Dengue vaccine

Dengue is a viral infection caused by the dengue virus (DENV), spread through the bite of an infected mosquito. Large outbreaks tend to happen every 3-4 years. Around 80% of cases occur in the Americas.

Currently, there is one vaccine licensed in the UK (Qdenga), and another that is licensed in various other countries (Dengvaxia). Qdenga is licensed in the UK for use in individuals aged over 4, and Dengvaxia is used in individuals aged 9-45. Both vaccines protect against the four types of DENV; DENV1, DENV2, DENV3, and DENV4. However, in the UK, it is only recommended  for people who have had a confirmed dengue infection in the past. In some countries, population surveys may be carried out to find areas where over 80% of individuals have had previous infection. In these areas, mass vaccination without prior testing may be considered.

Both vaccines are live attenuated vaccines. This means they contain a weakened strain of the live virus, therefore are not suitable for some people. For example, those with weekend immune systems.   

In the UK, Qdenga is a licensed vaccine for individuals aged over four years. It is delivered in a two-dose schedule. Recommendations for who should receive the vaccine vary in different countries.

The Joint Committee on Vaccination and Immunisation (JCVI) recommended that the vaccine could be offered to individuals aged four years of age and older, with confirmed dengue infection in the past, who are either: 

• planning to travel to areas where there is a risk of dengue infection or areas with an ongoing outbreak of dengue 
• are exposed to dengue virus through their work, for example, laboratory staff working with the virus  

Guidance is being developed with the UK Health Security Agency (UKHSA) Rare and Imported Pathogens Laboratory on best practices for investigating possible previous dengue infection. Visit NaTHNaC for more information.

Globally, Dengvaxia (CYD-TDV) was the first dengue vaccine to be licensed. It has been used in Mexico since 2015 in individuals aged 9-45 who have had dengue before, in areas where dengue is common. It is currently used in various countries globally. It is delivered as a three-dose schedule, six months apart.

As both of these vaccines contain weakened live strains of the virus, they should not be given to those with weakened immune systems. They should also not be given to pregnant or breastfeeding people, or people who are allergic to any of the ingredients.

Side effects for Qdenga include:

Very common (may affect more than 1 in 10 people):

• injection site pain or redness
• headache
• muscle pain
• generally feeling unwell
• weakness
• infections of the nose or throat
• fever

Common (may affect up to 1 in 10 people):

• injection site swelling, bruising, or itching
• pain or inflammation of the nose or throat
• joint pain
• flu-like symptoms

Uncommon (may affect up to 1 in 100 people):

• diarrhoea
• feeling sick or being sick
• stomach pain
• injection site bleeding or changes in colour
• feeling lightheaded
• itchy skin, or skin rash
• tiredness
• inflammation of the airways
• runny nose

Very rare (may affect up to 1 in 10,000 people):

• rapid swelling under the skin in areas such as the face, throat, arms and legs

Side effects for Dengvaxia include:

Very common: (may affect more than 1 in 10 people)

• • headache
  • muscle pain 
  • generally feeling unwell
  • weakness
  • injection site reactions: pain and redness 
  • fever.

Common: (may affect up to 1 in 10 people)

• injection site reactions: bruising, swelling, and itching.

Uncommon: (may affect up to 1 in 100 people)

• infections of the nose or throat 
• pain or swelling of the nose or throat
• feeling dizzy
• sore throat
• cough
• feeling sick.

As with any vaccine, medicine or food, there is a very small chance of a severe allergic reaction (anaphylaxis). Anaphylaxis is different from less severe allergic reactions because it causes life-threatening breathing and/or circulation problems. It is always extremely serious but can be treated with adrenaline. Healthcare workers who give vaccines know how to do this.

In the UK between 1997 and 2003 there were a total of 130 reports of anaphylaxis following ALL immunisations. Around 117 million doses of vaccines were given in the UK during this period. This means that the overall rate of anaphylaxis is around 1 in 900,000.

If you are concerned about any reactions that occur after vaccination, consult your doctor. In the UK you can report suspected vaccine side effects to the Medicines and Healthcare products Regulatory Agency (MHRA) through the Yellow Card Scheme.

You can also contact the MHRA to ask for data on Yellow Card reports for individual vaccines. See more information on the Yellow Card scheme and monitoring of vaccine safety.

Other than the active ingredients, Qdenga contains:

• A,α-Trehalose dihydrate – a type of sugar often used as a stabiliser
• Poloxamer 407 – often used to stabilise the vaccine ingredients
• Human serum albumin – proteins that protect the active ingredients
• Potassium dihydrogen phosphate and disodium hydrogen phosphate – to maintain the pH of the vaccine solution
• Potassium chloride and sodium chloride – salts act as adjuvants, strengthening and lengthening the immune response to the vaccine
• Water

Other than the active ingredients, Dengvaxia contains

• Amino acids including phenylalanine and arginine hydrochloride – support the production of proteins that help create an immune response.
• Sucrose, trometamol, urea - often used as a stabilisers
• Trehalose dihydrate – often used to maintain the pH of a solution
• Sorbitol (E420) – often used as a stabiliser or a bulking agent
• Sodium chloride - Salts act as adjuvants, strengthening and lengthening the immune response to the vaccine
• Water
• Hydrochloric acid and sodium hydroxide for pH adjustment.

Why are dengue vaccines only available for those with previous dengue infection in the UK?

There are four types of dengue virus; DENV1, DENV2, DENV3, and DENV4. When someone becomes infected, they are infected by one type of dengue, and lifelong immunity against that specific type of DENV is often developed. However, individuals are left vulnerable to the other three types, so it is common to become infected more than once.

Unfortunately, the second infection is often worse than the first. This is because of a process called antibody-dependent enhancement (ADE). Normally, our immune system remembers infections and fights them off better the next time. But with dengue, if you get infected with a different type of the virus, ADE can make it worse.

Instead of stopping the virus, antibodies from the first infection can help the new virus enter immune cells, rather than stopping them. This makes the infection worse. The infection spike triggers a strong immune response called a cytokine storm. Cytokines are small proteins that help the immune system by telling the immune system that there is an infection. But this response can be too strong, and cause bleeding or organ failure.

Therefore, there is a theoretical risk of severe dengue if a person with no prior dengue infection receives the vaccine and is then infected with a dengue virus in the future. Hence the requirement of a confirmed dengue infection in the past for those receiving the vaccine in the UK.

Read more about second dengue infections here.

Mass vaccination without individual screening

Around the world, some countries carry out mass vaccination programmes without individual screening for previous dengue infection. The rationale behind this is that vaccinating individuals in areas where a large proportion of the population already has antibodies against dengue from natural infection would result in the prevention of a larger number of severe dengue cases.

Prior to implementing a mass vaccination programme, a population survey would be carried out to identify areas where previous infection levels are high in the age group that would be targeted for vaccination.  Some places that have high levels of previous infection, where at least 80% of children aged 9 years have had previous infection, may consider to implement a mass programme rather than individually screening before vaccination.  The World Health Organization explain that communication is important to openly discuss the risks of vaccinating people whose immune status is unknown.

Source: The World Health Organization