WASHINGTON: Scientists have discovered how the immune system makes a powerful antibody that blocks HIV infection of cells by targeting a key site, paving way for an effective vaccine for the deadly virus.
Researchers believe that if a vaccine could elicit potent antibodies to a specific conserved site in the V1V2 region of the virus, one of a handful of sites that remains constant on the fast-mutating virus, then the vaccine could protect people from HIV infection.
Analyses of the results of a clinical trial of the only experimental HIV vaccine to date to have modest success in people suggest that antibodies to sites within V1V2 were protective.
The new findings point the way towards a potentially more effective vaccine that would generate V1V2-directed HIV neutralising antibodies, researchers said.
The study led by the National Institute of Allergy and Infectious Diseases ( NIAID) scientists began by identifying an HIV-infected volunteer who naturally developed V1V2-directed HIV neutralising antibodies, named CAP256-VRC26, after several months of infection.
Using techniques similar to those employed in an earlier study of HIV-antibody co-evolution, the researchers analysed blood samples donated by the volunteer between 15 weeks and 4 years after becoming infected.
This enabled the scientists to determine the genetic make-up of the original form of the antibody; to identify and define the structures of a number of the intermediate forms taken as the antibody mutated towards its fullest breadth and potency.
It also allowed them to describe the interplay between virus and antibody that fostered the maturation of CAP256-VRC26 to its final, most powerful HIV-fighting form.
The study showed that after relatively few mutations, even the early intermediates of CAP256-VRC26 can neutralise a significant proportion of known HIV strains.
This improves the chances that a V1V2-directed HIV vaccine developed based on the new findings would be effective, according to scientists, who have begun work on a set of vaccine components designed to elicit V1V2 neutralising antibodies and guide their maturation.
Scientists have discovered a mechanism that helps HIV evade antibodies and stabilise key proteins, a finding that could pave way for more effective vaccine for the deadly virus.
National Institutes of Health (NIH) scientists found the mechanism involved in stabilising key HIV proteins and thereby concealing sites where some of the most powerful HIV neutralising antibodies bind.
Numerous spikes jut out of the surface of HIV, each containing a set of three identical, bulb-shaped proteins called gp120 that can be closed together or spread apart like the petals of a flower, researchers said.
Some of the most important sites targeted by HIV neutralising antibodies are hidden when the three gp120s, or the trimer, are closed, and the gp120 trimer remains closed until the virus binds to a cell, they said.
The researchers discovered that certain amino acids located on the gp120 protein undergo a process that stabilises the trimer in its closed position.
In this process, called sulfation, the amino acids acquire a sulfur atom surrounded by four oxygen atoms.
By either blocking or increasing sulfation of these amino acids, the researchers changed the sensitivity of the virus to different neutralising antibodies, indicating that the trimer was being either opened or closed.
The scientists suggest that if the synthesised gp120 widely used in HIV research were fully sulfated during manufacture, the resulting product would adopt a more true-to-life structure and more closely mirror the way the immune system sees unbound HIV.
This might help generate a more effective HIV vaccine, NIH researchers said.
They added that full sulfation of gp120 may enable scientists to crystallise the molecule more readily, which also could advance HIV vaccine design.
From being a death sentence, HIV/AIDS has now evolved as a chronic yet manageable disease, with early and effective treatment utilising anti-retroviral drugs.
Thus, even as the State continues to focus on the goal of preventing new HIV infections in the general population, the major challenge in the coming years would be ensuring continued care and support services for those who are surviving with the infection.
“Kerala’s HIV prevalence rate has further come down, from last year’s 0.19 per cent to 0.12 per cent this year. The total estimated number of those living with HIV in the State is 25,090. We have achieved almost zero transmission of the infection from mother to child; the infection among those groups considered to be high-risk is also coming down because of our intensive programmes. But high-risk behaviour of those in the general population has been resulting in new infections,” a senior official working in the area of HIV/AIDS said.
“Our focus will soon shift exclusively to the issues faced by those living with HIV because the anti-retroviral therapy (ART) has made it possible for them to live normal lives.
“When the State began offering free ART in 2004, the strategy had been to start treatment when the CD4 count reached 200. (CD4 is the cell count indicating the stage of HIV infection when drugs should be started). In the last two years, we raised the CD 4 cut-off to 350 and soon it will be made 500. This means that we are offering treatment very early to HIV +ve
persons,” said M. Prasannakumar, former head of the technical support unit for the Kerala State AIDS Control Society.
Early ART is now a major strategy to prevent new infections in the community because the transmission potential of the virus when a person is on ART is very low, he said.
According to KSACS, HIV prevalence rates among targeted high-risk groups have been coming down steadily, especially among the injecting drug users (IDU) and female sex workers.
“The IDU group has been a concern, but we have now started oral opiod substitution therapy in over 10 government hospitals and the infectio
n rate amongst the group is coming down. Influx of migrant workers — we have some 25 lakh in the State — could be a concern but we can also seek relief in the fact that they are all from the low-prevalence States of West Bengal, Assam, and Orissa,” Dr. Prasannakumar said.
But the euphoria over the State’s successes should not result in complacence in the health system because new infections have not totally disappeared in the
State, warns Ajithkumar, Professor of Dermatology, Thrissur Medical College.
Scientists have actually identified a new type of boredom that they call apathetic boredom which is described as an unpleasant form of the emotion that resembles helplessness or depression. According to scientists, there are four kinds of boredom based on levels arousal. Till now scientists had identified four kinds of boredom:
Indifferent boredom: A state where a person feels relaxed, withdrawn and indifferent to their surroundings.
Calibrating boredom: Uncertain boredom but receptive to change or distraction.
Searching boredom: When a person’s restless and is looking for change or a distraction.
Reactant boredom: When a person is motivated to leave a situation for specific alternatives.
Now researchers claim to have identified a fifth type called apathetic boredom which is somewhat similar to a feeling of helplessness and/or depression. It is associated with low arousal levels and high levels of aversion.
Goetz and researchers conducted two real-time experience studies over two weeks among 63 German university students and 80 German high school learners. Participants had to complete digital questionnaires through the course of a day on a Personal Digital Assistant device about their activities and experiences.
Because of the assumed link between boredom and depression, the research group found it alarming that apathetic boredom was reported relatively frequently by 36% of the high school students sampled. The findings showed that the five boredom types do not just depend on the intensity of the boredom being felt, but mainly on the real-life situation in which it is experienced. Another interesting realisation is that people do not just randomly experience the different boredom types over time, but that they tend to experience one type. ‘We therefore speculate that experiencing specific boredom types might, to some degree, be due to personality-specific dispositions,’ said Goetz. The study has been published in Springer’s journal Motivation and Emotion.
What is depression?
As an illness, depression is as debilitating as a heart disease or HIV/AIDS. Those who suffer from the condition often describe the feeling as having a black cloud over their heads, which prevents them from enjoying anything or even functioning normally. One out of 20 people in the world suffer from depression but sadly many of them are forced to live in denial about the disease.
So how is depression different from sadness?
Sadness is part of the life without which happiness would have no meaning. To feel sad during major life crises like the death of a loved one, losing a job or the ending of a relationship is normal. Depression on the other hand is a condition where there is prolonged sadness and an individual’s mood isn’t tied to life events. While healthy individuals have moods related to life events, people suffering from depression suffer from disproportionate amount of sadness and guilt. It is a serious medical condition in which the symptoms make it difficult for the person to function in society, often leads to poor physical health and severe emotional pain.
How common is depression?
One out of every 20 people you know probably suffers from depression. The numbers are hard to pin down for a mental illness like depression because the symptoms are seen as a continuation of everyday-life behaviour. However, considering that 1.8 lakh Indians commit suicide every year and there are 20 times more attempts, which mean at least 36 lakh people in India are surely suffering from major depressive disorder.
Panama City: A top UN official said the global AIDS epidemic could be over by 2030 because of progress made in treatment and control of the disease.
“I think that 2030 is a viable target to say that we have reached the end of the epidemic,” said Luis Loures, a deputy executive director of UNAIDS, the UN agency leading the fight against HIV/AIDS.
“HIV will continue existing as a case here or there but not at the epidemic level we have today,” he told journalists yesterday.
Three million new HIV infections are reported each year and the disease, which attacks the immune system, kills 1.7 million people a year.
“We can get to the end of the epidemic because we have treatments and ways to control the infection,” said Loures, who is in Panama to discuss AIDS strategy with UN agencies in Latin America. “We are making progress, without a doubt.”
Two decades ago the average annual cost of treatment per person with HIV was USD 19,000 while today it is USD 150 thanks to generic drugs.
Moreover, people with HIV are getting treatment earlier, which retards the disease’s development.
According to UNAIDS, the annual incidence of new infections has fallen 20 per cent over the past decade, and in 25 countries, including 13 in sub-Saharan Africa, it has fallen by 50 per cent.
Over the past two years, the number of people who have obtained treatment for HIV has increased by 60 per cent.
“The challenge is now for the most vulnerable groups,” like homosexual males, sex workers and drug users who do not seek treatment for fear of being stigmatised or criminally prosecuted, Loures said.
“If we do not succeed in controlling the epidemic among these groups, AIDS will stay with us,” he warned.
At the end of 2011, there were 34 million people living with HIV, 69 percent of them in sub-Saharan Africa where one in 20 adults have the disease.
“Today, there are a number of cases where we have evidence of a cure and that gives us great hope,” Loures said.
Research published in the journal Nature has shown that vaccinated monkeys can clear Simian Immunodeficiency Virus (SIV) infection from their bodies.
It was effective in nine of the 16 monkeys that were inoculated.
The US scientists say they now want to use a similar approach to test a vaccine for HIV in humans.
Prof Louis Picker, from the Vaccine and Gene Therapy Institute at Oregon Health and Science University, said: “It’s always tough to claim eradication – there could always be a cell which we didn’t analyse that has the virus in it. But for the most part, with very stringent criteria… there was no virus left in the body of these monkeys.”
Search and destroy
The research team looked at an aggressive form of virus called SIVmac239, which is up to 100 times more deadly than HIV.
Infected monkeys usually die within two years, but in some inoculated primates the virus did not take hold.
It used the infectious power of CMV to sweep throughout the body. But instead of causing disease, it has been modified to spur the immune system into action to fight off the SIV molecules.
“It maintains an armed force, that patrols all the tissues of the body, all the time, indefinitely,” explained Prof Picker.
The researchers gave rhesus macaque monkeys the vaccine, and then exposed them to SIV.
They found that at first the infection began to establish and spread. But then the monkeys’ bodies started to respond, searching out and destroying all signs of the virus.
Of the monkeys that successfully responded to the vaccine, they were still clear of infection between one-and-a-half and three years later.
Prof Picker said his team was still trying to work out why the vaccination worked in only about half of the monkeys.
“It could be the fact that SIV is so pathogenic that this is the best you are ever going to get.
“There is a battle going on, and half the time the vaccine wins and half the time it doesn’t,” he said.
The researchers are now testing the vaccine to see if it can be used after SIV exposure to treat and potentially cure infected monkeys.
They also want to see if the technique could work in humans.
Prof Picker said: “In order to make a human version we have to make sure it is absolutely safe.
“We have now engineered a CMV virus which generates the same immune response but has been attenuated [modified to lose its virulence] to the point where we think it is unequivocally safe.”
This would first have to pass through the regulatory authorities, but if it does, he said he hoped to start the first clinical trials in humans in the next two years.
Commenting on the research, Dr Andrew Freedman, from Cardiff University School of Medicine, said: “This suggests that prophylactic vaccines – vaccines designed to prevent infection – using CMV vectors may be a promising approach for HIV.
“While they may not prevent the initial infection, they might lead to subsequent clearance, rather than the establishment of chronic infection.”
CHENNAI: The combination of diabetes and tuberculosis doesn’t just complicate treatment ; the double disease could be as dangerous as having HIV/AIDS with TB. A new study has confirmed that diabetes can make the TB bacteria harder to treat, just as HIV/AIDS does.
A group of doctors from MV Hospital for Diabetes, who pored over records of tuberculosis patients registered in the government’s Revised National Tuberculosis Control Programme in Chennai, Tiruvallur and Kancheepuram , found that at least 50% of TB patients had diabetes or pre-diabetes .
All patients were given medication under the DOTS (Directly Observed Treatment Short Course) programme, recommended by World Health Organisation for TB control. At the end of two months, doctors did a sputum test to see if medicines had brought down infection. Nearly 14% of patients with diabetes tested positive for TB compared to 3% of those without diabetes . After six months, doctors said 4% of TBdiabetes patients had not responded to treatment compared to 0.7% of those without diabetes.
The effect of diabetes on TB is similar to HIV on TB, said diabetologist Dr Vijay Vishwanathan , who led the research team. They will urge the government to integrate national programmes for TB and diabetes. “We must ensure that all TB patients are tested for diabetes and vice versa,” he said. According to the Union health ministry, 40% of Indians are TB carriers. At least 10% of people in India are diabetic and in cities like Chennai the incidence is 20%.
“The chances of TB recurrence are higher among diabetics. We are planning a larger study to determine a new treatment regimen, including better diagnosis methods for TB-diabetes patients,” said Dr Vishwanthan.
National Institute for Research in Tuberculosis director Soumya Swaminathan said they did a study among 100 patients with TB and diabetes and found that if sugar levels are under control, treatment outcomes are better. “This hardly happens. TB is diagnosed when patients are in their 40s, the same time when many learn they are diabetics as well,” she said.
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.
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
The district is on the HIV watch list after 6,539 HIV positive patients have gone “missing” and cannot be traced despite a sprawling network of voluntary organisations and heavy fund flow from Government and private agencies.
An alert has been sounded for fear that these missing patients could be silently spreading HIV among the population in and around Madurai.
Not undergoing treatment, these HIV patients remain at large and have dropped out of the surveillance radar.
“Tracking them is a challenge for us and I have already alerted the higher-ups at TANSACS headquarters in Chennai,” said Dr. M. Kalirajan, District Programme Manager, Madurai District AIDS Prevention and Control unit, while presenting the HIV prevalence report on July 2.
Every year, more than 1,000 new cases are added to the ‘positive’ list in the district. From January to December 2012, the data points to 1,048 confirmed HIV cases, while 1,217 persons tested positive in 2011. In 2010, Madurai district had 1,374 HIV positive cases.
Madurai district occupies the fifth place in the overall prevalence of HIV/AIDS in Tamil Nadu, according to the 2011-12 survey, after Salem, Namakkal, Vellore and Chennai.
As per last year’s records, the total number of patients in two categories — HIV positive and those who require Anti Retroviral Therapy (ART) — was 16,225 in Madurai district.
Of these 1,406 died in the last few years, bringing the number down to 10,939. Among these patients, 4,400 positive cases have shifted to other districts.
“Currently 3,880 are on ART and the whereabouts of 6,539 patients have to be established. Wrong address, door locked and transfer were cited as reasons by our field staff,” Dr. Kalirajan said.
Prevention, counselling and treatment activities are carried out through 28 Integrated Counselling and Testing Centres in the district, apart from government hospitals at the taluk level and the Government Rajaji Hospital here. The focus is on high risk groups — female sex workers, homosexuals, transgenders and migrants.
Voluntary organisations such as Pache Trust at K. Pudur have also reported “missing” patients.
“Fearing stigma and discrimination, some are giving us false addresses and that makes it difficult for us to keep track of them,” says G.S. Sujatha, project manager.
A few “hotspots” from where HIV cases are detected in Madurai district are Melur, Karungalagudi, Kottampatti, Alagarkoil, Anaiyur, Alanganallur, Thirumangalam and Usilampatti. The combination of HIV with tuberculosis (358 persons have both as per the latest figures) is proving deadly and there are fears that the general population is at risk when detected patients do not go for follow-up treatment.
Mother-to-child transmission is another major challenge. From 1998 to 2012, the district had 896 HIV positive cases among children in the age group of 2 to 17 years. The whereabouts of 697 children are not known, according to Dr. Kalirajan. Last year, 49 pregnant women tested HIV positive in the district.
The report pointed out that 35 per cent of those (general category) who were detected with HIV are not going for treatment.
Inadequate staff and the lack of job security in the District AIDS Prevention and Control unit, which is situated in the Collectorate here, are cited as reasons for low motivation levels.
“There are only nine employees and all are on contract. We are like bonded labour here, no medical leave and no guarantee of job security. Here, anybody can be shunted out at any time,” laments supervisor K. Nagarajan.
The flip side is many patients living with HIV are leading a normal life thanks to regular medication and motivational counselling.
Kottaichamy (45) of Kottampatti block tested positive 15 years ago and, through the support of an NGO, is managing the immunity level of his body to control infection.
“My wife, myself and my son, who is studying in Class VIII, are all HIV positive. My wife tested positive when she was pregnant,” he admits candidly.
Another affected patient is now living with hope after she was counselled following two suicide attempts. Bhama (name changed), a 32-two-year patient, is now an HIV counsellor in Karungalagudi/Kottampatti area.
“For the past 10 years, I have been living with HIV. I got it through my husband and we are now divorced. I will help all members of the HIV community to lead a normal life,” she says. Bhama has a 11-year-old daughter.