More than 100,000 people, according to researchers who analyzed gene sequences collected over six decades, from 1956 to 2018,
DENV-1, DENV-2, DENV-3, and DENV-4 are four related serotypes or viral strains that cause dengue. These serotypes interact differently with antibodies, substances produced by the human body’s immune system to fight harmful, foreign substances known as antigens, making dengue difficult to control.
According to the study, an initial infection with one of the serotypes causes the body to develop antigens that can later interact negatively with another serotype to cause dengue shock syndrome or dengue hemorrhagic fever, both of which are usually fatal.
Study participant Swetha Raghavan says she and her colleague Pratik Lakhani at the National Center for Biological Sciences are developing an mRNA vaccine candidate for clinical trials as an alternative to existing Dengue vaccines.
Current dengue vaccines use live attenuated versions of the four serotypes of the dengue virus, while mRNA vaccines work by “teaching” cells how to make copies of viral proteins so the body can recognize and fight future infections.
Also, according to the study, “current vaccines are based on older dengue isolates from outside South Asia, and it is unclear whether they will work against dengue viruses circulating in India.”
mRNA: Key to Dengue Vaccine Production
Raghavan explains: “Our attempt to develop a vaccine for India is looking at nucleic acid-based approaches (mRNA) as a viable alternative, and the genome sequence data from the study is playing an important role.”
Several genotypes have become widespread in India since 2000, according to a study published in April in the journal PLOS Pathogens. Genotype is the genetic makeup of an organism and refers to the specific information contained at a particular location in its genomic sequence.
The most common 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, while some types, such as DENV4-Id, are country-specific.
Although primary infection with any DENV serotype usually results in mild flu-like symptoms and lifelong immunity to that specific serotype, numerous epidemiological studies have shown that infection with different serotypes can lead to dengue shock syndrome or dengue hemorrhagic fever through a process known to be antibody-dependent. Improvement (ADE).
According to Lakhani, during secondary infection, the body’s antibodies against the first serotype do not neutralize the secondary serotype.
Antibodies that can form a vaccine
“Antibodies are not present in optimal concentrations, but not neutralizing, they contribute to increased uptake of non-neutralized DENV, which is called ADE,” says Lakhani.
“Antibodies are not present in optimal concentrations, but they are not neutralizing, they promote more absorption of non-neutralized DENV, which is called ADE,” says Lakhani.
According to the study, some vaccine candidates, while not offering adequate protection against dengue infection, may lead to disease exacerbations through ADEs during future infection.
According to Lakhani, immunity lasts only two or three years, after which ADE may develop, while primary or primary infection confers cross-protection against other serotypes.
“DENV4 ID has now become the predominant serotype in South India,” said Lakhani. “It has evolved to become more closely related to DENV1 and DENV3.
“If the newly emerging DENV4 Id strain in India is the cause of the secondary infection, then it could lead to severe disease transmission.”
According to the study, at least 50% of infections in South India now have the DENV4 Id lineage.
Gautam Menon, dean of the department of physics and biology at Ashoka University, says the study “shows how genomic control can be combined with a better immunological understanding of how infection by one serotype can affect the course of subsequent infection by another.” a powerful tool for predicting public health.”
- Evolutionary dynamics of dengue virus in India – (https:journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010862)