David Borradale – Australian Science

Hopeful results in latest HIV vaccine trial, but many hurdles to overcome yet

David Borradale — Mon, 23 Sep 2013 00:24:51 +0000

A HIV vaccine, known as SAV001-H has shown promising results in an early clinical trial, with no adverse effects reported and importantly, a significant increase reported in HIV specific antibodies in participants who received the vaccine. In this trial, 33 HIV positive participants were randomly allocated to one of two groups: half into a treatment group receiving the vaccine and half into a placebo group who did not receive the vaccine. The participants were followed up at regular periods, testing safety of the vaccine and antibody response over a one year period. The vaccine has been developed by Dr C. Yong Chan and his team at the University of Western Ontario and has been licensed for commercialisation by the biotechology company Sumagen.

This is welcome news for a disease which killed an estimated 1.7 million people in 2011 (WHO, 2013). Furthermore, there are an estimated 34 million people around the world living with HIV/AIDS, and the disease continues to have a devastating impact in Sub-Saharan Africa where up to a quarter of the population in countries such as Botswana, Lesotho and Swaziland are infected (WHO 2013; UNAIDS 2013). While great strides in treatment of HIV; via the development of antiretroviral (ART) medications, have been made by extending the time it takes for HIV to develop to AIDS, ART treatment is not yet available to all, particularly in the poorest nations; and of course, treatment is much less optimal then prevention of HIV in the first place.

Worldwide adult HIV Prevalence (Click for larger)

The long road to effective HIV vaccines

However development of successful HIV vaccines has proven to be highly elusive, due in part to the rapid mutation rate of HIV, these mutations generating a diverse population of quasi-species of HIV over the length of the infection period – the immune system, itself the target of HIV, is simply not able to keep up (Ackerman and Alter, 2013). This immense genetic diversity of HIV has meant that targeting HIV with effective, universal vaccines has been particularly difficult.

This leads to a cautionary note that must be taken regarding SAV001-H; this was a small, very early trial of this particular HIV vaccine. These early trials are referred to as Phase 1 trials, meaning that its primary focus was on assessing the safety of vaccine, with efficacy or effectiveness assessed only as a secondary objective (see graphic, below). Phase 2 and 3 trials are planned next and it is these trials which are particularly focused on assessing the effectiveness of the vaccine to prevent HIV infection in large numbers of HIV negative participants at high risk of contracting HIV. Furthermore, other promising HIV vaccines have passed through early Phase 1 trials, only to show in later trials no significant efficacy. An example of this was a highly anticipated STEP trial, which was a large Phase 2 trial enrolling 3,000 high risk individuals randomised into a vaccine or placebo group. The vector based vaccine used in this trial failed to show any effect on reducing risk of infection and indeed those receiving the vaccine appeared to be at greater risk of contracting HIV (HTNV, 2013).

Clinical trial phases

Thus some of the early media reports for SAV001-H which have been mentioning ‘eradication’ are very premature and paying scant heed to the long (and sometimes disappointing) road that this vaccine must pass through with its coming Phase 2 and 3 trials, as demonstrated above with the example of the STEP HIV vaccine trial. These promising early results from this latest HIV vaccine trial must be tempered by the historical difficulties in conducting successful HIV vaccine trials.

Cautious optimism

Despite the very real need for caution at this early stage, there are several reasons why many in the health community are particularly optimistic about SAV001-H. This optimism is largely due to the fact that SAV001-H takes a new approach to HIV vaccine design as it uses whole killed HIV viruses. Previous HIV vaccine strategies have used other strategies such as subunit vaccines which basically introduce important proteins (called antigens) to the body to induce a specific immune response, or vector based vaccines to introduce genetic material from the HIV virus via another ‘carrier’ virus; both approaches proving disappointing so far (Sumagen, 2013).

HIV structure: gp120 and gp41 are essential in fusion to immune cells and subsequent invasion

For SAV001-H, the HIV-1 virus is genetically engineered by deleting the activity of specific genes involved in the disease causing process (pathogenicity) and then chemically treated and bombarded with gamma radiation to disable its ability to multiply within human cells (virulence) (Sumagen, 2013). This way, the immune system will still detect and mount a response against the invading virus, but the virus is no longer able to cause disease. The early data from the Phase 1 trial are particularly encouraging as it has been reported that vaccination with SAV001-H produced large increases in two particular antibodies specific for the p24 envelop antigen and gp120 surface antigens of HIV-1 (Western News, 2013).

While gaining plenty of attention, SAV001-H is only one of multiple vaccines in development; a major focus of several other research efforts, are vaccines designed to induce potent antibodies, known as broadly neutralizing antibodies (bNAbs), that are able to potentially block HIV infection (Korber and Gnanakaran, 2011). Promising early research into vaccines that may be able to effectively induce these bNAbs and provide effective immunity against HIV infection have provided another boost to HIV vaccine development efforts. So there is certainly reason to be hopeful about SAV001-H, but we need to mix this hope with a healthy dose of caution at this stage. Also, it is worth noting that any effective HIV vaccines will likely be just one, albeit very important, part in a multitude of preventative strategies, including sex education, male circumcision, microbiocide gels and prophylactic antiretroviral therapies which will result in the effective prevention of HIV infections worldwide.

Sources:

1. World Health Organisation. HIV Data and Statistics [Online]. Available at: http://www.who.int/hiv/data/en/

2. United Nations AIDS (UNAIDS). AIDS Information by country [Online]. Available at: http://www.unaids.org/en/dataanalysis/datatools/aidsinfo/

3. Ackerman M, Alter G. 2013. Mapping the Journey to an HIV Vaccine. NEJM 369(4): 389-391.

4. HIV Vaccine Trials Network (HVTN) [Online]. Available at: http://www.hvtn.org/science/step_buch.html

5. Sumagen. AIDS vaccine [Online]. Available at: http://www.sumagen.co.kr/english/business/aids_vaccine.htm

6. HIV vaccine produces no adverse effects in trials. Western News, September 3, 2013 [Online]. Available at: http://communications.uwo.ca/western_news/stories/2013/September/hiv_vaccine_produces_no_adverse_effects_in_trials.html

7. Korber B, Gnanakaran S. 2011. Converging on an HIV Vaccine. Science 333; 1589-1590.

All images sourced from public domain (Wikimedia)

Cite this article:
Borradale D (2013-09-23 00:24:51). Hopeful results in latest HIV vaccine trial, but many hurdles to overcome yet. Australian Science. Retrieved: May 02, 2024, from http://australianscience.com.au/health/hopeful-results-in-latest-hiv-vaccine-trial-but-many-hurdles-to-overcome-yet-3/

test

The post Hopeful results in latest HIV vaccine trial, but many hurdles to overcome yet appeared first on Australian Science.

Combating the rise of the superbugs: The health and scientific challenges of antibiotic resistance

David Borradale — Thu, 14 Mar 2013 00:01:17 +0000

It’s hard to imagine the world prior to antibiotics, a world where even a deep laceration could frequently spell significant illness or even death due to infection. Thankfully, since the discovery of penicillin in 1929 by Alexander Fleming, we now have a range of potent antibiotics to treat many of the various types of bacterial infection.

There is a problem though, bacteria are great survivors and have been competing against other bacteria and microorganisms for billions of years. As Professor Matt Cooper from the University of Queensland puts it “Billions of years ago, bacterial species were engaged in an arms race against each other and the chemicals they developed to kill one another have been modified into today’s antibiotics”.¹

Multi-Drug resistant Tuberculosis is a particular concern for health authorities and clinicians due to limited treatment options.

Unfortunately it’s our overuse of these important drugs which has driven the rapid development of antibiotic resistance, the process whereby bacteria containing mutations in their DNA, that provide some protection from an antibiotic, have an enormous survival advantage when exposed to the antibiotic and pretty soon dominate. Frequent exposures to the antibiotic may further strengthen these survival traits via the selection process, rendering the the drug less effective over time. It’s a great example of random variations leading to non-random adaptions through natural selection, although one with profound consequences for human health.

Of particular concern are bacteria that have developed resistance to multiple types of antibiotics, resulting in particularly dangerous resistant bacteria such as the multi-drug resistant variants of tuberculosis, that are extremely difficult to treat. Indeed leading health authorities are so worried about the problem that the Chief Medical Officer of the UK, Professor Dame Sally Davies, has recently labelled the threat as “catastrophic

Cite this article:
Borradale D (2013-03-14 00:01:17). Combating the rise of the superbugs: The health and scientific challenges of antibiotic resistance. Australian Science. Retrieved: May 02, 2024, from http://australianscience.com.au/biology/combating-the-rise-of-the-superbugs-the-health-and-scientific-challenges-of-antibiotic-resistance/

test

The post Combating the rise of the superbugs: The health and scientific challenges of antibiotic resistance appeared first on Australian Science.

Science or fringe science? Removing the ‘giggle factor’ from Near Earth Object impacts

David Borradale — Wed, 12 Sep 2012 00:50:17 +0000

On June 30, 7.17am in a remote, sparsely inhabited area in Siberia, Russia, near the Podkamennaya Tunguska River, occurred an event of enormous devastation. An asteroid or comet estimated to be 40-50 meters in diameter, exploded at low altitude with an energy almost 200 times that of the atom bomb dropped on Hiroshima. Trees where knocked down over an area of two thousand square kilometres, hundreds of reindeer where killed and the seismic shock from the airborne explosion was registered on barometers in England. Eyewitnesses 60km away, reported seeing the northern sky covered with fire, followed by an enormous bang, though thankfully no human deaths were recorded.

Fallen trees at the Tunguska impact site

Dan Yeoman from NASA’s Jet Propulsion Laboratory stated in an interview in 2008, “the Tunguska event is of great importance not only because of the devastation caused to a thankfully remote area, but also as it is the only modern era event of this type where we actually have first-hand accounts.

test

The post Science or fringe science? Removing the ‘giggle factor’ from Near Earth Object impacts appeared first on Australian Science.

An outdated appetite control system in a rapidly evolving world?

David Borradale — Tue, 07 Aug 2012 03:54:08 +0000

Imagine yourself for a moment waiting for a meal at your favourite restaurant, local takeaway store or at home counting down the time until the oven buzzer sounds. You know you’re hungry, but we seldom think or care about the complex series of processes that go on inside our bodies that drive that hunger.

And why should we care?

In the developed world, for the lucky majority at least, calorie-dense food has never been more accessible. Want a pizza? Just use an app from your smartphone to order one delivered any time, day or night. The one big problem with this–human appetite has evolved over tens of thousands of years when food was tough to come by, and we had to work physically hard for a meal, now we just go to the fridge. However the series of long developed processes that drive appetite have not caught up in this time of plenty thereby contributing to the modern day upsurge in obesity.

Obesity as a global problem

Obesity is a global disease on the increase, the World Health Organisation estimates that by 2015 there will be an astounding 700 million adults classified as obese. From a health viewpoint this is particularly worrying as obesity is a major risk factor for cardiovascular diseases, Type-2 diabetes and some cancers.

Also concerning, is the number of people in developing countries at risk, where the bane of obesity joins established under-nutrition. Dr Ranjan Yajnik, the director of the diabetes unit at King Edward Memorial Hospital in Pune, was recently reported by ABC News saying, “Populations which have faced under-nutrition for a long time are now exposed to the over-nutrition of the modern world through globalisation and westernisation”.

In short, it’s the modern world and how we live in it which is driving up rates of obesity.

An unbalanced system?

In broad terms, the body is wired to protect against starvation and low food availability, by increasing biological and sensory processes that promote the need to eat. This makes sense, after all starvation is an immediate threat to survival and was by far one of the greatest concerns of our ancient ancestors. As excessive food was less of a concern, the regulatory processes to protect against excess consumption and weight gain appear less effective, leading to the body favouring weight gain over weight loss.
Combine this with the increased availability of highly palatable foods, and the ability to stop eating when full is increasingly difficult. According to Dr. Joanne Harrold and colleagues, in a recent paper published in the journal Neoropharmacology, this may be especially true for many obese people, who may “possess an over-responsiveness to the reward effects of eating, which results in the appetite system of these people being effectively overwhelmed

test

The post An outdated appetite control system in a rapidly evolving world? appeared first on Australian Science.