Using part of an antibody isolated at Vanderbilt University Medical Center that “broadly neutralizes” the human dengue virus, biologists at the University of California San Diego and colleagues have disarmed the mosquito that transmits the disabling and potentially deadly tropical infection.
Reporting in PLOS Pathogens, published by the Public Library of Science, the researchers describe the first genetically engineered approach targeting all four serotypes or strains of the dengue virus, a crucial step for stopping the spread of the disease.
The findings suggest that similar genetic strategies could be developed to control other mosquito-borne arboviruses, including Zika and chikungunya, against which neutralizing antibodies also have been developed, the researchers concluded.
“Transferring the genes for our dengue protective antibody from the human immune system into the genes of mosquitoes, like we did here, opens up many new opportunities to prevent infectious diseases,” said James Crowe Jr., MD, director of the Vanderbilt Vaccine Center, who contributed to the research.
“Stopping dengue virus in the mosquito before it even enters the human body by a mosquito bite may allow us to prevent infection altogether, rather than trying to treat infected humans with illness, when it may be too late to help,” he said.
Dengue fever is a devastating viral disease transmitted by infected Aedes aegypti mosquitoes. It is poorly controlled and is spreading across the globe — 390 million infections are reported each year.
Initially causing severe fever, headache and muscle pain, the infection can progress to life-threatening dengue hemorrhagic fever and dengue shock syndrome. In addition to the human suffering and loss of life, the estimated economic impact of dengue infections tops $40 billion annually.
Six years ago, Crowe and colleagues identified a human monoclonal antibody called 1C19 with “ultrahigh potency” and the capability of neutralizing all four dengue serotypes.
Monoclonal antibodies, like heat-seeking missiles, attack specific viral proteins. Isolated from the blood of people who have survived infections like dengue, they are generated by fusing antibody-producing white blood cell clones to myeloma (cancer) cells to create fast-growing “hybridomas.”
Crowe holds the Ann Scott Carell Chair in the Departments of Pediatrics and Pathology, Microbiology and Immunology. Over the years his lab has isolated human monoclonal antibodies for many pathogenic viruses including Zika, HIV, Ebola, norovirus, respiratory syncytial virus (RSV) and rotavirus.
In the current study, UCSD researchers and colleagues from the National Health Research Institutes in Taiwan and the Commonwealth Scientific and Industrial Research Organization in Australia injected part of the 1C19 antibody gene into mosquito embryos.
Upon reaching adulthood, the genetically engineered mosquitoes expressed a portion of the 1C19 antibody, which rendered them incapable of being infected by or transmitting any of the strains of the dengue virus.
This approach, the researchers predicted, “can provide an effective, sustainable and comprehensive strategy for reducing the impact of arboviral mosquito-borne diseases.”
