According to the study, initial infection with one of the serotypes causes the body to develop antigens, which can subsequently interact negatively with another serotype to cause dengue shock syndrome or dengue hemorrhagic fever, both of which are usually fatal.

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Swetha Raghavan, a study participant, says she and her colleague at the National Centre for Biological Sciences, Pratik Lakhani, are preparing an mRNA vaccine candidate for clinical trials as an alternative to existing dengue vaccines.

Existing dengue vaccines use live attenuated versions of the four serotypes of the dengue virus, whereas mRNA vaccines function by ‘teaching’ cells how to create copies of viral proteins so that the body can recognize and fight off future infections.

Also, according to the study, “existing vaccines are based on old dengue isolates from outside South Asia, and it is unclear whether they will work against dengue viruses circulating in India”.

mRna: the Key to Producing Dengue Vaccine

Raghavan explains: “Our attempt at making a vaccine for India looks at nucleic acid-based approaches (mRNA) as a viable alternative, and genome sequencing data from the study plays an important role.”

In accordance to a study published in the journal PLOS Pathogens in April, a number of genotypes have been widespread in India since 2000. A genotype is an organism’s genetic composition and refers to the specific information contained at a certain place in its genomic sequence.

The Most Prevalent Genotype

The most prevalent were DENV-1 genotype III, DENV-2 cosmopolitan genotype, DENV-3 genotype III, and DENV-4 genotype I.

According to Roy, the four serotypes have temporal and regional variations in India, with some varieties, such as DENV4-Id, being unique to the country.

While primary infection with any one DENV serotype usually results in mild flu-like symptoms and lifelong immunity against that specific serotype, numerous epidemiological studies show that infection with different serotypes can cause dengue shock syndrome or dengue hemorrhagic fever via a process known as Antibody-Dependent Enhancement (ADE).

According to Lakhani, during a secondary infection, the body’s antibodies against the first serotype do not neutralize the secondary serotype.

Antibodies that Could Make-up the Vaccine

“As antibodies are present at sub-optimal concentrations but lack neutralizing ability, they aid increased uptake of the non-neutralized DENV and this is termed ADE,” says Lakhani.

“As antibodies are present at sub-optimal concentrations but lack neutralizing ability, they aid increased uptake of the non-neutralized DENV, and this is termed as ADE,” says Lakhani.

According to the study, some vaccine candidates, in addition to not offering adequate protection against dengue infection, can even lead to exacerbated disease through ADE upon future infection.

According to Lakhani, while the initial or primary infection provides cross-protection against other serotypes, the immunity only lasts two or three years, after which ADE can develop.

“DENV4 ID has now become the predominant serotype in South India,” says Lakhani. “It has evolved in such a way that it is becoming more closely related to DENV1 and DENV3.

“If DENV4 Id, the strain newly evolved in India, is the cause of secondary infection, then it can cause severe disease transmission.”

According to the study, at least 50% of infections in South India currently have the DENV4 Id lineage.

Gautam Menon, dean of the departments of physics and biology at Ashoka University, says that the study illustrates “how genomic surveillance, coupled with a better immunological understanding of how infection by one serotype can influence the course of a later infection by another, can be a powerful tool for public health forecasting.”

Reference :

1. Evolutionary dynamics of dengue virus in India – (https:journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010862)

Source: Medindia