Dengue vaccines in India: A look at the ongoing trials and development

Subject : Science and technology

Section: Health

Context:

With the expanding geography of dengue infections — in India as well as the world — an increasing need has been felt for an effective vaccine that can protect against all four serotypes. Nearly half the population of the world lives at risk of the disease at present.

Dengue cases all across India:

The disease in India has spread from just eight states and union territories in 2001 to all states by 2022 — Ladakh is the latest among states/UTs to report dengue cases.
Efforts are ongoing within the country to develop an effective vaccine against the mosquito-borne disease that can lead to internal bleeding, circulatory shock, and death.

Vaccine in human trials

At present, there are three vaccine candidates that are being tested in humans in India.

A vaccine developed by Panacea Biotec based on live weakened versions of the four dengue serotypes developed by the National Institute of Allergy and Infectious Diseases in the United States.
- They deleted parts of the genetic code of DENV1, DENV3, and DENV4 serotypes of the virus and then genetically engineered DENV2 backbone using parts from weakened DENV 4 on which the others were tacked on.
- These were grown in cell culture by Panacea Biotec to develop the vaccine.
A second vaccine candidate was developed by the Serum Institute of India with the same weakened virus from the United States.
The same technology has also been used by Indian Immunologicals Limited to develop the vaccine.

Challenges in vaccine development:

One of the main challenges is antibody-dependent enhancement (ADE) — a person with low levels of antibodies against one serotype of dengue, may end up getting a more severe infection with another serotype of dengue.
This was what led to controversy surrounding the first dengue vaccine to be approved.
Only after a vaccination programme had been rolled out in the Philippines, it was found that the vaccine could actually increase the risk of severe disease in people who had not been infected before.

Solution to this problem:

To do away with this problem, both the Indian research teams selected a specific part of the envelope protein known to not cause ADE.
The team from the International Centre for Genetic Engineering and Biotechnology (ICGEB) created a Virus-Like Particle using these parts of the virus.
- The vaccine was developed in collaboration with Sun Pharmaceuticals.

The other team from Tata Institute of Fundamental Research and Rajiv Gandhi Centre for Biotechnology among other institutes again used the same envelope parts of the four dengue viruses along with another part called non-structural-1 and constructed a genetic sequence out of it.
- This resulted in a DNA vaccine with all four serotypes.
  - Although DNA vaccines can be manufactured at lower safety levels, at a lesser cost, and can be stored even at room temperatures, they don’t always produce a very good immune response.
- The researchers are currently optimizing the vaccine using nano-plasmids.