(Reuters) – Five years ago, in an office complex with a giant sculpture of a mosquito just northwest of Phnom Penh, Jessica Manning came up with a new idea. Instead of spending more years in what felt like a pointless search for a malaria vaccine, she would take on all mosquito-borne pathogens at once.
Her idea revolved around mosquito spit.
Based on work with colleagues and other researchers, Manning, a clinical researcher for the U.S. National Institute of Allergy and Infectious Diseases, that she could use bits of mosquito repellent protein to build a universal vaccine.
The vaccine would, if it pans out, protect against all pathogens that the insects inject into humans ̵
“We need more innovative tools,” Manning said. A vaccine like this would be “the holy grail.”
On Thursday, The Lancet published the first results of this work with their colleagues: the first clinical trial of a mosquito bite vaccine in humans.
The study showed that a mosquito-based vaccine from Anopheles was safe and that it triggered antibodies and cellular responses.
Michael McCracken, a researcher not involved in the study, called the original results “basic.”
“This is a big, important job,” said McCracken, who studies the immune response to mosquito-borne viruses at the Walter Reed Army Institute of Research in Maryland. “Mosquitoes are arguably the deadliest animal on earth.”
Malaria kills just over 400,000 people each year, according to the World Health Organization. These deaths occur most often in poor countries that do not receive as much vaccine research and funding. However, due to global warming, the mosquitoes that thrive in the tropics are moving to more countries each year.
The global disruption of the COVID-19 pandemic has given a strong focus on infectious diseases and vaccine research. One of the most important areas of concern is pathogens transmitted by mosquitoes.
The new coronavirus, which is believed to originate in bats, has so far infected more than 7.4 million people and killed nearly 420,000 worldwide. The Asian Development Bank estimates that the pandemic could cost the global economy as much as $ 8.8 trillion.
Mansing’s research is specific to mosquitoes, but is an example of how researchers are broadening their minds on how to manage infectious diseases and the new types of tools they are developing.
What Manning is looking for is a vector-based vaccine. A vector is the living organism – like a mosquito – that transmits a pathogen such as malaria – between humans, or from animals to humans.
All existing vaccines for humans target a pathogen. Mansing goes after the vector.
The idea is to train the body’s immune system to recognize the saliva proteins and get an answer that would weaken or prevent an infection.
Researchers have known for decades that mosquito bites help to establish mosquito-borne infections and increase their severity. Recently, researchers have begun to exploit this.
A study of macaque monkeys published in 2015 showed that vaccination with sand fly saliva reduced leishmaniasis lesion size and parasite load. A study of mice published in 2018 showed immunization with Anophele’s mosquito bite protected against malaria. Another mouse study published last year showed that immunization with Aedes mosquito larvae improved survival against the Zika virus.
The study published in The Lancet was conducted in 2017.
The Phase I trial conducted at the National Institutes of Health Clinical Center in Bethesda, Maryland, was tested for the safety and side effects of 49 healthy volunteers.
Participants were randomly assigned to receive one of two versions of the vaccine or a placebo. After a few weeks, hungry mosquitoes were placed on the participants’ arms. The study measured immune response to mosquito injection proteins but did not involve pathogens.
More studies are needed to determine the effect that the mosquito saliva vaccine would have on actual pathogens.
No systemic security problems were identified. One participant developed an 8 cm (3.15 inch) red area around the injection site and was treated with steroids and antihistamines.
“I’m not as worried about redness as I would be about something more systemic like fever, headache, muscle pain, nausea or vomiting,” said Stephen Thomas, an infectious disease expert at SUNY Upstate Medical University who was not involved in the study.
Thomas has previously worked with dengue vaccine programs for the US Department of Defense and helped manage his response to Ebola and the Zika virus.
Another researcher at the University of Maryland is conducting a follow-up study with more mosquito proteins and another vaccine formulation.
Meanwhile, Manning has returned to Cambodia and is conducting a field study to identify vaccine candidate mock proteins in Aedes mosquitoes. She also has a separate project that sequences the genomes of all pathogens found in Aedes and Culex mosquitoes, some of which can infect humans.
An alarming discovery so far? “They have lots of different viruses that we only detect.”
Reporting by Clare Baldwin; Editing by Elyse Tanouye and Bill Berkrot