|Biologists at the University of California San Diego led the development of the first mosquitoes synthetically designed to halt the transmission of dengue, neutralizing many types of the infectious disease / Photo by: Jarun Ontakrai via 123RF|
Biologists at the University of California San Diego led the development of the first mosquitoes synthetically designed to halt the transmission of dengue, neutralizing many types of the infectious disease. The study, published in the journal PLOS Pathogens, identified a wide range of antibodies in humans to suppress the four known types of dengue virus.
The development is the first engineered technique in mosquitoes that improved on existing approaches that addressed single strains. It comes as the global incidence of dengue grown in recent decades, putting half of the world's population at risk.
A mosquito species known as Aedes aegypti is considered as the primary carrier of the dengue virus (DENV). The Aedes aegypti is found in urban habitats and mostly breeds in man-made containers.
According to the WHO, this species feeds during day time, with peak biting periods in early morning and evening before sunset.
Another dengue-carrying species is the Aedes albopictus, which has spread in the US and Europe due to the international trade in used tires and other goods. This species is highly adaptive; it can tolerate colder conditions, whether as an egg or an adult, allowing it to survive and thrive regardless of its location.
"Aedes albopictus has been implicated as the primary vector of DENV in a limited number of outbreak, where Aedes aegypti is either not present, or present in low numbers," the WHO said.
For the study, the US San Diego biologists—in collaboration with colleagues at Vanderbilt University Medical Center—engineered the Aedes aegypti mosquitoes to impede vector competence to DENV among mosquitoes.
"This is the first engineered approach that targets all DENV serotypes, which is crucial for effective disease suppression," the researchers said in the study. "These results provide a compelling route for developing effective genetic-based DENV control strategies, which could be extended to curtail other arboviruses."
Upon identifying the spectrum of a human antibody to suppress the dengue virus, the researchers designed the "cargo" that allows the antibody to be synthetically expressed in female mosquitoes that spread the dengue virus.
The researchers exposed adult females to a dengue virus—DENV-2—through membrane blood-feeding. Four days later, they found a significant reduction of infection rate from 45 to 71% as well as drops in viral RNA levels.
They replicated the exposure in dengue serotypes DENV-1, DENV-3, and DENV-4 and found that no infection was found in mosquitos exposed to the dengue viruses four days following infection.
"Once the female mosquito takes in blood, the antibody is activated and expressed—that’s the trigger," Omar Akbari, the lead researcher from UC San Diego, explained in a statement. “The antibody [can] hinder the replication of the virus and prevent its dissemination throughout the mosquito, which then prevents its transmission to humans. It’s a powerful approach.”
Akbari added that the engineered mosquitoes could be easily paired with a dissemination system that can spread the antibody among wild disease-transmitting mosquito populations.
"This development means that in the foreseeable future there may be viable genetic approaches to controlling dengue virus in the field, which could limit human suffering and mortality," said the lead author, whose lab is currently testing methods to neutralize mosquitoes against dengue as well as other viruses like Zika, yellow fever, and chikungunya.
The Global Incidence of Dengue
Co-author James Crowe Jr. said the development was "fascinating" and may even lead the path to a new field of biotechnological possibilities that can curb mosquito-borne diseases among humans.
Such developments are important, considering that mosquitoes have been considered as the deadliest insects on the planet for carrying deadly diseases like dengue, malaria, and Zika virus.
The dengue-virus alone threatens half of the world's population as its incidence rates grow dramatically. According to the WHO, estimates show there are 390 million dengue virus infections every year—among which 96 million manifest clinically. The risk of infection exists in 128 countries, but Asia carries a majority of that burden (70%).
Vietnam, Malaysia, the Philippines, and Singapore continue to see increases in dengue cases as they recorded nearly 900,000 cases in 2019—including nearly 2,000 deaths, figures from the WHO shows.
Most of the efforts done to stop the spread of the dengue virus focused on killing the mosquitoes that carry it. It was only recently that the efforts shifted to other methods, such as the work of Akbari's lab.
"Until recently, the world has focused on shooting (killing) this messenger," Suresh Subramani, professor emeritus of molecular biology at UC San Diego and global director of the Tata Institute for Genetics and Society (TIGS), said in a statement.
"Work from the Akbari lab and at TIGS is aimed at disarming the mosquito instead by preventing it from transmitting diseases, without killing the messenger. This paper shows that it is possible to immunize mosquitoes and prevent their ability to transmit dengue virus and potentially other mosquito-borne pathogens."
One of the efforts to controlling dengue is the implementation of thermal fogging, which is employed during outbreaks to curb populations of potentially infectious adult mosquitoes and break the transmission cycles. Researchers studied this method in Colombia to identify the barriers that hinder the implementation of thermal fogging.
They found that that only 53.7% of the 4,455 homes were scheduled for fumigation treatment in response to reports of dengue cases. A small number of households (9.6%) rejected the treatment while the remaining 36.7% were not subject to fumigation due to various reasons (absent residents, no adults being present, etc).
"The most frequent causes for rejection were residents being busy at the time of treatment (33.1%) and no interest in the treatment (24.5%)," the researchers said. "Other reasons for rejection include the perceptions that fumigation does not control pests other than mosquitoes (4.3%), that no mosquitoes were present in the home (3.3%), and that fumigation affects human health (3.1%)."
They concluded that a high percentage of Colombian houses where fumigation was not implemented limited the control of the vector. This finding indicates the need for future strategies to consider more flexible treatment schedules and also implement the distribution of informational messages to educate residents about the safety and importance of treatment.