Dengue infection is a mosquito-borne disease having single positive-stranded RNA virus. Five serotypes of the virus have been found, all of which can cause the full spectrum of disease.
About 2.5-3 billion people (approximately 40%-50% of the world’s population) are estimated to be at risk of dengue infection. There is a serious dengue problem worldwide and it’s more prevalent in South East Asia. Pakistan is also facing a dire situation in this regard. Therefore, we need a vaccine as soon as possible. A vaccine by definition focuses on preventing people from a disease they were not exposed to before.
There are 4 serotypes of dengue infection. A vaccine (Dengvaxia) was introduced to counter all these 4 types of Dengue and was called as a tetravalent vaccine. This vaccine provided a chance for cross protection between all the 4 types.
A point to understand here is that, if a person gets the type 1 infection, then the vaccine introduced in the body enables them to produce antibodies that protect against further infection by type 1 dengue infection. This is called homotypic immunity to dengue 1. This homotypic immunity to type 1 may give protection from infection of dengue 2, 3 and 4 for a short period of time after which such cross protection does not remain much effective. In fact, the antibodies produced, stop protecting the body and start spreading the infection. This is called antibody dependent enhancement or ADE which plays a key role in the onset of Dengue infection.
Due to the ADE phenomenon, it is a challenge to manufacture a suitable vaccine for Dengue. This is because when the dengue virus infects the human body it creates two kinds of antibodies. One type is the good antibodies, or neutralizing antibodies, that stop the disease.
The other type, the enhancing antibodies, is involved in ADE and helps spread the disease. The dengue virus on infection makes more of the second type. Similarly, the live but weakened viral vaccines also created these two types of antibodies. The enhancing antibodies do not distinguish between serotypes whereas the disease-protecting ones work only on their particular serotype.
Dengvaxia (a tetravalent vaccine against Dengue) is a mixture of four live attenuated viruses. The ideal scenario for a tetravalent vaccine – one with four antigens – is that the immune system recognizes all four viruses and produces antibodies to all of them. Unfortunately, Dengvaxia came out to be physically tetravalent and functionally monovalent, giving only partial immunity against Dengue infection. Thus due to these recent shortcomings, Dengvaxia is not sold on the market and is still undergoing trials.
A recent research in molecular biology aimed at producing a vaccine which would induce a protective response against all four stereotypes and ensure that severe dengue is not caused by the vaccine. At present, a team led by the Walter Reed Army Institute of Research has gained new insights into the mechanism of vaccine-induced T cell immunity. Their main thesis is based on the view point that,
“Healthy T cell response may be an important part of immunity to dengue and viral diseases.”
Their study employed samples from a clinical trial for another live-attenuated tetravalent dengue vaccine called TAK-003.
The TAK-003, developed to protect against all four serotypes, has been shown to be safe and immunogenic in small animal models and non-human primates. They focused thorough study into the regulation, gene expression and metabolic pathways of T cells, along with the discovery of a marker, transferrin receptor 1 (TfR1) which showed that T cell immunity is dependent on the availability of specific metabolites.
Collaborative efforts with partner programs suggests that targeting the unique metabolic requirements of the immune cells is thought to provide protection from dengue infection and that it may contribute in the establishment of protective immunity following vaccination. This approach involving T cells (the mainstream immunity providers of the body) may prove valuable in the course of achieving a potent vaccine as it aims altering the genetic regulation and metabolism of T cells.
As the Dengue Vaccine Programs throughout the world are striving to understand mechanisms to boost protection from the infection, there is raising hope that they will achieve their goals in due time. It is now our duty to ensure preventive measures against Dengue on our part and hope for a better vaccine to come into action and eradicate Dengue from the world forever!