Journal Science: Dengue Vaccine Is Currently Being Made!

A permanent solution for Dengue maybe in the offering. Researchers at Vanderbilt University and the National University of Singapore teamed up and found an effective human monoclonal antibody which can strongly neutralize a type of the potentially lethal dengue virus. The finding, which was published in Journal Science, could pave the way to completely eradicate this life-threatening Dengue virus – which is a complex of four distinct but related mosquito-borne viruses.

“Scientists in the antibody discovery group of the Vanderbilt Vaccine Centre continue to make great strides in developing novel antiviral drugs, such as this human antibody that not only kills dengue virus but also prevents enhanced dengue disease,” said co-corresponding author James Crowe Jr.

The deadly disease referred to as ‘breakbone’ fever infects around 390 million people a year.Dengue is transmitted by several species of mosquito within the genus Aedes, principally A. aegypti. These mosquitoes usually live between the latitudes of 35° North and 35° South below an elevation of 1,000 metres (3,300 ft) and typically bite during the day – particularly in the early morning and in the evening.

The virus has five different types infection with one type usually gives lifelong immunity to that type, but only short-term immunity to the others. The four “serotypes” of dengue are distinguished by different antigens, or proteins on the viral envelope that elicit immune responses.

Frighteningly, dengue can be transmitted via infected blood products and through organ donation.In countries such as Singapore, where dengue is endemic, the risk is estimated to be between 1.6 and 6 per 10,000 transfusions. The new vaccine could help curb this risk of contracting Dengue.

What makes dengue so challenging, and so hazardous, is that antibodies generated against one serotype do not protect against the others.

In fact, they actually can enhance infection by a second serotype, a process known as antibody-dependent enhancement (ADE) of infection. Therefore, sequential infections increase the risk for dengue hemorrhagic fever and dengue shock syndrome, characterized by fever, vomiting, internal bleeding and potentially fatal circulatory collapse.

The researchers previously generated human monoclonal antibodies in the lab against a complex epitope, or antigenic portion of the viral envelope. In the current study, researchers they used cryo-electron microscopy to freeze samples at very low temperatures so they could visualize antibody-antigen binding almost down to the atomic level. In this way they were able to identify a human monoclonal antibody against dengue virus type 2 (DENV2) that “locked” across an array of envelope proteins. In a mouse model, this prevented the virus from fusing to its target cell, thus it prevents infection.

The antibody also was remarkable in that it has a second major function – it blocks the binding of the other class of antibodies that otherwise would enhance infection.

This specific “epitope,” or portion of the envelope proteins elicits a specific immune response, thus it is a potential target for the development of dengue vaccines and therapeutics, researchers said.

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