Why don’t we have a safe and effective dengue vaccine yet

While the plunge in COVID-19 cases is something that has helped people take a sigh of relief, the incessant rise in the number of dengue cases has alarmed doctors and healthcare professionals across countries. Not only are we experiencing a huge spike in the number of cases, but it seems that the associated symptoms are only getting worse, given the onset of new strains.

At such a time, dengue vaccine would surely have been a saviour. However, there's still a long way to go. Why is it so? Let us find out.

Read more: Dengue fever: Signs your dengue infection is turning severe

Dengue is a mosquito-borne viral illness caused by the dengue virus. Prevalent in tropical environments, the viral infection is transmitted by female mosquitoes mainly of the species Aedes aegypti and, to a lesser extent, Ae. albopictus, and is caused by the dengue virus called DENV.

While most dengue infections are mild and can be managed at home, if left untreated and unattended to, it can develop into something called severe dengue, a potentially lethal complication, as per the World Health Organization (WHO). Given that dengue belongs to the Flaviviridae family, there are four distinct serotypes of the virus called DENV-1, DENV-2, DENV-3 and DENV-4 that cause dengue. Out of all the strains, DENV 2 or the strain D2 is considered to be the most severe and can even lead to fatal internal bleeding and shock.

There has been a staggering increase in the number of dengue infections in India, including in states like Kerala, Telangana, Maharashtra, Uttar Pradesh and Odisha. With the monsoons and the seasonal changes having contributed to the uptick of infections, this year, the numbers associated with mosquito-borne illnesses have surged considerably.

Healthy officials suggest that the DENV-2, or the strain D2 of the four serotypes of dengue virus, is what is causing the sudden rise in the number of cases and also leading to severity. Apart from being more virulent, experts believe that the new strain can trigger high grade fever, vomiting, joint pains, altered sensorium and may even lead to lethal complications resulting in dengue hemorrhagic fever and dengue shock syndrome.

Dengue symptoms can range from mild to moderate and in some cases, it can also cause severe complications. However, it can be well managed at home.

Given that prevention is better than cure, a dengue infection can also be prevented effectively, with proper measures. Apart from practicing good hygiene, one must remember to clean and disinfect standing water sources and avoid water stagnation. Wear full length clothes and apply mosquito repellants when needed.

Read more: Doctors warn dengue’s new D2 strain can lead to high-grade fever and shock syndrome; how to stay safe

When it comes to dengue, taking preventive, precautionary measures is of utmost importance. However, unlike a flu shot or a COVID-19 vaccine, we still do not have a safe and effective vaccine against dengue.

Although there is a dengue vaccine called Dengvaxia (CYD-TDV), which is the first vaccine against dengue, licensed in 2015 and available in some countries for people aged 9 to 45 years, the WHO recommends that the vaccine be given only to people with confirmed previous dengue virus infection.

As per the Centre for Disease Control and Prevention, "The vaccine manufacturer, Sanofi Pasteur, announced in 2017 that people who receive the vaccine and have not been previously infected with a dengue virus may be at risk of developing severe dengue if they get dengue after being vaccinated. "

The dengue virus consists of four serotypes, DENV-1, DENV-2, DENV-3 and DENV-4. The available vaccine only provides immunity against one serotype, which does not generate lasting immunity against the other three, making it only less effective.

Now, when it comes to safety, experts suggest that being infected with or developing immunizing antibodies against one viral serotype would lead to the patient having more severe infections from a different serotype, something known as antibody-dependent enhancement. As per the WHO, "It carries an increased risk of severe dengue in those who experience their first natural dengue infection after vaccination (those who were seronegative at the time of vaccination)."

Recent reports suggest that Indian scientists from the National Centre for Biological Sciences (NCBS)-Tata Institute of Fundamental Research in Bengaluru, have developed a DNA vaccine candidate against the dengue virus.

The researchers selected a part of the most important viral protein called EDIII from all the four serotypes of the virus. They also selected the NS1 protein from the DENV2 serotype, known to cause severe dengue.

The study published in MedRxiv titled 'Immune profile and responses of a novel Dengue DNA vaccine encoding EDIII-NS1 consensus design based on Indo-African sequences' lays down the key problems faced by the scientists in developing a dengue vaccine.

The author of the study, Dr Arun Sankaradoss said, “In the traditional vaccines, the whole envelope protein is used, which can lead to Antibody Dependent Enhancement -- ADE (where the viral antigen binds to less-effective antibodies making the virus more effective)."

“We have used only the domain III of the envelope protein from all four serotypes to avoid ADE. We have added the NS1 protein that is known to generate both T cell and B cell response,” he adds.

Prof Sudhir Krishna, senior author and anchor of the dengue vaccine development programme at NCBS in Bengaluru, explains by saying, “We know there are four serotypes of the virus, but what we found was that there were genetic variations within the serotypes. Any sequence with over 6 percent difference is considered to be a different genotype. The team created a consensus sequence that is the same across genotypes as well.”

Furthermore, he emphasizes on the need for more collaborations, "to bring teams across India to work together, including the Translational Health Science and Technology Institute (THSTI), Rajiv Gandhi Centre for Biotechnology and NIMHANS."