New Approach for Dengue Vaccine

New Approach for Dengue Vaccine
Categories: News

A study published by researchers at the Perelman School of Medicine at the University of Pennsylvania suggests an entirely new approach to vaccines - creating immunity without vaccination.

The concept outlined in a study published in Scientific Reports shows that an animal injected with a synthetically engineered DNA that contains a specific neutralizing antibody was able to produce the exact antibody necessary to protect against the Dengue virus. This approach, labelled as DMAb, worked within a week of administration and without the need for standard antigen-based vaccination.

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With nearly 400 million Dengue infections each year, the potentially lethal virus is a dangerous mosquito-borne viral infection, risk of which has grown in recent decades. The geographical reach of dengue has expanded to include over 100 countries, resulting in a significant health and economic burden worldwide.

Although vaccines are being developed to fight dengue virus, none are currently available that provide protection against all four dengue viral serotypes. Once an individual develops protection against one serotype that they were infected with, it leaves them vulnerable to the other Dengue serotypes.

Antibodies have two important areas: one end, known as the variable region, recognizes target proteins, such as those on the surface of a dengue virus particle. The other end, known as the constant region, binds to receptors on the surface of cells that can direct the immune system to respond in a variety of ways.

The dengue virus uses this natural process to its advantage: the cells that recognize the constant region of an antibody are the exact cells dengue virus prefers to infect. When low levels of antibodies from a previous dengue infection sense a new serotype is around, they weakly bind to the different serotype, lead it to cells with receptors for their constant regions, and the new serotype ultimately enters those cells. The Dengue virus can then infect these cells, leading to greater levels of virus production and enhanced, sometimes lethal, disease.

In the current study, the DNA used to encode the neutralizing antibodies against dengue virus was altered to produce a neutralizing antibody that does not bind to cell receptors, effectively eliminating the chance for dengue infection to lead to enhanced, lethal disease.

“Engineering novel methods of delivering monoclonal antibodies could be an important approach in the fight against infection and in unique treatment situations," said David B. Weiner, PhD, a professor of Pathology and Laboratory Medicine. “We can produce a synthetic immune response by encoding an antibody and delivering it as a non-live, non-viral, non-permanent antibody."

The next step will be to demonstrate that this new method is effective with larger animals and eventually humans. This new approach also opens up a vista of new possibilities it could potentially be used to protect against or treat other diseases.

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