WHO backs rollout of malaria vaccine for African children

By Maggie Fick and Aaron Ross

NAIROBI (Reuters) -The World Health Organization (WHO) said on Wednesday the only approved vaccine against malaria should be widely given to African children, potentially marking a major advance against a disease that kills hundreds of thousands of people annually.

The WHO recommendation is for RTS,S – or Mosquirix – a vaccine developed by British drugmaker GlaxoSmithKline.

Since 2019, 2.3 million doses of Mosquirix have been administered to infants in Ghana, Kenya and Malawi in a large-scale pilot program coordinated by the WHO. The majority of those whom the disease kills are aged under five.

That program followed a decade of clinical trials in seven African countries.

“This is a vaccine developed in Africa by African scientists and we’re very proud,” said WHO director-general Tedros Adhanom Ghebreyesus.

“Using this vaccine in addition to existing tools to prevent malaria could save tens of thousands of young lives each year,” he added, referring to anti-malaria measures like bed nets and spraying.

Malaria is far more deadly than COVID-19 in Africa. It killed 386,000 Africans in 2019, according to a WHO estimate, compared with 212,000 confirmed deaths from COVID-19 in the past 18 months.

The WHO says 94% of malaria cases and deaths occur in Africa, a continent of 1.3 billion people. The preventable disease is caused by parasites transmitted to people by the bites of infected mosquitoes; symptoms include fever, vomiting and fatigue.

The vaccine’s effectiveness at preventing severe cases of malaria in children is only around 30%, but it is the only approved vaccine. The European Union’s drugs regulator approved it in 2015, saying its benefits outweighed the risks.

“This is how we fight malaria, layering imperfect tools on top of each other,” said Ashley Birkett, who leads global malaria vaccine work at Path, a non-profit global health organization that has funded the development of the vaccine with GSK and the three-country pilot.

Another vaccine against malaria, developed by scientists at Britain’s University of Oxford and called R21/Matrix-M, showed up to 77% efficacy in a year-long study involving 450 children in Burkina Faso, researchers said in April, but it is still in the trial stages.

GSK also welcomed the WHO recommendation.

“This long-awaited landmark decision can reinvigorate the fight against malaria in the region at a time when progress on malaria control has stalled,” Thomas Breuer, Chief Global Health Officer, said in a statement.

GSK shares held steady in New York following the announcement, which came after the close of trading in its London-listed shares.

FUNDING CHALLENGE

The recommendation was jointly announced in Geneva by the WHO’s top advisory bodies for malaria and immunization, the Malaria Policy Advisory Group and the Strategic Advisory Group of Experts on Immunization.

Experts said the challenge now would be mobilizing financing for production and distribution of the vaccine to some of the world’s poorest countries.

GSK has to date committed to produce 15 million doses of Mosquirix annually, in addition to the 10 million doses donated to the WHO pilot programs, up to 2028 at a cost of production plus no more than 5% margin.

A global market study led by the WHO this year projected demand for a malaria vaccine would be 50 to 110 million doses per year by 2030 if it is deployed in areas with moderate to high transmission of the disease.

The GAVI vaccine alliance, a global public-private partnership, will consider in December whether and how to finance the vaccination program.

“As we’ve seen from the COVID vaccine, where there is political will, there is funding available to ensure that vaccines are scaled to the level they are needed,” said Kate O’Brien, Director of WHO’s Department of Immunization, Vaccines and Biologicals.

A source familiar with planning for the vaccine’s development said the price per dose was not yet set, but would be confirmed after GAVI’s funding decision and once there is a clear sense of demand for the vaccine.

The WHO’s decision had personal meaning for Dr. Rose Jalong’o, a vaccinology specialist at the Kenyan health ministry.

“I suffered from malaria as a child and during my internship, and during my clinical years I attended to children in hospital because of severe malaria who needed blood transfusion and unfortunately some of them died.”

“It’s a disease I have grown up with and, seeing all this in my lifetime, it’s an exciting time.”

(Reporting by Maggie Fick in Nairobi and Aaron Ross in Dakar; Editing by Katharine Houreld, Mark Potter and Emelia Sithole-Matarise)

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)