How a vaccine made of mosquito spit could help stop the next epidemic

By Clare Baldwin

(Reuters) – Five years ago, in an office complex with a giant sculpture of a mosquito just northwest of Phnom Penh, Jessica Manning struck on a novel idea. Rather than spend more years in what felt like a futile search for a malaria vaccine, she would take on all mosquito-borne pathogens at once.

Her idea revolved around mosquito spit.

A lab technician Nhek Sreynik works with mosquitoes, at a lab in Kompong Speu Province, in Cambodia, June 11, 2020. REUTERS/Chantha Lach

Building on the work of colleagues and other scientists, Manning, a clinical researcher for the U.S. National Institute of Allergy and Infectious Diseases, believed she could use pieces of mosquito saliva protein to build a universal vaccine.

The vaccine, if it pans out, would protect against all of the pathogens the insects inject into humans – malaria, dengue, chikungunya, Zika, yellow fever, West Nile, Mayaro viruses and anything else that may emerge.

“We need more innovative tools,” said Manning. A vaccine like this would be “the Holy Grail.”

On Thursday, The Lancet published the initial results of this work with her colleagues: the first-ever clinical trial of a mosquito spit vaccine in humans.

The trial showed that an Anopheles mosquito-based vaccine was safe and that it triggered antibody and cellular responses.

Michael McCracken, a researcher not involved in the study, called the initial results “foundational.”

“This is big, important work,” said McCracken, who studies immune responses to mosquito-borne viruses at the Walter Reed Army Institute of Research in Maryland. “Mosquitoes are arguably the deadliest animal on Earth.”

A boy sits in the pediatrics ward at Kampong Speu District Referral Hospital, at the beginning of a dengue, also called ‘breakbone fever’, epidemic in Krong Chbar Mon, Cambodia April 2019. Jessica Manning/Handout

Malaria alone kills more than 400,000 people each year, according to the World Health Organization. Those deaths occur mostly in poor countries that do not receive as much vaccine research and funding. Because of global warming, however, those mosquitoes that thrive in the tropics are moving into more countries each year.

The global disruption of the COVID-19 pandemic has brought a sharp focus to infectious diseases and vaccine research. One of the key areas of concern are pathogens transmitted by mosquitoes.

The novel coronavirus, believed to have originated in bats, has so far infected more than 7.4 million people and killed nearly 420,000 worldwide. The Asian Development Bank estimates the pandemic could cost the global economy as much as $8.8 trillion.

TARGETING THE CARRIER

Manning’s research is specific to mosquitoes but is an example of how scientists are broadening their thinking about how to tackle infectious diseases, and the new types of tools they are developing.

What Manning is looking for is called 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. Manning’s goes after the vector.

The idea is to train the body’s immune system to recognize the saliva proteins and mount a response that would weaken or prevent an infection.

Scientists have known for decades that mosquito spit helps establish mosquito-borne infections and enhance their severity. Just recently, scientists have begun to exploit this.

A study of macaque monkeys published in 2015 showed vaccination with sand fly saliva reduced leishmaniasis lesion size and parasite load. A study of mice published in 2018 showed immunization with Anopheles mosquito spit protected against malaria. Another mouse study published last year showed immunization with Aedes mosquito saliva 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, tested for safety and side effects in 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 arms of study participants. The study measured immune response to the mosquito spit proteins but did not involve pathogens.

More trials are needed to determine the effect the mosquito spit vaccine would have against actual pathogens.

No systemic safety concerns were identified. One participant developed an 8-centimeter (3.15 inches) reddened 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 aches, nausea or vomiting,” said Stephen Thomas, an infectious disease expert at SUNY Upstate Medical University who was not involved with the study.

Thomas has previously worked on dengue vaccine programs for the U.S. Department of Defense and helped manage its response to Ebola and the Zika virus.

Another scientist at the University of Maryland is running a follow-up trial with more mosquito spit proteins and a different vaccine formulation.

Meanwhile, Manning has returned to Cambodia and is running a field study to identify vaccine-candidate spit proteins in Aedes mosquitoes. She also has a separate project sequencing the genomes of all pathogens found in Aedes and Culex mosquitoes, some of which can infect humans.

One worrying discovery so far? “They carry a ton of different viruses that we are only just discovering.”

(Reporting by Clare Baldwin; Editing by Elyse Tanouye and Bill Berkrot)

Exclusive: U.S. needs to improve oversight of labs handling dangerous pathogens – report

Exclusive: U.S. needs to improve oversight of labs handling dangerous pathogens - report

By Julie Steenhuysen

CHICAGO (Reuters) – A year-long audit of the program overseeing U.S. labs that handle lethal pathogens such as Ebola and anthrax found overworked safety inspectors, an absence of independent review and weak biosafety protections that could expose lab workers and the public to harm, a government report will say on Tuesday.

The report by the Government Accountability Office to Congress followed a series of mishaps in which dangerous pathogens were inadvertently released. The report, seen by Reuters, concluded that the Federal Select Agent Program needs an overhaul.

The GAO audited laboratory safety oversight following errors that could have exposed dozens of people to live anthrax bacteria and the deadly toxin ricin. Its report will guide questioning of officials before the House Energy and Commerce Committee’s oversight subcommittee on Thursday.

The Federal Select Agent Program is jointly run by the U.S. Centers for Disease Control and Prevention (CDC) and the Animal and Plant Health Inspection Service (APHIS) of the U.S. Department of Agriculture.

According to the report, a chief concern is that the program is too focused on physical security measures, such as preventing theft from labs, and needs to focus more on biosafety issues that could protect researchers and the wider public from errors.

The GAO report also noted that many of the labs using high-risk pathogens for research belong to either CDC or the USDA, and recommended that Congress consider setting up a fully independent oversight body to remove potential conflicts of interest.

“The Select Agent Program does not fully meet our key elements of effective oversight,” the report stated.

Safety lapses in CDC labs captured headlines in 2014 when scientists at a high-level biosecurity lab did not properly inactivate anthrax bacteria before sending the material to labs with fewer safeguards. More than 80 scientists were exposed to potentially live anthrax, though no one fell ill.

In the months that followed, the Food and Drug Administration disclosed the discovery of decades-old vials of smallpox in a storage closet, while a U.S. Army lab erroneously shipped live anthrax to nearly 200 labs worldwide.

To address concerns of conflict of interest, CDC and APHIS have made structural changes to increase the program’s independence, but according to the GAO report, the program has not undergone a comprehensive risk management review, even as problems with lab safety continue to come to light.

As recently as last November, the Department of Homeland Security found a private lab inadvertently shipped ricin – a lethal poison – to one of its training centers on multiple occasions in 2011.

“Considering the type of research we’re talking about, we should have a much more robust, systematic oversight approach. That seems to be lacking,” said an aide to the House committee who declined to be identified.

To avoid conflicts of interest, inspections of APHIS laboratories are supposed to be carried out by the CDC, and inspections of CDC labs are to be carried out by APHIS. But the report revealed that at least three times in 2015, APHIS inspected its own laboratories, partly because there is no process in place to ensure compliance.

The report also cited excessive workloads for inspectors, which delay inspection reports and make it harder to retain personnel. In some cases, inspectors have been assigned to tasks outside of their expertise. For example, the GAO found that an APHIS physical security expert was asked to inspect ventilation systems – a critical protection against the accidental release of dangerous pathogens.

Short of a move by Congress to create an independent oversight agency, GAO recommended that CDC and APHIS officials conduct a risk assessment of the Select Agent Program and how it handles conflicts of interest. It also recommended that program officials shift inspection priorities to focus on high-risk activities in labs and develop a joint plan to train and hire inspectors.

The Health and Human Services Department, which oversees CDC, and the USDA, which runs APHIS, agreed with many of these recommendations, according to the report. Officials from the CDC and APHIS will testify at the Thursday hearing.

(Reporting by Julie Steenhuysen; Editing by Michele Gershberg)