Challenges To Vaccine Development
Infection by one of the four dengue virus serotypes has been shown to confer lasting protection against homotypic re-infection, but only transient protection against a secondary heterotypic infection. Moreover, secondary heterotypic infection is associated with an increased risk of severe disease. This and other observations suggest an immunopathological component in dengue pathogenesis, which is referred to as immune enhancement of disease. Due to these dengue-specific complexities, vaccine development focuses on the generation of a tetravalent vaccine aimed at providing long-term protection against all virus serotypes. Additional challenges are posed by the lack of an adequate animal disease model and the resulting uncertainty around correlates of protection. In spite of these challenges, vaccine development has made remarkable progress in recent years, and the current dengue vaccine pipeline is advanced, diverse and overall promising.
Virology Of Dengue Virus
Dengue virus is an arthropod-borne pathogen that infects humans by a bite of an infected mosquito . Two types of mosquitos can be infected by the dengue virus: Aedes aegypti or Aedes albopictus . Dendritic cells and macrophages are primarily targeted by the virus in the first days of dengue virus infections . There is no human-to-human transmission, and the virus is only transmitted through mosquitos when taking blood from a viremic individual. Viremia and systemic infection can be accomplished due to lymphotropic characteristics of the virus in which the DENV infects skin-draining lymph nodes and the cells that traffic into them, such as DCs and monocytes .
What Geographic Areas Are At High Risk For Contracting Dengue Fever
According to the Centers for Disease Control , the dengue virus is prevalent throughout the tropics and subtropics . Outbreaks have occurred recently in the Caribbean, including Puerto Rico, the U.S. Virgin Islands, Cuba, and Central America. Cases have also been imported via tourists returning from areas with widespread dengue, including Tahiti, Singapore, the South Pacific, including the Philippines, Southeast Asia, the West Indies, India, and the Middle East . Dengue is now the leading cause of acute febrile illness in U.S. travelers returning from the Caribbean, South America, and Asia.
- From January to July 2017, Sri Lanka reported 80,732 cases of dengue fever, with 215 deaths.
- New Delhi, India, reported an outbreak of dengue fever, with 1,872 testings positive for the illness in September 2015.
- In American Samoa, there were 370 cases of dengue reported from May 2015 to Sept. 2, 2015, and 133 were hospitalized.
- Thailand reported the worst dengue virus outbreak in 20 years, with 126 deaths and 135,344 people infected with the virus, in October 2013.
- In 2011, Bolivia, Brazil, Columbia, Costa Rica, El Salvador, Honduras, Mexico, Peru, Puerto Rico, and Venezuela reported a large number of dengue cases. Paraguay reported a dengue fever outbreak in 2011, the worst since 2007. Hospitals were overcrowded, and patients had elective surgeries canceled due to the outbreak.
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What Is Dengue Hemorrhagic Fever
Serious cases of dengue will progress into dengue hemorrhagic fever or DHF. While dengue is generally flu-like DHF can be fatal.
Early symptoms are the same as dengue. But, acute symptoms are more serious. The virus causes leaky blood vessels, circulatory failure, shock and death.
There is no cure for dengue nor dengue hemorrhagic fever.
Dengue Vaccine Objectives And Challenges
Several DENV vaccines are currently under development, including some in phase 3 safety and efficacy testing . These include inactivated, live attenuated, recombinant subunit, viral vectored, and DNA vaccines. Dengue vaccine development has focused on eliciting a neutralizing antibody response, as T cells are assumed to play a minor or secondary role in dengue vaccine-mediated protection. The WHO has published guidelines on the clinical evaluation of dengue vaccines in endemic areas and on the quality, safety, and efficacy of live attenuated dengue vaccines .
Table 7.1. Vaccines in development
|Acambis/Sanofi Pasteur||Phase 3|
Finally, live attenuated vaccines must be evaluated for neurovirulence in nonhuman primates although testing a rodent model may be sufficient in the future . Neurovirulence testing is particularly important for vaccines created using the YF 17D backbone, as that vaccine has been associated with neurotropic disease .
Sophie Yacoub, Jeremy Farrar, in, 2014
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Dengue Burden In India
The disease burden is staggering as revealed by a 2014 study conducted by the National Institute of Health and Family Welfare , New Delhi. The study found that the annual average clinically diagnosed dengue cases in India was almost 6 million, or 282 times the annual reported number during 2006-2012.
Overview Of The Disease
Dengue is the second most commonly identified cause of fever in unwell international travellers. It is due to infection with a virus called dengue virus.
Dengue virus is spread by the bite of infected mosquitoes. The mosquitoes are usually of the species Aedes aegypti, and can be recognised by the white stripes on their legs. They mainly bite during the day.
Dengue is widespread throughout the tropics and subtropics, occurring in more than 120 countries.
- Nearly 100 million cases of dengue are thought to occur every year.
- Severe infection mainly affects infants and children living in the tropics and subtropics.
- Outbreaks of dengue are common and often occur in a seasonal pattern.
- Outbreaks due to imported infection have been reported in Southern Europe.
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Key Points About Dengue Fever
|See your doctor if you are unwell after travel to a dengue-affected area, or call Healthline on 0800 611 116 for advice.|
Scientists Discover How Dengue Vaccine Fails To Protect Against Disease
UNC School of Medicine scientists led by Aravinda de Silva, PhD, identified the small subpopulation of antibodies in vaccinated children that correlate with protection against dengue fever. This research should help shape better vaccines for one of the most widespread infectious diseases in the world.
CHAPEL HILL, NC Developing a viable vaccine against dengue virus has proved difficult because the pathogen is actually four different virus types, or serotypes. Unless a vaccine protects against all four, a vaccine can wind up doing more harm than good.
To help vaccine developers overcome this hurdle, the UNC School of Medicine lab of Aravinda de Silva, PhD, professor in the UNC Department of Microbiology and Immunology, investigated samples from children enrolled in a dengue vaccine trial to identify the specific kinds of antibody responses that correlate with protection against dengue virus disease. In doing so, the researchers discovered that a small subpopulation of antibodies binding to unique sites on each serotype are linked to protection. The research, published in the Journal of Clinical Investigation, provides important information for vaccine developers to consider when creating a dengue vaccine, which has long eluded scientists.
Experiments led by Sandra Henein, research associate in the UNC Department of Microbiology and
The National Institute of Allergy and Infectious Diseases funded this work through R01 grants AI107731 and AI125198.
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Cheap Fast Test For Zika And Dengue Could Cost Just $1
This paper, what it does, it shows for the first time the narrow range of antibody concentrations that actually produces enhancement of disease in vivo, said Vasilakis, who was not involved in the study. I have bias against ADE in general, but this is a very good study.
The work was published in the journal Science.
Where Is Dengue Fever A Concern
- Dengue fever is found throughout the world, but mainly occurs in tropical and subtropical areas.
- It is widespread in regions of Africa, Central and South America, the Caribbean, the Eastern Mediterranean, South and Southeast Asia, and Oceania.
- The World Health Organization estimates that over 40% of the worlds population live in areas where dengue viruses can be transmitted.
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Status Of Vaccine Development
The first dengue vaccine, Dengvaxia by Sanofi Pasteur, was first registered in Mexico in December, 2015. CYD-TDV is a live recombinant tetravalent dengue vaccine that has been evaluated as a 3-dose series on a 0/6/12 month schedule in Phase III clinical studies. It has been registered for use in individuals 9-45 years of age living in endemic areas.
There are approximately five additional vaccine candidates under evaluation in clinical trials, including other live-attenuated vaccines, as well as subunit, DNA and purified inactivated vaccine candidates. Additional technological approaches, such as virus-vectored and VLP-based vaccines, are under evaluation in preclinical studies.
The growing global epidemic of dengue is of mounting concern, and a safe and effective vaccine is urgently needed. WHO expects vaccines to be an integrated part of the Global dengue prevention and control strategy .
Fortunately There Is Now A Vaccine For Dengue
|12-45 years||Dengvaxia is indicated for the prevention of dengue disease caused by dengue virus serotypes 1, 2, 3 and 4 in individuals 12 to 45 years of age living in enedmic areass.|
|3-dose schedule||The vaccination schedule consists of three injections of 0.5ml to be administered subcutaneously at 6 months intervals|
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How Can I Prevent Dengue Fever
As a mosquito-borne disease, preventing dengue is as simple as preventing mosquito bites. There is no approved dengue vaccine in Canada.
Many health organizations suggest the following to protect yourself from dengue:
- Wear long-sleeve shirts and long pants.
- Treat clothes with repellents like permethrin.
- Use EPA-registered mosquito repellent like DEET.
- Consider using mosquito netting if you will be in an areas with many mosquitoes.
- Make sure windows and doors screens are closed to avoid allowing mosquitoes into inclosed spaces.
- Avoid areas with standing water. Especially at times of high mosquito activity like dawn and dusk.
Paspsort Health locations carry kits specifically designed to help prevent mosquito bites and mosquito-borne disease. Be sure to take one with you on your next trip.
For more information on mosquito bite prevention methods and what you can do to protect yourself and your family, speak with a travel health specialist by calling or booking online today.
Protect Against Mosquito Bites Indoors
- Use screens on doors and windows.
- Use insect sprays.
- Use mosquito coils.
- Use a mosquito net over your bed at night. New bed nets often have insecticide already on the net but, if not, you can spray the net with insecticide.
- Turn on air conditioning if you have it and close all windows and doors this is very effective at keeping mosquitoes out of the room.
The dengue-carrying mosquito can be around during the day so keep covered day and night.
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How Dengue Is Spread
Dengue is spread by infected mosquitoes, usually the Aedes aegypti and Aedes albopictus varieties.
These mosquitoes bite during the day, usually early in the morning or in the early evening before dusk.
They’re often found near still water in built-up areas, such as in wells, water storage tanks or in old car tyres.
Dengue isn’t spread from person to person.
There are four types of the dengue virus. You can get it again if you’ve had it before, as you’ll only be immune to one type of the virus.
What Are The Symptoms
- The symptoms most commonly appear three to fourteen days after being bitten by an infected mosquito.
- They usually include flu-like symptoms such as high fever, severe headache, pain behind the eyes, joint and muscle pain, nausea, vomiting and a rash.
- It is common for some people to show no symptoms and most people recover from dengue fever after a few days.
- In a small percentage of cases, people with dengue fever develop dengue haemorrhagic fever, also known as severe dengue. Warning signs usually occur three to seven days after the first symptoms, and include a decrease in fever, bleeding from nose or gums, fatigue, severe abdominal pain, persistent vomiting and difficulty breathing.
- Children growing up in risk areas are at a higher risk of severe dengue.
- Severe dengue can lead to shock. With proper medical care, almost all cases will survive.
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How Is Dengue Fever Prevented
For most travellers, there is no suitable vaccine to prevent dengue. The best way to avoid infection in areas where there are dengue-carrying mosquito populations is to protect yourself against being bitten and to reduce potential mosquito breeding sites. All people in dengue-affected areas, whether you have been previously infected or not, should take precautions to prevent being bitten.A new vaccine for dengue has been approved in some countries where dengue fever is common. It is only useful for people who have previously been infected with dengue fever, as it can actually increase the risk of severe dengue for people who have never had the disease before. This vaccine is not routinely available in New Zealand. Please see your local travel medicine specialist for further advice.
What Is The Dengue Fever Vaccine
Dengue fever vaccines are designed to prevent the spread of the dengue virus through mosquitoes or other means. About five dengue vaccines are under development. But, one has been approved for use in Mexico and Brazil.
Dengvaxia® is the first dengue vaccine approved for use in the prevention of dengue. It is set to come to market in Brazil and Mexico soon. There is no word yet on when it or another dengue vaccine will be available in the United States.
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What Is The Role Of Vaccination In The Prevention Of Dengue
One vaccine is currently approved for the prevention of dengue infection. Sanofi Pasteur registered Dengvaxia , a live recombinant tetravalent vaccine, in several countries in late 2015-2016, with Mexico being the initial country to register the vaccine in December 2015. The vaccine is given in 3 doses at age 0, 6, and 12 months. It underwent testing in more than 30,000 volunteers and was shown to reduce the risk of severe illness and hospitalization by as much as 30% in individuals previously infected with one or more strains. The vaccine proved less effective in persons who were not previously exposed to dengue and in areas with a lower burden of disease. Owing to concern that the vaccine may act like an initial dengue infection in this second group of individuals not previously infected with the virus, with additional exposure to a second serotype placing these individuals at increased risk of severe dengue, the WHO released a position paper in July 2016, stating that countries should consider introduction of vaccine as a part of an comprehensive dengue control strategy only where epidemiologic data indicate a high burden of disease.
World Health Organization. Dengue and severe dengue fact sheet. WHO. Available at . April 2017 Accessed: September 28, 2017.
Wilson ME, Chen LH. Dengue: update on epidemiology. Curr Infect Dis Rep. 2015 Jan. 17 :457. .
How Does Dengue Spread
- A mosquito bites an infected human.
- This mosquito is now infected with dengue fever. Mosquitoes are only carriers of the disease, it does not affect them as it does humans.
- The mosquito bites a human. That human is now infected with the virus. He or she will then infect any unaffected mosquitoes that bite them.
According to the PHAC, about 75 percent of all dengue infections show no symptoms. Around 20 percent of dengue symptoms are mild. But, five percent will develop severe, life-threatening symptoms.
Be sure to use repellents and nettings to avoid mosquito bites.
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What Tests Do Health Care Providers Use To Diagnose Dengue Fever
Medical professionals usually make a diagnosis of dengue fever infection when a patient exhibits the typical clinical symptoms and signs of headache, high fever, eye pain, severe muscle aches, and petechial rash and has a history of being in an area where dengue fever is endemic. Dengue fever can be difficult to diagnose because its symptoms overlap with those of many other viral illnesses and tropical diseases, such as the West Nile virus and chikungunya fever.
Health care professionals may use a blood test called the DENV Detect IgM Capture ELISA to diagnose people with dengue fever. The FDA notes that the test may also give a positive result when a person has a closely related virus, such as West Nile disease.
Impediments In Developing A Dengue Vaccine
Several dengue vaccine candidates have been under development over the past few decades, but none have been successful, until now. The difficulty in developing a dengue vaccine stems from the fact that there are four kinds of dengue virus that circulate, of which one type predominates in a particular dengue season.
Weakening the virus by chemical treatments so that it does not cause disease, yet is still strong enough to stimulate the immune system to generate a protective immune response is very tricky, especially since there are four serotypes that require equal levels of attenuation.This problem has been solved in the new dengue vaccine developed by Sanofi Pasteur.
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