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.


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)

Miami among cities at risk from yellow fever spread : study

FILE PHOTO: The downtown skyline of Miami, Florida is seen on Nov 5, 2015. REUTERS/Joe Skipper/File Photo

GENEVA (Reuters) – Miami is at risk of a deadly yellow fever outbreak because the disease could thrive there but the city has no checks on travelers arriving from endemic zones, a study to be published by the World Health Organization showed.

Yellow fever is spread by the same mosquito that causes Zika virus, which spread through the Americas after being detected in Brazil in 2015 and has been reported in southern Florida and southern Texas.

The U.S. Centres for Disease Control advises that yellow fever is found in tropical and subtropical areas of Africa and South America, and is a very rare cause of illness in U.S. travelers.

But the study, “International travel and the urban spread of yellow fever”, showed that almost 2.8 million people flew to the United States from endemic yellow fever areas in 2016.

Unlike some countries, the United States does not require travelers from such places to show proof of yellow fever vaccination.

“At a time when global yellow fever vaccine supplies are diminished, an epidemic in a densely populated city could have substantial health and economic consequences,” the researchers based in Canada, the United States and Britain wrote in the study.

Around 9.5 million people live in U.S. urban areas such as Miami that are ecologically suitable for an outbreak, they wrote in the study, issued online ahead of its publication in the Bulletin of the World Health Organization.

They said climate change, mobility, urbanization and a vaccine shortage had increased the risk of yellow fever globally and they called for a review of vaccination policies.

The study found 472 cities suitable for an outbreak in 54 countries, but many, such as New Delhi, Mumbai, Karachi, Manila and Guangzhou, required vaccination certificates on arrival from endemic countries.

WHO spokeswoman Fadela Chaib said the need for vaccination certificates was at each country’s discretion.

The researchers said a substantial proportion of the world’s yellow fever vaccine stocks had been used up by recent epidemics in Africa and Brazil, and further depleted by manufacturing difficulties. Preventive campaigns could cause shortages.

“Should another urban epidemic occur in the near future, vaccine demand could easily exceed the available supply,” they said.

Yellow fever, which can be hard to diagnose, causes symptoms including muscle pain, nausea and vomiting, and about 15 percent of cases lead to a more toxic phase within 24 hours, potentially experiencing jaundice, abdominal pain, deteriorating kidney function and bleeding from the mouth, nose, eyes or stomach.

Half of severe sufferers die within a week or two, but the rest recover without significant organ damage, according to WHO.

(Reporting by Tom Miles; Editing by Hugh Lawson)

Yellow fever kills 600 monkeys in Brazil’s Atlantic rainforest

woman works on yellow fever vaccine

By Anthony Boadle

BRASILIA (Reuters) – An outbreak of yellow fever has claimed the lives of more than 600 monkeys and dozens of humans in Brazil’s Atlantic rainforest region, threatening the survival of rare South American primates, a zoologist said on Wednesday.

The monkeys, mostly brown howlers and masked titis, are falling out of trees and dying on the ground in the forests of Espirito Santo state in Brazil’s southeast.

“The number of dead monkeys increases every day,” said Sergio Lucena, he said of the impact of the disease’s spread in his state, “We now know that the rare buffy-headed marmoset is also threatened by the yellow fever virus and dying.”

The howler’s sounds closely resemble grunts or barks. It was the silence that fell on the forests that first alerted farmers that something was amiss, sparking specialists to investigate.

The masked titi is considered as “vulnerable” by the Swiss-based International Union for Conservation of Nature, which has placed it on its Red List of Threatened Species.

No evidence has so far surfaced of the affliction felling woolly spider monkeys, considered one of the world’s most endangered by the IUCN.


Brazil is suffering the worst yellow fever outbreak in decades that has killed at least 69 humans, nearly all in central state of Minas Gerais, where the problems began.

Most people recover from yellow fever after the first phase of infection, which usually involves fever, headache, shivers, loss of appetite and nausea or vomiting, according to the World Health Organization.

Millions of Brazilians have been vaccinated as health authorities scramble to prevent the outbreak from turning into an epidemic. There is no such protection available for monkeys.

Yellow fever is a viral disease found in tropical regions of Africa and the Americas that mainly affects humans and monkeys and is transmitted by the same type of mosquito that spreads dengue and the Zika virus.

Hundreds of thousands of people died from it in the Americas before a vaccine was developed in 1938.

Brazil’s federal health officials are investigating if the latest outbreak is linked to a tailings dam collapse last year in Minas Gerais at the Samarco iron ore mine co-owned by BHP
Billiton and Vale SA.

The dam accident, which polluted the Rio Doce river, is regarded as the country’s worst environmental disaster.

Some scientists have said that calamity may have made the monkeys more susceptible to contracting yellow fever by decimating their habitat and food supplies.

Congo almost runs out of yellow fever vaccine amid epidemic

Residents read newspapers with reports on Yellow Fever

By Aaron Ross

KINSHASA (Reuters) – Democratic Republic of Congo has almost run out of yellow fever vaccine in Kinshasa, in the same week that the government declared an epidemic of the disease in the packed capital and two other provinces.

Some local people have complained they were denied immunization due to the shortage, despite queueing for a shot. More supplies have been promised, but health officials in the impoverished country say they have to choose between the high cost of flying them in, or a long wait for shipment by sea.

The mosquito-borne hemorrhagic virus is a major concern in Kinshasa, a city of about 12 million people which has poor health services, a humid climate beloved of the insects and much stagnant water where they can breed owing to pour drainage.

Health minister Felix Kabange said on Monday that 67 cases had been confirmed in Kinshasa, Kongo Central and Kwango provinces and that over 1,000 more suspected cases are being monitored. Five people have died from the disease.

The government and international health organizations vaccinated more than 2 million people, about half of them in Kinshasa, between May 26 and June 4.

But there is no more vaccine left, aside from a small number of doses left in reserve in Kongo Central and some being administered by a government agency at Kinshasa’s central hospital, airport and river crossing with neighboring Congo Republic, health officials said.

The agency is charging $35 for the doses it administers, a hefty sum in a country whose gross national income per person is estimated by the World Bank at $380 a year.

Eugene Kabambi, the World Health Organization (WHO) spokesman in Congo, said that the International Coordinating Group on vaccine provision has promised Congo more than a million more doses.

“That requires either a cargo flight, in which case it would come very quickly but cost a lot, or if it’s by boat, it could take a few weeks,” he told Reuters.

The Coordinating Group brings together the WHO and United Nations Children’s Fund (UNICEF) with the International Federation of Red Cross and Red Crescent Societies plus the medical charity Médecins sans Frontières.

The global stockpile of yellow fever vaccine has already been depleted twice this year to immunize people in Angola, Uganda and Congo. It stands at 6 million doses, but this may not be enough if there are simultaneous outbreaks in a number of highly-populated areas, experts warn.

Almost 18 million doses have been distributed for emergency vaccination campaigns so far in the three African countries.


Congo has extensive experience of dealing with outbreaks of tropical diseases and the Ebola virus was first identified in the central African country.

It earned plaudits in 2014 for quickly containing a local Ebola outbreak that killed 49 people in the country. By contrast an Ebola epidemic killed more than 11,300 as it swept through West Africa from 2013.

Of the cases confirmed in the latest yellow fever outbreak, seven were locally transmitted in Congo. Another 58 were imported from Angola, where it began, and two came from remote forested areas not linked to the current outbreak.

Symptoms of the disease include fever, body aches and nausea, although most people recover.

In Kinshasa’s Ndjili commune, a maze of narrow alleys and one of the health zones in the city targeted for vaccination in late May, many residents were unable to receive an injection before stocks ran out.

“Everyone started coming, even from other districts. Near the end we realized that the vaccine was insufficient,” said Murphy Nzuzi, a doctor at a dimly-lit health center in Ndjili with only a few small treatment rooms. He added that fights had broken out among people waiting in line.

In a nearby market where trash collected in a small stream, residents said that some people had received vaccination papers while waiting in line but never got a shot.

“When you present yourself, they give you the card that gives you access to the vaccine, but then there wasn’t enough vaccine for everyone,” said local resident Mama Mavungu.

The current method for making vaccines, using chicken eggs, takes a year. Health authorities are considering using a fifth of the standard dose of vaccine – enough to immunize temporarily but not to give lifelong immunity – to maximize its availability, but no final decision has been made.

(Editing by Tim Cocks and David Stamp)

Congo declares yellow fever epidemic, 1,000 suspected cases

residents reading reports of yellow fever

KINSHASA (Reuters) – Democratic Republic of Congo on Monday declared a yellow fever epidemic in three provinces, including the capital Kinshasa, after confirming 67 cases of the disease, with another 1,000 suspected cases being monitored.

Health Minister Felix Kabange said only seven of the proven cases were indigenous to the Central African country, while 58 were imported from Angola, where the outbreak began. A further two cases came from remote forested areas not linked to the current outbreak. Five people in total have died, Kabange added.

“I declare today a localized epidemic of yellow fever in the provinces of Kinshasa, Kongo Central and Kwango,” Kabange told a news conference.

Kinshasa is the primary concern for global health officials since it has a densely-packed population of more than 12 million and poor healthcare infrastructure.

Yellow fever is transmitted by the same mosquitoes that spread the Zika and dengue viruses, although it is a much more serious disease. The “yellow” in the name refers to the jaundice that affects some infected patients.

The global stockpile of vaccines has already been depleted twice this year to immunize people in Angola, Uganda and Congo. It stands at 6 million doses, but this may not be enough if there are simultaneous outbreaks in multiple highly-populated areas, experts warn.

Almost 18 million doses have been distributed for emergency vaccination campaigns so far in the three African countries.

The current method for making vaccines, using chicken eggs, takes a year.

World Health Organisation (WHO) advisers have recommended using a fifth of the standard dose of vaccine in the event of a global shortage – enough to immunize temporarily but not to give lifelong immunity.

“An epidemic in such a large city (as Kinshasa) is always difficult to handle,” said WHO’s Congo representative Yokouide Allarangar.

A vaccination campaign has been staged in two of the city’s health zones deemed as high risk because the virus is circulating but is not linked to imported cases, he said.

“We need to quickly try to contain these zones where the virus circulates to prevent the disease from spreading to other zones,” he said, adding that a million of the city’s residents have been vaccinated so far.

Manufacturers of the vaccine include the Institut Pasteur, government factories in Brazil and Russia as well as French drugmaker Sanofi.

Congo’s outbreak, since January, comes at a time when political tensions linked to an upcoming presidential election and an economic crisis stoked by a slump in global commodity prices is already putting a huge strain on the country’s stability.

President Joseph Kabila is facing opposition, which has sometimes turned violent, amid concerns that he will try to cling to power beyond the expiry of his mandate at year-end.

(Writing by Tim Cocks; editing by Matthew Mpoke Bigg and G Crosse)