Scientists Are Getting Really Close to a Malaria Vaccine


A new candidate just proved 100% effective in clinical trials.

A new malaria vaccine candidate has proven up to 100 percent effective in clinical trials.

The potential vaccine introduces live malaria parasites into patients, paired with the medication needed to combat them. It was given to 67 healthy humans, and the nine participants given the highest dose were 100 percent protected against the disease for at least 10 weeks after vaccination.

This is only a Phase II clinical trial, aimed at looking at how well the vaccine works in a small group of healthy people, as well as testing the side effects.

But the most exciting part is that it’s not the only vaccine candidate currently proving itself in clinical trials.

Last year, the World Health Organisation (WHO) announced that a pilot programme involving the world’s first licensed malaria vaccine – RTS,S, also known as Mosquirix – would be rolled out in three sub-Saharan African countries in 2018.

Mosquirix has so far only proven up to 50 percent effective in children, but it’s hoped that further testing and dose tweaking in the pilot program could improve that efficacy further.

Now, another new vaccine candidate called Sanaria® PfSPZ-CVac has just cleared Phase II clinical trials. It’s not as far along in the drug development process as Mosquirix, but so far, it’s showing the potential to be a lot more effective.

Regardless of which one ultimately ends up offering better protection, the reality is that after more than a century, we’re finally getting really close to not just one, but two viable malaria vaccines hitting the market.

Malaria still kills more than 400,000 people each year – most of those in Africa – and nearly three-quarters of deaths in children under the age of five. WHO estimates that some 214 million people were infected in 2015 alone.

Being able to cheaply and effectively vaccinate vulnerable populations again the disease would save millions of lives.

But it’s a task that scientists have found challenging. Malaria is transmitted by a group of mosquito-borne parasites – most infections and deaths are caused by the particularly nasty parasite Plasmodium falciparum

Previous vaccine candidates, including Mosquirix, have been designed to protect the body against this threat by introducing it to different molecules from this parasite.

The hope is that this little ‘sneak preview’ would be enough to get the immune system to mount a full-blown attack on the next encounter, but so far, this approach hasn’t proven effective enough to offer 100 percent effective in humans.

Instead, the latest candidate to hit clinical trials has a different strategy.

Sanaria® PfSPZ-CVac is unusual, because it contains whole, live malaria parasite – not just parts of the pathogen or inactivated versions of it.

These live malaria parasites were injected into the body of trial participants alongside medication called chloroquine, which is known to kill the parasites.

This vaccine was given to 67 healthy adult participants, none of whom had ever had malaria before. Different doses of the vaccine candidate were tested, and the best protection was seen in nine people who were given the highest dose of the vaccine three times at four-week intervals.

Ten weeks after the trial, all nine of them had 100 percent protection from the disease. The researchers stopped actively measuring antibody response at that point, but the participants showed signs of ongoing protection after that.

“That protection was probably caused by specific T-lymphocytes and antibody responses to the parasites in the liver,” said Peter Kremsner, one of the researchers running the trial from the German Centre for Infection Research (DZIF).

The liver is particularly important in malaria infection, because after someone is bitten by an infected mosquito, the parasite spreads to the liver where it reproduces before exploding back into the body and causing malaria.

During that down-time in the liver, the immune system could shut down the infection, but the parasite isn’t making the patient sick as yet, so it doesn’t do anything.

Current medications, including chloroquine, treat the parasite as soon as it breaks out of the liver, but in order to properly protect against it we need to stop malaria before it gets to the liver in the first place.

By injecting people with an active parasite straight into their bloodstream, the new vaccine candidate is effectively mimicking the second part of the disease, giving the body a preview of what’s to come, so it can shut it down early next time.

“By vaccinating with a live, fully active pathogen, it seems clear that we were able to set off a very strong immune response,” said trial leader Benjamin Mordmueller.

“Additionally, all the data we have so far indicate that what we have here is relatively stable, long-lasting protection.”

The fact that the parasite is injected alongside chloroquine also meant that participants were protected from actually developing the disease – there were no signs of adverse effects on any of the test subjects.

While the group of nine people given the highest dose had the best protection against the disease, the lower doses given to other groups achieved efficacy of between 33 and 67 percent.

But while this trial was promising, so far, all the team has shown is that the vaccine works in high doses, and doesn’t cause side effects over a 10-week period.

The next step is to test the vaccine’s effectiveness over several years – which will happen in a phase III clinical trial in the African nation of Gabon that’s already been planned and funded by DZIF.

Mosquirix has completed phase III clinical trials, and in 2018, will be tested on the general public by WHO.

Only time will tell how successful either of these vaccines will be in the long-term. But drug development is an incredibly lengthy and expensive process, and it seems that when it comes to a malaria vaccine, we’re finally getting to the pointy end.

And that’s definitely worth celebrating.

World’s first malaria vaccine could be available by October


The world’s first viable malaria vaccine could be available by as early as October, after final trial results showed it can potentially prevent millions of cases of the deadly disease every year.

The vaccine candidate (RTS,S/AS01) is the first to reach phase 3 clinical testing and is partially effective against clinical disease in young African children up to 4 years after vaccination, according to final trial data published in The Lancet journal.

The results suggest that the vaccine could prevent a substantial number of cases of clinical malaria, especially in areas of high transmission.

The findings show that vaccine efficacy against clinical and severe malaria was better in children than in young infants, but waned over time in both groups.

However, protection was prolonged by a booster dose, increasing the average number of cases prevented in both children and young infants.
“Over 3 years of follow-up, an average 558 cases were averted for every 1,000 infants vaccinated, and 983 cases in those also given a booster dose,” said Greenwood.

The results suggest that the vaccine could prevent a substantial number of cases of clinical malaria, especially in areas of high transmission.

“Given that there were an estimated 198 million malaria cases in 2013, this level of efficacy potentially translates into millions of cases of malaria in children being prevented,” Greenwood added.

In 2014, initial phase 3 results at 18 months showed vaccine efficacy of about 46 per cent against clinical malaria in children and around 27 per cent among young infants.

“The European Medicines Agency (EMA) will assess the quality, safety, and efficacy of the vaccine based on these final data. If the EMA gives a favourable opinion, WHO could recommend the use of RTS,S/AS01 as early as October this year. If licensed, RTS,S/AS01 would be the first licensed human vacc ..

Zapped malaria parasite raises vaccine hopes.


Maverick malaria vaccine achieves 100% protection using parasites from irradiated mosquitoes.

Image

A malaria vaccine has become the first to provide 100% protection against the disease, confounding critics and far surpassing any other experimental malaria vaccine tested. It will now be tested further in clinical trials in Africa.

The results are important because they demonstrate for the first time the concept that a malaria vaccine can provide a high level of protection, says Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, adding that the findings are cause for “cautious optimism”.

No effective malaria vaccine is available at present. The World Health Organization has set a target to develop a malaria vaccine with 80% efficacy by 2025, but until now, says Fauci, “we have not even gotten anywhere near that level of efficacy.”

Scientists had previously been sceptical of the vaccine because producing it required overcoming massive logistical hurdles. The vaccine — called PfSPZ because it is made from sporozoites (SPZ), a stage in the life cycle of the malarial parasite Plasmodium falciparum (Pf) — uses a weakened form of the whole parasite to invoke an immune response.

In the phase I safety trial, reported today in Science1, the six subjects given five doses intravenously were 100% protected from later challenge by bites of infectious mosquitoes, whereas five of six unvaccinated controls developed malaria — as did three of nine people given only four doses of the vaccine.

PfSPZ was developed by Sanaria, a company based in Rockville, Maryland, and led by Stephen Hoffman, a veteran malaria researcher who also led the PfSPZ clinical trial. Most malaria-vaccine candidates are recombinant-subunit vaccines containing just a handful of parasite proteins, but Hoffman decided to test the whole-sporozoite vaccine on the basis of past experiments dating back to the 1970s showing that strong and long-lived protection could be obtained by exposing volunteers to thousands of bites from irradiated infected mosquitoes2.

That the vaccine works so well is a “pivotal success,” says Stefan Kappe, a malaria researcher at the Seattle Biomedical Research Institute in Washington.”The trial results constitute the most important advance in malaria vaccine development since the first demonstration of protection with radiation attenuated sporozoite immunization by mosquito bite in the 70s.”

Against the odds

But to make PfSPZ was challenging. Sanaria succeeded in raising mosquitoes in sterile conditions on an industrial scale, feeding them blood infected with the malaria parasite and then irradiating them to weaken the parasite so that it can still infect people but not cause disease.

Billions of parasites were then harvested from the mosquitoes’ salivary glands, purified and cryopreserved. Many researchers were highly sceptical that sporozoites could be mass-produced in a way that passed the strict quality and safety standards needed for human medicines, notes Fauci. “To my amazement, Hoffman did it,” he adds.

Hoffman says that he hopes to have a vaccine licensed within four years. The trial now needs to be repeated and extended in regions where malaria is rampant to test whether it provides protection against different strains of the parasite than that used in the vaccine, and to see how it performs in different age groups, including young children. The first trials will be carried out at the Ifakara Health Institute in Tanzania.

Piggybacking infrastructure

Even if the vaccine is shown to be highly effective in the field, logistical difficulties might limit its applicability. In mass vaccination campaigns, hundreds of people are vaccinated within minutes, so vaccines are usually given orally or by injection into or just under the skin. Intravenous injection is more cumbersome. “It’s very unlikely to be deployable in infants or young children,” argues Adrian Hill, a malaria researcher at the Jenner Institute in Oxford, UK.

In 2011, a clinical trial of PfSPZ given under the skin reported disappointing results, protecting only two of 80 subjects3. But the need to deliver the vaccine intravenously “is not a show-stopper”, says Hoffman, noting that the volume of vaccine —  0.5 millilitres — is tiny and requires a tiny syringe, although the company is exploring ways to improve the intravenous delivery system.

Another logistical hurdle, says Hill, is that the vaccine must be kept frozen in liquid nitrogen vapour phase. Hoffman argues, however, that the vaccine can piggyback on veterinary infrastructure in places that use liquid nitrogen to store and transport veterinary vaccines and semen for artificial insemination of livestock. “If you can carry semen into the deep Saharan belt and remote areas, why can’t you do that for a human vaccine?” says Marcel Tanner, director of the Swiss Tropical and Public Health Institute in Basel, Switzerland, which is a sponsor of the trial in Tanzania.

“Which of the logistical challenges can be managed and which will become show-stoppers can be difficult to predict,” says David Kaslow, director of the PATH Malaria Vaccine Initiative in Washington, DC, a public–private partnership for malaria-vaccine development.

Kappe hopes the trial results will encourage funders to invest more in optimizing this vaccine approach. “If we were talking about an HIV vaccine, there would be no question about investing in this type of success,” he says.

Source: Nature

Time for the Big Push to Defeat Malaria.


Moments of historic greatness are rarely realized by a single actor. Instead, they require the work of partners, with a sense of shared responsibility and coordinated action. The Big Push to defeat malaria is no different. In the past 10 years, partners working together have reversed malaria’s spread and prevented millions of deaths, mostly of children under the age of five. Yet even with all that progress, malaria still claims a child’s life every minute. So we have more work to do. Science has given us the tools to defeat this disease. We will achieve greatness by getting it done.

Today we have insecticide-treated nets rather than just regular nets that last longer, significantly reducing costs. There are new drugs to tackle resistant strands and rapid diagnostic tests that allow us to identify kids that do and don’t have malaria. We are moving in the right direction. Global malaria mortality rates have dropped by 26 percent and half of the malaria endemic countries are on track to meeting the global target of reducing malaria case incidence by 75 percent by 2015.

As a global community, our fates are often more intertwined than we like to imagine. Controlling malaria isn’t only a prospect of preventing needless deaths, it is an economic imperative. Entrepreneurs, farmers and traders who are at home sick themselves or with their kids cost Africa an estimated $12 billion a year in productivity. Defeating malaria is one of the first steps we can take to speed up Africa-driven economic growth.

Later this year, the international community will gather to pledge money to the Global Fund for the next three years. In April, the Global Fund requested $15 billion from donors as an investment towards the historical opportunity of defeating these diseases. It’s the kind of investment where the return will be measured in lives saved, and the increased productivity of developing countries no longer burdened by deaths from mosquito bites.

Essential to maximizing these investments, African leaders will continue to demonstrate their own commitment to national health programs both financially and with human resources. The African Leaders Malaria Alliance, a consortium of 49 leaders from the continent, tracks country progress in preventing and treating the disease, with government leaders holding one another accountable to keep malaria a priority, while working towards the goal of near zero deaths by the end of 2015.

With less than 1,000 days until the clock runs out on the 2015 Millennium Development Goals, our resolve will be tested both before and after the zero hour. Meeting the health related MDGs would no doubt be a great accomplishment for our global brothers and sisters, but history will judge us by whether or not we fill our war chest and use our proven strategies and tools to defeat these diseases. As partners in this fight, this is our shared opportunity and responsibility.

Source: huffingtonpost.com

 

 

 

 

Tests find malaria vaccine useful.


A malaria vaccine tested on infants in seven African countries has shown a protective effect that is small but possibly enough to prove useful in areas where the infection is a serious threat to children.

The vaccine, known officially as RTS,S/AS01, reduced by 33 percent the number of cases of malaria suffered by infants in the year after they were immunized, according to a study presented in South Africa on Friday and published online by the New England Journal of Medicine.

The actual number of infections was small. About 2.3 percent of babies not getting the vaccine suffered a case of severe malaria in their first year. The vaccine reduced that by one-third.

Preventive measures and better treatment have driven down malaria mortality over the past 20 years. Nevertheless, the mosquito-borne infection still causes about 216 million cases of illness and 655,000 deaths — almost all of them of African children — each year.

“If you broadly implement this across sub-Saharan Africa, it is going to prevent millions of cases and save thousands of lives,” said David Kaslow, director of the malaria vaccine initiative at the Program for Appropriate Technology in Health (PATH), a nonprofit group in Seattle that is helping run the vaccine trials.

One of the more successful tools against malaria is the insecticide-treated bed net. Studies have shown that consistently sleeping under one reduces cases of malaria by 25 to 75 percent. About 85 percent of the children in the vaccine study slept under a net, so they were substantially protected. In addition, indoor spraying with long-lasting pesticides — another preventive tool — was common in four of the 11 study areas.

The study enrolled infants in Kenya, Tanzania, Mozambique, Malawi, Ghana, Burkina Faso and Gabon. Malaria transmission differed greatly from place to place. In the worst area, babies averaged two bouts of malaria a year. In the site with the least transmission, the figure was one-hundredth that rate.

About 6,500 babies were randomly assigned to get the malaria vaccine or an unrelated one that helps prevent bacterial meningitis. By design, twice as many were assigned to the malaria vaccine as to the other one. The malaria vaccine was given in three shots a month a part, starting at two months of age.

At least one episode of severe malaria occurred in 2.3 percent of the babies getting the meningitis vaccine, compared with 1.5 percent in those getting the malaria vaccine.

Death from any cause, including malaria, was rare. It occurred in 1.5 percent of the babies who got the malaria vaccine and 1.3 percent in those who got the meningitis vaccine.

Meningitis was twice as likely in the malaria-vaccine babies. Whether that was because they didn’t get the meningitis vaccine or happened by chance is unknown.

A study of the same vaccine in children 5 to 17 months of age was reported last year. It found a bigger protective effect — about 50 percent.

The vaccine is made by GlaxoSmithKline. The company has said the price of the vaccine will cover the cost of its production and a 5 percent margin, which will be reinvested in research on other vaccines for tropical diseases.

Source: http://www.washingtonpost.com

 

 

Malaria Vaccine A Letdown For Infants.


An experimental malaria vaccine once thought promising is turning out to be a disappointment, with a new study showing it is only about 30 percent effective at protecting infants from the killer disease.

That is a significant drop from a study last year done in slightly older children, which suggested the vaccine cut the malaria risk by about half – though that is still far below the protection provided from most vaccines. According to details released on Friday, the three-shot regimen reduced malaria cases by about 30 percent in infants aged 6 to 12 weeks, the target age for immunization.

Dr. Jennifer Cohn, a medical coordinator at Doctors Without Borders, described the vaccine’s protection levels as “unacceptably low.” She was not linked to the study.

Scientists have been working for decades to develop a malaria vaccine, a complicated endeavor since the disease is caused by five different species of parasites. There has never been an effective vaccine against a parasite. Worldwide, there are several dozen malaria vaccine candidates being researched.

In 2006, a group of experts led by the World Health Organization said a malaria vaccine should cut the risk of severe disease and death by at least half and should last longer than one year. Malaria is spread by mosquitoes and kills more than 650,000 people every year, mostly young children and pregnant women in Africa. Without a vaccine, officials have focused on distributing insecticide-treated bed nets, spraying homes with pesticides and ensuring access to good medicines.

In the new study, scientists found babies who got three doses of the vaccine had about 30 percent fewer cases of malaria than those who didn’t get immunized. The research included more than 6,500 infants in Africa. Experts also found the vaccine reduced the amount of severe malaria by about 26 percent, up to 14 months after the babies were immunized.

Scientists said they needed to analyze the data further to understand why the vaccine may be working differently in different regions. For example, babies born in areas with high levels of malaria might inherit some antibodies from their mothers which could interfere with any vaccination.

“Maybe we should be thinking of a first-generation vaccine that is targeted only for certain children,” said Dr. Salim Abdulla of the Ifakara Health Institute in Tanzania, one of the study investigators.

Results were presented at a conference in South Africa on Friday and released online by the New England Journal of Medicine. The study is scheduled to continue until 2014 and is being paid for by GlaxoSmithKline and the PATH Malaria Vaccine Initiative.

“The results look bad now, but they will probably be worse later,” said Adrian Hill of Oxford University, who is developing a competing malaria vaccine. He noted the study showed the Glaxo vaccine lost its potency after several months. Hill said the vaccine might be a hard sell, compared to other vaccines like those for meningitis and pneumococcal disease – which are both effective and cheap.

“If it turns out to have a clear 30 percent efficacy, it is probably not worth it to implement this in Africa on a large scale,” said Genton Blaise, a malaria expert at the Swiss Tropical and Public Health Institute in Basel, who also sits on a WHO advisory board.

Eleanor Riley of the London School of Hygiene and Tropical Medicine, said the vaccine might be useful if used together with other strategies, like bed nets. She was involved in an earlier study of the vaccine and had hoped for better results. “We’re all a bit frustrated that it has proven so hard to make a malaria vaccine,” she said. “The question is how much money are the funders willing to keep throwing at it.”

Glaxo first developed the vaccine in 1987 and has invested $300 million in it so far.

WHO said it couldn’t comment on the incomplete results and would wait until the trial was finished before drawing any conclusions.

RTS,S/AS01 Vaccine Reduces Malaria Incidence by Half.


Initial results from a phase III trial show protection against clinical and severe malaria during the 12 months after vaccination in children aged 5 to 17 months.

Early trials of the RTS,S/AS01 malaria vaccine have shown approximately 50% efficacy. Now, this vaccine is being evaluated in a manufacturer-sponsored, double-blind, multicenter, phase III trial in Africa, among children in two age groups: 6 to 12 weeks and 5 to 17 months.

Children at 11 centers in seven African countries (6537 in the younger age group; 8923 in the older group) were randomized to receive three intramuscular doses of RTS,S/AS01 or a comparator vaccine at monthly intervals. In the younger children, the comparator vaccine was meningococcal C conjugate vaccine; in the older group, it was rabies vaccine.

In an interim (12-month) efficacy analysis conducted among the first 6000 children enrolled in the older age group, vaccine efficacy against clinical malaria was 50.4% in the intent-to-treat population and 55.8% in the per-protocol population. Efficacy against severe malaria was 45.1% and 47.3%, respectively. (Efficacy against severe malaria in the 2 age groups combined was lower — 34.8% — during an average follow-up of 11 months.)

In the interim safety analysis, meningitis was significantly more common in the RTS,S/AS01 group than in the control group for both age categories. In the older age category, 10 children in the RTS,S/AS01 group had at least one vaccine-related serious adverse event, including seven seizures (rate, 1.04 per 1000 doses), compared with only 1 child in the control group (who also had a seizure). The proportions of children dying and the causes of death were similar between the RTS,S/AS01 and control groups in the 5–17 month category.

Comment: Overall, these results support the findings of earlier studies. Contrary to expectations, however, no reduction was observed in malaria-related or all-cause mortality in the RTS,S/AS01 group. The authors attribute this finding to a very low rate of malaria-specific mortality in the overall study population during the course of the trial. Continued monitoring of meningitis is needed to assess whether the increase in the RTS,S/AS01 group persists. Other key questions (including duration of protection and cost) also remain unanswered. Nonetheless, as noted by an editorialist, the WHO has already indicated that it could recommend vaccine use in some areas as early as 2015 — after the full results from this trial (available in 2014) have been analyzed. Although reductions in malaria episodes and deaths have been achieved through current interventions, the addition of an effective malaria vaccine to available tools could hasten control and would be especially valuable if resistance to current first-line drugs increases.

source: Journal Watch Infectious Diseases

New approach to malaria vaccine revealed by Oxford researchers


A potential new malaria vaccine has shown promise in animal studies, according to research.

An Oxford University team is to start safety trials in human volunteers after lab tests showed the vaccine works against all strains of the parasite.

UK scientists recently found the route malaria uses to enter blood cells.

They hope to target this pathway in a new approach to developing a vaccine against malaria, which kills hundreds of thousands of people a year.

Several potential malaria vaccines are already being tested in clinical trials; although no vaccine has yet been licensed for use.

Early clinical trials in Africa suggest a vaccine known as RTS,S appears to protect about half of people vaccinated from malaria.

While these results are encouraging, some scientists believe a more effective vaccine is needed to fight the disease.

One possibility is to exploit a recently-discovered potential weakness in the parasite’s life cycle.

A team at the Sanger Institute found in November that a single receptor on the surface of red blood cells and a substance known as “PfRh5” on the parasite are crucial to the success of malaria in invading blood cells.

Malaria

  • Malaria killed about 781,000 people in 2009, mainly children and pregnant women, according to the World Malaria Report 2010
  • Malaria is caused by parasites injected into the bloodstream by infected mosquitoes
  • The most deadly form, Plasmodium falciparum, is responsible for nine out of 10 deaths from malaria
  • Vaccinating against malaria is thought to be the best way to protect populations against the disease
  • No licensed vaccine is currently available.
  • Source: Wellcome Trust

Early lab tests suggest a vaccine against the protein may prove effective, at least in animals.

Dr Sandy Douglas is a Wellcome Trust Clinical Research Training Fellow from the University of Oxford and first author on the study, published in the journal, Nature Communications.

He told the BBC: “We have found a way of making antibodies that kill all different strains of malaria parasites. This is still early phase research in animals. The next step is to do clinical trials in people.”

If safety tests of the vaccine prove successful, clinical trials in patients could begin within the next two to three years, says the Oxford team.

Dr Gavin Wright, from the Wellcome Trust Sanger Institute, said recent findings on how the malaria parasite invades red blood cells were unexpected.

Dr Wright, a co-author on both studies, added: “It revealed what we think is the parasite’s Achilles heel in the way it invades our cells and provided a target for potential new vaccines.”

Source:BBC medicine.

 

 

A Fungal ‘Vaccine’ for Malaria-Carrying Mosquitoes


Researchers have genetically modified a fungus so that it attacks the malaria parasite within a mosquito. They hope the fungus’s spores, applied to the walls of houses or mosquito traps, could help stop the spread of the disease in an environmentally friendly way.

Fungi that attack insects are present in soils worldwide, and they are used in gardens, greenhouses, and open fields to control agricultural pests. In 2005, scientists showed that strains of two different fungi, Beauveria bassiana and Metarhizium anisopliae, could attack the mosquitoes that spread malaria. When the fungal spores come in contact with the mosquito’s exoskeleton, they bore their way into the hemolymph—the insect’s equivalent of blood—where they grow, ultimately killing the mosquito.

But the fungi take about 2 weeks to kill the insects. “They want to kill slowly, extracting as many nutrients as possible so they can produce more spores,” says Raymond St. Leger, an entomologist at the University of Maryland, College Park. Because it takes only 12 to 14 days for the malaria parasite to mature into its infective form inside the mosquito, an insect often has time to spread the parasite before a fungal infection has killed it off, especially if the mosquito is exposed to the fungus several days after it picks up the parasite.

St. Leger and his colleagues originally created a genetically modified version of the fungus M. anisopliae that, thanks to the insertion of an insect-specific neurotoxin, kills mosquitoes more quickly. But a quick kill also has a disadvantage: It can lead to mosquitoes that are resistant to the fungus, because the resistant insects are the only ones who survive long enough to reproduce.

Now St. Leger and his colleagues have engineered strains of M. anisopliae to block the malaria parasite from developing inside the infected mosquito. Online today in Science, they describe inserting different combinations of three different genes into the fungus to block the malaria parasite from entering the mosquito’s salivary glands. (Parasites from the salivary glands infect new hosts when an infected mosquito bites a new victim.) One gene codes for a peptide—a short piece of a protein—called SM1 that resembles the parasite protein the parasite uses to enter the salivary glands. The copies of SM1 produced by the fungus block the parasite’s way in. Another added gene codes for part of a human antibody that binds to the parasites and causes them to clump together. A third is an antimicrobial protein called scorpine—it was found in scorpions—that kills the malaria parasite.

When the researchers sprayed spores of the genetically modified fungus strains onto mosquitoes in the lab, the spores did not kill the insects faster than the normal fungus did. But they did significantly reduce the number of parasites in the mosquitoes’ salivary glands: Six days after receiving spores of the genetically modified strains, the mosquitoes had 98% fewer parasites in their salivary glands than did those treated with normal fungus.

And the genetically modified fungus acts quickly. After giving mosquitoes a malaria-infected blood meal, the researchers waited 11 days before spraying some with normal fungal spores and others with the enhanced spores. Two days later, 86% of fungus-free mosquitoes could transmit malaria, as could 72% of the insects infected with normal fungus, but only 20% of the mosquitoes exposed to the transgenic fungus could do so.

The results are impressive, says Marit Farenhorst, who studies insect-attacking fungi at In2Care, a start-up company in Wageningen, the Netherlands. “In case you are a little bit late in getting the mosquito infected in field, you can still be in time to affect the transmission of malaria,” she says. “It’s kind of like vaccinating the mosquito.” The main drawback of the approach, says Farenhorst, is that fungal spores survive only a few months when applied to walls or other surfaces. It’s currently impractical and expensive to have to keep reapplying spores. But several teams are working on better ways to apply the spores and keep them alive, she says.

Although St. Leger acknowledges that widespread suspicion of genetically modified organisms might make it more difficult to persuade people to apply the fungus in their houses, he says the approach is extremely low risk: The fungus strain that the scientists modified infects only mosquitoes, the genes they inserted only recognize human malaria, and the genes are only turned on once the fungus is inside the mosquito. None of the genes give the fungus a survival advantage over the wild strains that are common in soils, he says. Still, St. Leger says, completing relevant safety tests will take several years.

source: science now