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Targeting mosquito sperm can help combat malaria

Anopheles Gambiae MosquitoScientists have discovered a way of reducing the fertility of malaria-carrying mosquitoes by targeting an enzyme that protects their sperm, potentially providing a new tactic to combat the disease.

Anopheles gambiae mosquitoes are the main transmitters of malaria, which affects  around 200 million people every year. The females mate only once during their lives.

They store the sperm from this single mating in an organ called the spermatheca, from which they repeatedly take sperm over the course of their lifetime to fertilise the eggs that they lay. The female needs the sperm to stay healthy whilst they are in storage in the spermatheca, so that they are viable each time she uses them to reproduce.

The new research shows that the sperm are partly protected by the actions of an enzyme called HPX15. When the researchers interfered with HPX15 in female A gambiae mosquitoes in the laboratory, the females fertilised fewer eggs and therefore produced fewer offspring. This is the first time that scientists have discovered a mechanism that preserves the function of sperm in A gambiae.

The researchers, from Harvard School of Public Health, the University of Perugia and Imperial College London, believe that their insight could ultimately lead to a new weapon in the fight against malaria. This would work by disabling HPX15 to reduce female fertility and through that, reduce the number of malaria-carrying mosquitoes in circulation.

“Malaria kills over 650,000 people every year and we need to find new ways of tackling it, partly because mosquitoes continue to evolve ways of resisting our efforts,” Dr Robert Shaw, one of the lead authors of the research, said.  “We are interested in cutting the numbers of malarial mosquitoes by impairing their ability to reproduce, and our new study suggests a way that we might be able to do this.

“There is no single magic bullet for tackling malaria, but making mosquitoes less fertile could provide us with a  valuable weapon against the disease,” said Shaw. The study suggests that HPX15 may protect the stored sperm against potentially damaging molecules called free radicals, which are particularly abundant after a female takes a blood feed.

Ensuring that the sperm are healthy after blood-feeding is important for the female’s fertility as she reproduces after each feed, fertilising her eggs with sperm released from the spermatheca. The study was published in the journal Proceedings of the National Academy of Sciences.

New malaria vaccine shows promise in clinical trials

VaccineA new malaria vaccine, which is being developed in the US, has shown promising results in early stage clinical trials, scientists say. Researchers found that high doses of the vaccine protected 12 out of 15 patients from the disease. The vaccine involves injecting live but weakened malaria-causing parasites directly into patients to trigger immunity.

“We were excited and thrilled by the result, but it is important that we repeat it, extend it and do it in larger numbers,” said lead author Dr Robert Seder, from the Vaccine Research Center at the National Institutes of Health, in Maryland. Previous research has found that exposure to mosquitoes treated with radiation can protect against malaria. But studies have shown that it takes more than 1,000 bites from the insects over time to build up a high level of immunity.

A US biotech company called Sanaria took lab-grown mosquitoes, irradiated them and then extracted the malaria-causing parasite (Plasmodium falciparum), all under the sterile conditions. These living but weakened parasites are then counted and placed in vials, where they can then be injected directly into a patient’s bloodstream. This vaccine candidate is called PfSPZ.

To carry out the Phase-1 clinical trial, the researchers looked at a group of 57 volunteers, none of whom had had malaria before. Of these, 40 received different doses of the vaccine, while 17 did not. They were then all exposed to the malaria-carrying mosquitoes, ‘BBC News’ reported. The researchers found that for the participants not given any vaccine, and those given low doses, almost all became infected with malaria.

However, for the small group given the highest dosage, only three of the 15 patients became infected after exposure to malaria. “Based on the history, we knew dose was important because you needed 1,000 mosquito bites to get protection – this validates that,” Seder said. “It allows us in future studies to increase the dose and alter the schedule of the vaccine to further optimise it. The next critical questions will be whether the vaccine is durable over a long period of time and can the vaccine protect against other strains of malaria,” he said. The results were published in the journal Science.

New vaccine adjuvant from ‘Ashwagandha’ gets US patent

PUNE: The US patent office has granted patent to an innovative industry-academia research project that has led to a new vaccine adjuvant extracted from ‘ Ashwagandha’, also known as Indian Ginseng, a medicinal plant used in Ayurveda as an immunity enhancer. The grant of patent will further the cause of development of far more effective vaccines meant for improvement of human immune system to counter various ailments.

The Union government’s department of science and technology (DST) had sponsored the research project which was jointly executed by Pune-based Serum Institute of India (SII) and University of Pune’s Inter-disciplinary School of Health Sciences (ISHS).

Executive director of SII Suresh Jadhav is the lead author while ISHS head Bhushan Patwardhan and SII research manager Manish Gautam formed the team of inventors. Additional research team included Sunil Gairola and Yojana Shinde from the SII, Dada Patil and Sanjay Mishra from the university.

Jadhav told TOI on Friday, “We are already in the process of developing new vaccines and the US patent will enable us the use the newly developed adjuvant right from the development stage of these vaccines. The new vaccine adjuvant has been found to be far more effective compared to traditional adjuvant. It has shown greater success in applications related to ailments like meningitis; diphtheria; and tetanus, among others,” he added.

According to Patwardhan, “The application of this new adjuvant can be envisaged not only with vaccines against meningitis, polio, diphtheria, tetanus and hepatitis but also holds promise against HIV, tuberculosis and malaria.” Patwardhan has described the project as a unique industry-academia partnership success story with a very high potential of applications owing to the involvement of the industry.

He said, “Newer vaccines include synthetic, recombinant or highly purified subunit antigens that are weakly immunogenic. Therefore vaccine formulations often require adjuvants for better immunological efficiency. Immuno-modulators obtained from different sources like synthetic, bacterial, viral have been used for enhancement of immune response to vaccines. Plant based products are being considered as one option for immune adjuvants.”

He said, “The concept of rasayana in Ayurveda is based on modulation of immune response to provide better immunity and resistance to fight against diseases. Many extracts and formulations prepared from rasayana plants have shown immuno-modulatory activity in various models. Researchers in health sciences have been actively engaged in establishing immuno-modulatory activity of medicinal plants including ‘Ashwagandha’,’Shatavari’ and ‘Guduchi.’ Our studies indicate that these botanical materials have potential to be developed as immuno-adjuvants. As such, it was desirable to develop well characterized and highly pure adjuvant as compared to crude extracts which can be formulated with vaccines.”

The DST had provided a total financial outlay of Rs 90 lakh spread over three years for the research project, which had completed in 2007 and actual development work continued thereafter at the SII. Following Indian patents, the US Patent application was made in 2009.

About ‘Ashwagandha’
The project was sponsored by the Union government’s department of science and technology

It was jointly executed Serum Institute of India and the University of Pune’s Inter-disciplinary School of Health Sciences

The US patent will enable researchers to use the adjuvant right from the development stage of the vaccine

The new vaccine adjuvant has been found to be far more effective compared to traditional adjuvant

Scientists say the adjuvant can applicable for vaccines against meningitis, polio, diphtheria, tetanus and hepatitis and also holds promise against HIV, tuberculosis and malaria

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