Could the Mosquito Itself Be the Key to Preventing the Spread of Disease?
Darin Seehafer
Darin Seehafer
Sr. Director, Center for Vaccines and Emerging Infectious Diseases

Though tiny, the mosquito is one of the greatest menaces of all disease-transmitting insects and the cause of more deaths than any other animal on the planet.

What if there were a way to not only limit or prevent mosquito-borne diseases, but also reduce the mosquito population at the very same time? And what if there were a way to make mosquitos themselves the very catalysts?

Want to learn more?

The Discovery Channel will air its special MOSQUITO on July 6 at 9:00 pm EST. The film chronicles the increasing global threat this tiny animal poses and will feature insights from world and health leaders including this potentially ground breaking vaccine technology.

Gregory Stoloff, founder of the London-based pharma company, SEEK, felt sure there must be a more effective approach to tackling the devastating diseases spread by mosquitos. After all, more than a million deaths each year can be attributed to mosquito-transmitted diseases like malaria, dengue, yellow fever, West Nile, Zika, and others.

A Phase I study on this potentially revolutionary vaccine to combat mosquito-transmitted diseases began in February and is sponsored and funded by the National Institute of Allergy and Infectious Diseases (NIAID).

It could be a massive game-changer in the battle against disease.

The Mosquito: Its Own Nemesis

The secret is in the saliva. Typically, a mosquito’s saliva, among other things, invokes a particular immune response that is helpful to the microbes which are carried by that mosquito. This type of immune response allows microbes to hitch a ride in these immune cells, which then travel around the body (undamaged), and then hop out at the site that is most favorable for their multiplication.

The mosquito saliva vaccine – called AGS-v – is designed to create an anti-saliva immune response in humans that prevents infection from the microbes carried by the mosquito, by altering the type of immune response so the microbes can’t travel undamaged around the body.

According to Stoloff, the mechanism aims to change the human response to saliva from Th2 to Th1 (see image). An added benefit is that after the mosquito feeds on a vaccinated human, antibodies in the blood should attack the salivary proteins in the mosquito, which would impact its ability to feed and lay eggs — leading to its death.

Mosquito vaccine

Once the immune system is changed from a Th2 to a Th1 environment, Stoloff says, it will remain this way. Then, every time you are bitten by a mosquito, your immune system will act in a Th1 manner. The microbes won’t be able to jump in cells and travel around the body undamaged. This means less or no disease from these microbes.

Using natural saliva was not an option for the researchers, since the amount of vaccines available from this approach would be limited. Stoloff and his team developed synthetic saliva to overcome this issue.

If successful, the AGS-v vaccine could revolutionize the fight against mosquito-borne diseases and significantly impact the public health and economies of vulnerable populations. Using one vaccine to combat multiple diseases also offers huge economic advantages.

According to a recent draft of the WHO’s Global Vector Control Response, “Vector-borne diseases exact an immense toll on economies and restrict both rural and urban development.” Further, “Reductions in vector-borne diseases will enable greater productivity and growth, reduce household poverty, increase equity and women’s empowerment, and strengthen health systems…”

Despite widespread efforts to vaccinate and protect against this killer, mosquito vector diseases (and populations) remain endemic in much of the world. Now with new concerns related to warming trends across the globe, mosquitos could carry life-threatening diseases into new territory.

AGS-v Clinical Trial

The Phase I double-blind clinical trial will enroll up to 60 healthy adults ages 18 to 50. Each participant will be randomly assigned to receive one of three vaccine regiments. The first group will receive two injections of AGS-v, the second group two vaccine injections combined with an adjuvant (oil and water), and the third group will receive two placebo injections of sterile water. Each group’s injections will be administered 21 days apart.

After those three weeks, participants will undergo a 20-minute controlled exposure to the bites of mosquitos carrying no viruses or parasites. Later, study investigators will take blood samples from participants to measure the levels of antibodies triggered by vaccination. The mosquitos themselves will also be studied for changes to their life cycle; having ingested blood containing ASG-v, they may die early or have trouble reproducing. If so, the vaccine should help reduce the mosquito population.

Study investigators hope to complete enrollment by August 2017. All human participants will return for follow-up visits every 60 days for five months after the mosquito feeding. A final visit 10 months later will assess long-term safety. Initial results could be available by early fall 2017, with the entire study results expected by summer 2018.

What’s Next?

Once completed, the Phase I trial should determine if the vaccine is safe and can generate the desired immune response. In this case, they hope to apply to the U.S. FDA for Fast Track or breakthrough designation and perhaps skip Phase II trials and go straight to Phase III.

Stoloff feels there is such a great need for a universal mosquito vaccine like this that it is possible AGS-v would be granted such an exception based on a successful and compelling Phase I trial.

If successful this vaccine would be low cost and economical for low income countries. Stoloff and team hope to be able to work with the WHO and Bill & Melinda Gates Foundation and other such parties to distribute this vaccine and to mobilize these low income countries to vaccinate their citizens. This vaccine could also be used for travelers to infected regions and to reduce allergies to mosquito saliva bites.

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