With mosquito-borne illnesses posing an ongoing public health threat around the world, there is a significant need for advances in combating and controlling mosquito vectors. Although outbreaks of Zika virus have brought this particular disease to the forefront in recent years, it is only one of several mosquito-borne illnesses that infect and kill people each year.
“We’re aware of Zika because it is new on the public health radar and it’s a significant issue, but the burden of disease and the amount of illness caused by diseases like dengue and chikungunya in areas around the world is considerable every single year,” Matt Zahn, MD, chair of the Infectious Diseases Society of America’s Public Health Committee, told Infectious Disease News. “Having a vaccine that would protect against these diseases and generally against a vector that is one of the larger spreaders of serious viral infections would be a huge advance.”
Although such an advance is not yet on the immediate horizon, the possibility is now being investigated. The NIH’s National Institute of Allergy and Infectious Diseases (NIAID) has initiated a phase 1 clinical trial of an investigational vaccine designed to confer broad protection against a range of mosquito-borne diseases, including Zika, malaria, West Nile fever and dengue fever, according to a press release. Additionally, the investigational vaccine, called AGS-v, which was developed by the London-based pharmaceutical company SEEK, is intended to inhibit the ability of mosquitoes to transmit these infections. The vaccine is distinct from other vaccines, which target specific mosquito-borne illnesses, in that it is designed to prompt an immune response to mosquito saliva rather than to a specific virus or parasite carried by mosquito vectors.
“This is very early — it’s a first-time, phase 1, first-in-human trial,” said lead investigator Matthew J. Memoli, MD, director of the Clinical Studies Unit at the NIAID’s Laboratory of Infectious Diseases. “We can’t expect everything all at once, but I think if we have good results from this study, it’s going to open the door for more work to be done in this area, which is going to help us answer some important questions and potentially lead to improved development of vaccines to prevent these diseases.”
A unique mechanism
According to Memoli, the AGS-v was developed based on an understanding of the various and complex proteins contained in mosquito saliva.
“We’re finding that mosquito saliva contains a lot of proteins — over 100 proteins in different mosquito saliva,” Memoli said. “These proteins have many different functions, related mainly to improving the ability of the insect to feed on the host. They have, for instance, anticoagulants that thin the blood, vasodilators to help bring blood to the site, and even certain kinds of proteins that perform immunomodulatory functions, things to prevent the immune system from interfering with feeding.”
Memoli said arboviruses like West Nile, Zika and dengue, as well as parasites like malaria, appear to evolve over time to take advantage of these functions.
“Some of the functions that these proteins have to modulate the immune system basically set up an environment in the skin that makes it easier for the organisms to cause an infection,” he said.
The AGS-v vaccine is designed to induce a change in the typical immune response to a mosquito bite by sensitizing the body to the peptides in the vaccine, Memoli said.
“Typically, you have an allergic response to a mosquito bite, and that allergic response actually suppresses some of the antiviral and antiparasitic responses so that those organisms can then infect macrophages and dendritic cells, and be brought into the bloodstream and out to the peripheral tissues,” he said. “The idea behind this vaccine is that because someone who gets the vaccine is sensitized to the peptides in the vaccine, they now have more of a Th1–associated response when they get bitten by a mosquito. This allows activation of macrophages, activation of dendritic cells, and production of interferons that prevent the organisms from infecting those cells and moving into the bloodstream.”
The vaccine would essentially interrupt this process and induce more of an “anti-organism response,” Memoli said.
“Of course, the benefit to this is that if it works with one vaccine, you could potentially interfere with a huge number of infections,” he said.
Zahn agreed that if the vaccine is successful, it would likely play a significant role in public health.
“It’s a very intriguing notion,” he said. “The possibility of one vaccine providing protection against multiple or all of these pathogens is very exciting from a public health standpoint.”
A realistic prospect?
According to Memoli, it is too soon to know whether the AGS-v vaccine will achieve its goal of reducing mosquito-borne infection. He said that although the connection between mosquito saliva and infection is now known, the study will seek to determine whether disrupting this process will have a significant impact on reducing infection.
“What we’re trying to find out with this study is, number one, is a mosquito saliva vaccine safe in humans — can we actually do this?” he said. “Two, if it’s safe, can we induce a response with a mosquito saliva vaccine? And if we then can induce a response, will that response actually have an impact on preventing infection?”
Memoli expects the study to answer the first and second questions, but the third will likely be answered in a later phase study.
According to Zahn, it will likely be years before such a vaccine would become available, provided that the clinical trials are successful. However, the fact that the NIH placed its confidence in the study is encouraging, he noted.
“I would say that once the NIH is sponsoring a phase 1 trial, that means there’s some comfort level here that the science makes sense,” he said. “We certainly know that the mosquito’s saliva pays an integral role in allowing for infection to take place, and there are specific parts of that saliva that facilitate infection. Inhibiting that process, which is really what this vaccine proposes to do, makes sense from a physiologic standpoint.”
Memoli agreed that it is too soon to speculate on how long it will take for the vaccine to become available to the public, but he acknowledged the important implications of this innovation if it were to come to fruition.
“If something like this were to work, whether this vaccine or a future vaccine using a similar technology, it would really be hugely important,” he said. “To be honest, it would probably be a game-changer in vector-borne infection, especially since the majority of people who are affected by vector-borne diseases live in developing countries with less access to health care. Being able to combine multiple diseases into a single vaccine would be a huge time-saving, money saving and probably lifesaving thing.”
Source: Healio
