of AT-752 against dengue virus infection in the journal, Antimicrobial Agents and Chemotherapy. The published data demonstrate that AT-752 has potent in vitro activity against multiple dengue virus serotypes and other flaviviruses tested, reduces viremia, and improves survival in an animal model of dengue disease.

August 20, 2021 - The International Journal of Infectious Diseases published a study: Serotype and genotype diversity of dengue viruses circulating in India: A multicentre retrospective study involving virus research diagnostic laboratory network during 2018. The results revealed DENV-2 as the most prevalent serotype in many states. In addition, Thrombocytopenia, petechiae, and malaise were associated with DENV-2 infection. Phylogenetic analyses of DENV E gene sequences revealed the circulation of genotypes I and V of DENV-1, two lineages of DENV-2 genotype IV, DENV-3 genotype III, and DENV-4 genotype-I.

July 12, 2021 - The Lancet published an article: Knowledge gaps in the epidemiology of severe dengue impede vaccine evaluation. 'To improve our understanding of the diverse factors that shape the clinical spectrum of disease resulting from dengue virus infection, prospective, community-based and clinic-based immunological, virological, genetic, and clinical studies across a range of ages and geographical regions are needed.'

July 5, 2021 - New Delhi local media reported the South Delhi Municipal Corporation India revealed the number of dengue cases (36) from January 1 to July 3, 2021, is the highest this year since 2018.

June 30, 2021 - Emergex Vaccines Holding Limited announced that it had achieved regulatory approval for a Phase I clinical trial of its PepGNP-Dengue vaccine. The study has received approval from Swiss regulatory agencies, and the first participants are expected to be enrolled soon.

June 25, 2021 - The ACIP committee met to review the Acceptability and Implementation of dengue vaccines in Puerto Rico.

June 24, 2021 - UNC School of Medicine scientists led by Aravinda de Silva, Ph.D., identified the small subpopulation of antibodies in vaccinated children that correlate with protection against dengue fever. This research, published on May 18, 2021, should help shape better vaccines for one of the most widespread infectious diseases in the world.

June 11, 2021 - In Réunion, French authorities have reported 20,800 confirmed dengue cases for 2021, with the whole territory affected. This represents an increase of 4,602 cases since the last report with data as of May 25, 2021. Among the hospitalized dengue cases, 20% had severe dengue, a slightly higher proportion than in 2019 (17%) and 2020 (16%). Twelve deaths are considered directly related to dengue.

June 10, 2021 - The NEJM reported a fatal case of dengue in Florida. 'Ensuring appropriate patient care management, including close clinical monitoring and judicious use of intravenous fluids, can reduce dengue case-fatality rates. Therefore, clinicians should suspect dengue and order molecular testing for patients with acute febrile illness and relevant epidemiologic exposure because knowledge of this infection may alter clinical care.'

June 10, 2021 - The NEJM published 'Efficacy of Wolbachia-infected Mosquito Deployments for the Control of Dengue.' This study concluded 'Introgression of wMel into A. aegypti populations effectively reduced the incidence of symptomatic dengue and resulted in fewer hospitalizations for dengue among the participants.'

May 22, 2021 - Takeda Pharmaceutical announced that TAK-003 demonstrated continued protection against dengue illness and hospitalization, regardless of an individual's previous dengue exposure.

May 6, 2021 - The U.S. CDC issued a Level 1 Travel Alert regarding dengue outbreaks in South and Central America, Mexico, and the Caribbean. 

May 5, 2021 - The U.S. CDC's ACIP committee Gabriela Paz Bailey, MD, Ph.D., MSc presented 'Dengue Vaccine Evidence to recommendations framework.'

April 12, 2021 - Review Article: Dengue Virus and Vaccines: How Can DNA Immunization Contribute to This Challenge?

April 2, 2021 - French media reported, 'With 758 cases of dengue confirmed from March 15 to 21, the epidemic is accelerating on Reunion Island. Twenty municipalities are concerned with groupings of cases mainly located in the West at Port, Saint-Paul, and La Possession, and in the South at Saint-Joseph. To date, only serotype 1 has been detected among the confirmed cases.

March 31, 2021 - In 2021, and as of week #12, the Pan American Health Organization had reported 175,372 suspected and confirmed dengue cases and 32  associated deaths in the Americas region. The five countries reporting the most cases are Brazil (130,013), Nicaragua (9,207), Peru (7 953), Colombia (7,247), Paraguay (6,938). In addition, all four dengue virus serotypes (DENV 1, DENV 2, DENV 3, and DENV 4) are currently circulating in the region of the Americas, which increases the risk of severe cases. The figures for each country of the Americas region can be found on the PAHO Health Information Platform.

March 25, 2021 - Takada announced the European Medicines Agency is conducting the First-Ever Parallel Assessment of a Medicinal Product, Takeda's Dengue Vaccine Candidate (TAK-003), for use in the E.U.; Countries Outside of the E.U. through the EU-M4all (Previously Article 58) Procedure. Furthermore, Takeda Intends to Submit Regulatory Filings in Argentina, Brazil, Colombia, Indonesia, Malaysia, Mexico, Singapore, Sri Lanka, and Thailand during 2021.

March 25, 2021 - Japan-based KM Biologics Co., Ltd. announced Phase I clinical study of a live attenuated tetravalent vaccine, KD-382, to prevent dengue. The results show that the KD-382 vaccine is safe and well-tolerated by healthy adults. Moreover, KD-382 showed 100% seroconversion early and elicited long-lasting and neutralizing antibody response for all 4 serotypes in most subjects over a 1-year follow-up, despite the single-dose administration. Based on the supporting results indicating the KD-382 vaccine as very promising, the Company is preparing for Phase II clinical studies.

March 3, 2021 - The U.S. CDC reported 5 dengue cases had been confirmed in the USA during 2021. And U.S. Territories (Puerto Rico) have confirmed 85 dengue cases.

March 2, 2021 - The U.S.CDC issued a Level 1 Travel Alert for many parts of Central and South America, Mexico, and the Caribbean regarding Dengue virus risks. 

February 25, 2021 - The Lancet published a systematic review and meta-analysis of Risk predictors of progression to severe disease during the febrile phase of dengue. This analysis supports monitoring of the warning signs described in the 2009 WHO guidelines on dengue. Also, testing for infecting serotype and monitoring platelet count and serum albumin, AST, and ALT concentrations during the febrile phase of illness could improve the early prediction of severe dengue.

December 4, 2020 - Researchers from the United Kingdom announced they used plants to produce virus-like particles (VLPs) of the dengue virus in a potential first step towards novel vaccines against the growing threat.

November 30, 2020 - The South American country of the Republic of Peru has resumed most transportation options, including airport operations. In addition, other improved conditions such as the resumption of most business operations and a gradual re-opening of borders have been reported within Peru. 

November 16, 2020 - Study published by The Lancet: Accuracy and efficacy of pre-dengue vaccination screening for previous dengue infection with five commercially available immunoassays: a retrospective analysis of phase 3 efficacy trials. Each immunoassay's specificity and sensitivity were determined as percentage negative and positive, compared with the reference algorithm, which used dengue plaque reduction neutralization test with 50% and 90% cutoffs and non-structural protein 1 IgG ELISA results to assign baseline serostatus. These findings suggest that these immunoassays could be used for pre-vaccination screening for CYD-TDV as tools to assist risk stratification until more sensitive and convenient tests become available.

November 16, 2020 - A new study published by The Lancet found 'Previous trials have provided some evidence that antibody responses elicited after just one dose or two doses of CYD-TDV might be similar to those elicited after three doses. They compared antibody responses following one-dose, two-dose, and three-dose vaccination regimens in individuals who were dengue seropositive at baseline up to 1 year after the last injection. They reported a 2-dose CYD-TDV regimen might be an alternative to the licensed 3-dose regimen in individuals who are dengue seropositive at baseline and aged 9 years and older. Vaccination with a reduced number of doses could improve vaccine compliance and coverage, especially in low-resource settings.

November 16, 2020 - Study: A prospective population-based study will determine dengue virus serostatus by indirect IgG ELISA compared with focus reduction neutralization test in children in Cebu, Philippines. Compared with FRNT, ELISA had high sensitivity and specificity (>90%), but the false-negative and false-positive rates make the test suboptimal for prevaccination screening. Individuals falsely identified as seropositive by dengue IgG ELISA and then vaccinated might be at risk of developing the severe disease during subsequent exposure to wild-type dengue virus. Those with a monotypic profile would benefit the most from vaccination. Still, the IgG ELISA's sensitivity was much lower in this group than in those with a multitypic profile.

November 9, 2020 - Clinical trial: Zika and Dengue Interactions in the Context of a Large Dengue Vaccine Clinical Trial in Latin America. Dengue vaccine does not enhance symptomatic Zika illness in dengue-seropositive individuals; rather, it reduces the risk of virologically confirmed Zika. In addition, Zika infection boosts preexisting vaccine-induced or naturally occurring dengue-neutralizing antibodies.

November 4, 2020 - The University of Buffalo's Center for Integrated Global Biomedical Sciences (CIGBS) will partner with Àvida Biotech, a Spain-based developer of antiviral products, to advance affordable, new antivirals and vaccines for neglected infectious diseases such as the dengue. The CIGBS scientists will support Àvida Biotech's investigation of a novel oral vaccine for dengue that does not require cold transport or storage.

October 27, 2020 - According to new clinical trials conducted in Iquitos, Peru, Spatial repellents can reduce the risk of infected people with Aedes mosquito-borne viruses. According to the University of Notre Dame, the Peru trial results are encouraging — study participants whose houses contained the spatial repellent were 34 percent less likely to become infected with Aedes mosquito-borne viruses than other study participants who received the placebo product without the repellent. The Iquitos trial was part of a multi-year effort led by scientists at the University of Notre Dame to determine the protective efficacy of spatial repellents to prevent human infection with pathogens that cause diseases such as malaria, Zika, and dengue, spread through mosquito bites.

October 25, 2020 - Study: Plant‐made dengue virus‐like particles produced by co‐expression of structural and non‐structural proteins induce a humoral immune response in mice. These results are consistent with the idea that VLPs could be optimal for creating candidate vaccines against enveloped viruses.

October 14, 2020 - The U.S. CDC issued a Level 1 Travel Alert for the Americas. Dengue is an ongoing risk in many parts of Central and South America, Mexico, and the Caribbean (map). Travelers to areas of risk should protect themselves by preventing mosquito bites.

September 22, 2020 - The Florida Department of Health in Miami-Dade County (DOH-Miami-Dade) is under a mosquito-borne illness alert. A case of dengue fever of local transmission has been confirmed in a Miami-Dade resident. There has been a total of two locally acquired dengue cases in 2020.

September 21, 2020 - The authors of a non-peer-reviewed study hypothesized that a safe and effective dengue vaccine could offer some immunity against SARS-CoV-2.

August 27, 2020 - The World Mosquito Program (WMP) of Monash University and its Indonesian partners, the Tahija Foundation and Universitas Gadjah Mada have announced the first results of a cluster randomized controlled trial of its Wolbachia method, showing a 77% reduction in the incidence of virologically-confirmed dengue in Wolbachia-treated areas of Yogyakarta, Indonesia, compared to untreated areas. 

August 7, 2020 - The regional health authorities of Occitanie reported an autochthonous dengue transmission in Cessenon-surOrb, in Hérault prefecture. This case was infected in mid-July. The competent authorities are undertaking response measures, and outbreak investigations have identified the primary case in a returning traveler from a dengue risk zone. This is the first autochthonous transmission reported in continental France in 2020. Background: Autochthonous dengue cases have been reported in continental Europe in recent years. In 2019, ten cases were reported in France (9) and Spain (1). In addition, one additional sexual transmission of dengue was reported in Madrid, Spain, in 2019.

July 23, 2020 - The Florida Department of Health (DOH) recently issued a mosquito-borne illness alert following the detection of locally-acquired dengue fever cases in Monroe County, the jurisdiction that includes the Florida Keys in South Florida.

July 13, 2020 - Long-term safety and immunogenicity of a tetravalent dengue vaccine candidate in children and adults: a randomized, placebo-controlled, phase 2 study.

June 23, 2020 - A Phase 1, Open-Label- Assessment of a Dengue Virus-1 Live Virus Human Challenge - (DENV-1-LVHC) Strain.

June 9, 2020 - The World Mosquito Program of Monash University and its Indonesian partners the Tahija Foundation and Universitas Gadjah Mada have announced the first results of a cluster randomized controlled trial of its Wolbachia method, showing a 77% reduction in the incidence of virologically-confirmed dengue in Wolbachia-treated areas of Yogyakarta, Indonesia, compared to untreated areas. 

May 21, 2020 - The ongoing Dengue risk in the Americas continues into the summer of 2020, says the US Centers for Disease Control and Prevention (CDC). The CDC announced many parts of Central and South America, Mexico, and the Caribbean have continued to report dengue fever cases.

March 17, 2020 - Results published in the first paper from an 18-month analysis of ongoing pivotal Phase 3 trial were generally consistent with overall efficacy and safety data reported in the previously published 12-month analysis.

February 26, 2020 - The Chile Ministry of Health informed the WHO of confirmed autochthonous dengue fever cases reported on Easter Island. These 3 cases are middle-aged females with no recent travel history.

November 6, 2019 - New England Journal of Medicine publishes primary endpoint analysis from an ongoing Phase 3 study of Takeda's dengue vaccine candidate. TAK-003 was efficacious against symptomatic dengue in countries in which the disease is endemic. 

August 23, 2019 - Study: Pre-vaccination screening strategies for using the CYD-TDV dengue vaccine: A meeting report. The meeting discussions highlighted many challenges in introducing Dengvaxia, screening test characteristics, costs of such tests combined with a 3-dose schedule, logistics, high coverage rates, vaccine confidence, communication; more challenges than any other vaccine introduction program.

July 15, 2019 - Assessment of a Dengue-1-Virus-Live Virus Human Challenge - (DENV-1-LVHC) Virus Strain.

January 26, 2019 - This mosquito-borne disease, known as 'break-bone fever' due to its sometimes painful symptoms, infects many U.S. travelers.

November 14, 2018 - Preliminary data regarding a live-attenuated tetravalent dengue vaccine candidate developed by Takeda show that the vaccine may protect against all four serotypes of the infection, according to research presented at the annual meeting of the American Society of Tropical Medicine and Hygiene.

Dengue Virus Antigen Detection

NS1 tests detect the non-structural protein NS1 of the dengue virus. This protein is secreted into the blood during dengue infection. NS1 tests have been developed for use in serum. Most of these tests use synthetically labeled antibodies to detect dengue NS1 protein, says the U.S. CDC.

Dengue Overview

Dengue is a mosquito-borne viral infection that is common in warm, tropical climates. Infection is caused by any one of four closely related dengue viruses (called serotypes). These can lead to a wide spectrum of symptoms, including extremely mild to those that may require medical intervention and hospitalization, says the Florida Department of Health.

Dengue virus (DENV) is responsible for an estimated 100 million symptomatic cases of infection and 10,000 deaths annually. The incidence of dengue has been doubling every decade since 1990.

Dengue is common in the U.S. territories of Puerto Rico, the U.S. Virgin Islands, and American Samoa, says the U.S. CDC.

Note: The content on this webpage is aggregated from the WHO, the U.S. CDC, research studies, and various media sources. This content is reviewed for efficacy by healthcare providers, such as Dr. Bob Carlson.