BENGALURU: Indian Institute of Science (IISc) researchers have found that an interdependence between the dengue virus and the immunity of the human population is increasing severity of dengue infections – caused by the virus borne by Aedes aegypti mosquito – and posing challenges in developing an effective vaccine in India.
The researchers found that while antibodies are generated within the human body after an initial infection and protect against infections from other serotypes of dengue, these fade over time.
Rahul Roy, Associate Professor at the Department of Chemical Engineering (CE), IISc, and Suraj Jagtap, PhD student at CE, explained that at any given time, several strains of each serotype exist in the viral population. The antibodies generated in the human body after a primary infection provide complete protection from all serotypes (categories) for about 2-3 years. Over time, however, the antibody levels begin to drop, and cross-serotype protection is lost.
The researchers propose that if the body is infected around this time by a similar – not identical – viral strain, then Antibody Dependent Enhancement (ADE) kicks in, giving a huge advantage to the new strain, causing it to become the dominant strain in the population. Such an advantage lasts for a few more years, after which the antibody levels become too low to continue providing protection.
“People might be infected first with one serotype and then develop a secondary infection with a different serotype, leading to more severe symptoms. We believe that if the second serotype is similar to the first, the antibodies in the host’s blood generated after the first infection bind to the new serotype as well as to immune cells called macrophages. This allows the newcomer to infect macrophages, making the infection more severe,” Jagtap said.
There are four broad serotypes of the dengue virus (Dengue 1, 2, 3 and 4). Using computational analysis, the team examined how much each of these serotypes deviated from their ancestral sequence, from each other, and from other global sequences. “We found that the sequences are changing in a very complex fashion,” Roy said.
Cases of dengue have steadily increased in the last 50 years, predominantly in the South-East Asian counties. And yet, there are no approved vaccines against dengue in India, although some vaccines have been developed in other countries. “We were trying to understand how different the Indian variants are, and we found that they are very different from the original strains used to develop the vaccines,” said Roy.
The IISc scientists examined 408 genetic sequences of Indian dengue strains from infected patients collected between the years 1956 and 2018 for this research, according to an IISc release.