Mosquito-Delivered Vaccines: The Future of Zoonotic Disease Control?
Researchers Discover a New Strategy to Slow Zika Virus Spread
Zika virus is endemic in many tropical regions, including Central and South America and Africa. It is spread to humans by infected mosquitoes, which pick the virus up from human or primate reservoirs. Humans infected with Zika are often asymptomatic or have a mild fever and muscle aches.
However, Zika infections in pregnant patients are a major concern. Pregnant women infected with Zika have an elevated risk of miscarriage, and their baby may have birth defects such as microcephaly (abnormally small head and brain). It is important to note that these negative outcomes do not always occur, and Zika infections do not affect future pregnancies.
There are presently no vaccines or treatments for Zika infection, but it has been theorized that the spread of Zika from wild populations to human populations could slowed down by vaccinating wild hosts. Capturing and vaccinating individual wild monkeys is impractical, but an easier method has recently been proposed. Over the past few years, a group of researchers have investigated the safety and efficacy of vaccinating animals against Zika using a mosquito-delivered vaccine.
The first challenge this group faced was designing a vaccine for Zika that could be safely used in wild populations. The concept behind a vaccine is acquired immunity. Vaccines introduce a dead or weakened version of a pathogen into the body to teach the immune system to recognize features of that pathogen (such as its membrane proteins). Later, when the vaccinated organism is exposed to the actual pathogen, its immune system will rapidly recognize those features and destroy the pathogen.
The researchers knew that a different virus, Chaoyang virus, thrives in mosquitoes but does not replicate well in vertebrate cells. They engineered a new version of Chaoyang virus that had envelope and membrane proteins from Zika virus. This is known as a chimeric vaccine because it combines components from multiple viruses (in Greek mythology, a chimera is a creature that blends the physical features of a lion, a goat, and a snake). As expected, the new virus (named CYV-ZIKV) could replicate in mosquitoes, but not in vertebrates.
When the researchers fed Aedes aegypti mosquitoes with blood containing CYV-ZIKV, the infected mosquitoes were unharmed and could transmit it to the organisms they bit. Additionally, the virus’ unusual structure rendered it impossible for the mosquitoes to transmit it to their mates or offspring. This was an important finding because it meant that the engineered virus had a low potential for spread in wild mosquito populations. Due to safety concerns, the researchers took the additional precaution of rendering the mosquitoes infertile by exposing them to X-rays. This did not affect the ability of the mosquitoes to carry the virus in their saliva and ensured that the virus could not possibly be transmitted to their offspring.
The researchers also experimentally evaluated the susceptibility of the engineered virus to mutation and found that it was unlikely to gain the ability to reproduce in vertebrates. This was important because it indicated that the virus was not likely to evolve pathogenic capabilities.
Once these initial safety concerns had been evaluated, the researchers tested the vaccine on animals. Mice were exposed to CYV-ZIKV via infected mosquito bites, and no replication of the engineered virus was detected at the sites of exposure. This aligned with the researchers’ expectations. When the mice were subsequently exposed to Zika virus, they demonstrated immunity to Zika and were unable to transmit Zika to mosquitoes. The exposure to CYV-ZIKV was therefore sufficient to cause antibody production against Zika. However, mice exposed to the engineered virus on multiple occasions exhibited much higher antibody levels than mice that were bitten only once.
This study showed that it is theoretically possible to reduce the spread of a zoonotic virus by using a mosquito to deliver a modified, harmless version of the virus. If properly regulated, herd immunity could develop within the virus’ wild reservoir, reducing the potential for spillover into human populations and improving the survival of endangered species. Eventually, this technique may be tested in the wild. However, there are many safety concerns that must be studied to ensure that this method does not bring about unintended consequences.
If properly regulated, herd immunity could develop within the virus’ wild reservoir, reducing the potential for spillover into human populations and improving the survival of endangered species.
If this technique becomes commonplace, it will require continual human supervision. Since the engineered virus cannot be spread within mosquito populations and does not replicate in vertebrate cells, it will be necessary to artificially produce the virus, treat batches of mosquitoes with X-rays to ensure their inability to reproduce, infect the mosquitoes with the virus, and introduce them into the environment. Release of mosquitoes will have to be strategically timed to ensure that primates receive an optimal number of booster doses of the vaccine. Lastly, careful environmental monitoring will be necessary to ensure that the vaccine does not evolve harmful features or produce unforeseen consequences.
