Testing a Novel Vaccine Against Mosquito-Borne Diseases

In an interview with Contagion®, Matthew J. Memoli, MD, MS, director of the Laboratory of Infectious Disease Clinical Studies Unit, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland acknowledged the numerous vector-borne diseases that affect millions of individuals around the world.

These diseases are carried by mosquitoes and other insects and are a significant problem in the developing world. “Now, some of these diseases have even spread into the western world and are causing problems in the industrial world,” he added.

With this in mind, Dr. Memoli is leading a phase 1 trial to evaluate an investigational vaccine, known as AGS-v, which is designed to provide broad protection against a range of mosquito-transmitted diseases. Dr. Memoli noted that the study will examine a new approach to protecting individuals from vector-borne disease, by using mosquito saliva. Whereas other vaccines for these types of diseases typically target a specific infectious organism carried by mosquitoes, this new vaccine contains four synthetic peptides from mosquito salivary glands, and is designed to trigger an immune response to mosquito saliva, he emphasized.

Therefore, by targeting mosquito saliva, this type of vaccine could potentially protect against multiple diseases at the same time, Dr. Memoli emphasized. “This could be extraordinarily useful, especially when dealing with trying to deploy vaccines to the developing world where money is tight and it’s difficult to deliver many vaccines.”

Although the peptide antigens in the HIV vaccine and influenza vaccine are different from those in the mosquito-borne disease vaccine, the same technology was used to develop all three vaccines. Dr. Memoli stressed that both the HIV vaccine and influenza vaccine have been shown to be quite safe; both have advanced through phase 1 trials and are now in phase 2 trials, and have had very few associated adverse events. This highlights the safety of the technology used to develop the investigational mosquito-borne diseases vaccine, he explained. The new investigational vaccine has also been evaluated in animal studies, with no concerning safety signals seen.

The trial is a double-blind study which will randomize participants into three groups, to receive injections of either vaccine, vaccine plus adjuvant, or placebo (sterile water). Dr. Memoli anticipates that the study will recruit a maximum of 60 healthy participants, ranging in age from about 18 to 50 years.

Although an important primary goal of the study is to check the safety of the vaccine in humans, Dr. Memoli added that it also aims to provide insight into the ability of the vaccine to induce the type of immune response that he hopes will be protective when the vaccine is delivered in the field to individuals at risk of disease.

Study participants will receive two injections, 21 days apart. Another 21 days after receiving the second injection, they will experience a “clean mosquito feeding.” Dr. Memoli explained that this involves exposing the participants to biting mosquitoes that have been bred in controlled conditions and have undergone testing to prove they are free of diseases. Approximately five to 10 mosquitoes contained in a special feeding device will be placed on the participants’ arms and will be allowed to feed.

The researchers will collect blood samples from the participants after each injection, as well as after the mosquito feeding, and will follow participants for up to one year. They will evaluate blood samples to assess the safety of the vaccine and the immune response in the participants, said Dr. Memoli. “We will look at antibodies that have been produced in the blood, and will take the polymorphonuclear leukocytes from the blood to test in the lab to see how these white blood cells respond to both mosquito saliva and certain viruses coded with mosquito saliva.”

He explained that this will determine whether the vaccine induces the anticipated modified immune response against mosquito saliva that will prevent infection of individuals who are bitten by disease-carrying mosquitoes. “This change in response is what we hope will protect individuals in the future when we deliver this in a phase 2 trial,” he stressed.

Although Dr. Memoli recognizes that this is the first time such an approach targeting mosquito saliva is being tested in humans, he believes the study has the potential to provide a lot of useful data, and hopes it “leads to an improved ability for the entire scientific community to further develop good counter measures for these vector-borne diseases.”

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.