Fighting HIV Without Traditional Vaccines

Why can't scientists just develop a universal vaccine against HIV and the swine flu? Is it because the biopharm industry wants to make money each year off of a new vaccine?

The answer to the second question is a definite "no", but the answer to the first question is far more complicated....

The problem is that HIV, and in fact many viruses, do not play fair. Viruses, although not technically "alive", evolve over time. One way that viruses evolve is by changing the protein structure of their outer protein coat. This protein coat is responsible for the majority of the properties of a virus - for example what species and types of cell in infects. In viruses, the evolutionary rate of change is higher than that of living organisms, for several reasons, including the fact that viruses lack DNA repair mechanisms. This means that they accumulate mutations faster, and often these mutations change the outer structure of the virus. Since vaccines are prepared using purified outer proteins of a virus, you can see how as viruses evolve they make previous vaccines ineffective. Such is often the case in the flu vaccine, where the yearly vaccines are prepared from the previous year's flu viruses. Vaccines for HIV has so far met limited success, and epidemiologists balk at the idea of putting a vaccine on the market which would make people think that they are safe. Furthermore, HIV belongs to a class of viruses called the retroviruses, an especially nasty sub-set of viruses that accumulate mutations faster than most.

Vaccines, when introduced into the body, cause the immune system to target specific cells and proteins for destruction. This is called the specific immune response, and one of the ways that it works is to produce antibodies against the invading virus. Unfortunately, we all do not generate the same antibodies, meaning that a vaccine in one person might not have the same result as in another. Coupled with the high mutation rates of viruses, this causes real problems in developing a population-wide vaccine for highly mutable viruses.

But what if we could bypass the whole antibody-generation step and instead introduce virus-specific antibodies into the body. These antibodies could be designed to target a specific type of virus, and would actively recruit the cells of our immune system to destroy the virus before it caused significant damage. This type of procedure has just been reported for HIV-type infections in primates, and the initial results suggest that it might hold promise. And not only for HIV, but also for viruses such as H1H1 (swine flu) and H5N1 (avian flu). Both of these are now in the human population, and the development of an effective vaccine against them both is not soon forthcoming, so adding a new technique to our anti-viral arsenal is well advised.


For more information - see Jon Cohen's article in ScienceNow
"Designer Antibodies Derail Monkey AIDS Virus"

The Swine Flu "Pandemic"

Welcome to the new world of medical sensationalism. The recent "outbreak" of the H1N1 virus, aka "swine flu" has provided some of the major news networks with the ultimate story. Scare the public and increase ratings, it worked with terrorism, and now it appears to be working with the swine flu pandemic. From pictures of Dr. Gupta, CNN's medical authority, wearing a worried look and a face mask, to Vice-President Biden's gaff about why all Americans should cease flying immediately, the American people are being fed misinformation on H1N1 at an alarming rate. And they are scared. Airline stocks are plummeting, people are avoiding pork, and sales of surgical masks are increasing exponentially. In Vermont, the National Gaurd is escorting deliveries of anti-viral medicines to hospitals. And, of course, the religious crazies are out predicting the "end of days".

Every day we are reminded of the swine flu death toll. For example, on today's CNN page (May 3, 2009), there is a headline article stating that "Confirmed Cases of H1N1 Virus Approach 900". It is important to realize that 900 deaths, while seemingly significant, really is not. Cancer kills over 440,000 Americans per year, or about 1200 a day. Over 9000 Americans, 24 each day, die from contaminants in the food that we eat. In fact, 900 deaths worldwide represents about 0.00013% of the world's population. This is a nasty little virus, with some interesting genetics (see tomorrow's post!), but it is not yet a global killer. And due to some rather quick work by scientists, we already know more about this virus than most.

So why the panic? Mostly because people do not understand the jargon of the people who study infectious diseases. Yes, there is a pandemic... but it is important to recognize what the word pandemic really means. An epidemic is an outbreak of a disease in a localized population, while a pandemic simply means that the epidemic has moved into neighboring populations. In today's world, most epidemics, and all flu outbreaks, go pandemic quickly. A pandemic is not Armageddon, it is simply a widespread outbreak of a disease.

Some people will say that the news networks are just keeping people informed. But the reality is that this bout of swine flu is going to fade rather quickly as summer progresses, and with this fading will be the attention of the American people. But, unfortunately, the virus will be back, and it could return with a vengeance. But due to the actions of the news networks, we are now in the "boy who cried wolf" syndrome. When this virus, or one of its close relatives returns, most people will ignore the advice to get a vaccine, thinking that this is just another "news story", and not a real threat. After all, they have already survived the "threats" from avian and swine flu, how bad can it get? The answer is, very bad indeed. Viruses are patient little objects, and a few seasons of low activity often preclude a true outbreak in a population. H1N1 may not be bad this year, but if it mutates over the summer, we could have problems next year if we don't prepare now by planning ahead and funding the agencies that work to protect us from infectious outbreaks.

For more, quality, information, stop watching the infomercials known as the nightly news, and check out real sources such as the CDC. Take prudent precautions, the same as you would take during any high-disease season. Wash your hands frequently, especially when you have been in public spaces, and see your doctor if you develop flu-like symptoms. But lets stop the panic and sensationalism, and instead use our brains to think.

Advances in Cancer.... Linking the Pieces

As part of the Darwin Bicentennial Lecture Series at Appalachian State University, Dr. Paul Ewald, author of Plague Time: The New Germ Theory of Disease, recently gave a presentation on the genetic basis of cancer. During the lecture, Dr Ewald spent a considerable amount of time discussing the role of infectious agents, specifically viruses, as the causative agents of cancer. Specifically, Dr Ewald talked about the human papillomavirus (HPV), and how screening of seemingly unrelated cancers, such as breast cancer and cancers of the head and neck, are linking this virus as a potentially more important agent in cancer formation than previously thought.

If infectious agents are responsible for priming cells to enter into a tumor-forming stage, as Dr Ewald's work strongly suggests, then the use of vaccines against these agents could be a major advance in the evolution of preventative strategies against cancer. HPV vaccines are already recommended for young women to prevent against cervical cancer later in life. Now it appears that these vaccines may have potential benefits in other areas as well.

Interestingly, a recent article in Science Daily (Genetic Markers for Aggressive Head and Neck Cancers) presents data from a study at the Albert Einstein College of Medicine that a specific type of genetic markers, called microRNAs, may be used to identify individuals who are highly susceptible to forms of head and neck cancer. The researchers in this study propose that genetic screening may be useful in the development of new treatments for these cancers.

Is is possible that the microRNA markers identified by the team at the Albert Einstein College of Medicine are actually indicating susceptibility to the HPV virus? We know that everyone who carries HPV does not necessarily develop cancer, but the reason why is not yet clear. It could be that a genetic susceptibility is the key. Certain genetic combinations could promote HPV influence, and result in the formation of the cancer phenotype. If this is the case, then trials of using the HPV vaccine on individuals who have these specific microRNA markers are definitely in order. This could provide some very useful insights on new treatments of specific types of cancers, specifically those that have been identified to be associated with an infectious agent.

The Death of Junk DNA and Birth of the Junkome

Not so long ago, geneticists considered the vast stretches of non-coding regions in DNA to be “junk,” nothing more than the remnants of our evolutionary history. If it wasn’t a traditional gene, and didn’t produce a protein, it wasn’t of interest to most scientists. Luckily, not everyone considered these regions of DNA to be junk. Some considered the junk DNA to be the dark matter of the genome. They believed that it must have some function, but no one had yet determined exactly what that function was.

One of these individuals is Dr Craig Pikaard at Washington University- St Louis. His research group has discovered another use of junk DNA – it acts as a component of the cellular immune system by enhancing the ability of the cell to combat infection by viruses and transposons (also known as “jumping genes”). In a recent manuscript published in the journal Cell (vol 135 #4) Pikaard and associates demonstrate that in Arabidopsis , the fruit fly of plant genetics, the RNA polymerases within the cell use these non-coding regions of DNA to silence viruses and transposons. RNA polymerases are normally active in the process of transcription – the first stage of gene expression. Pikaard’s work suggests that these regions of “junk” DNA may be important in the generation of small interfering RNAs, so siRNAs. siRNAs are known to be involved in the silencing of genes by interfering with the transcription process. The medical community is very interested in the use of siRNAs in the prevention and treatment of diseases. Pikaard’s discovery in Arabidopsis should pave the way for additional studies in animals.

It seems that the time has come to let the term “junk DNA” fade into obscurity. In its place lets use the term “junkome” – those regions of DNA that we have no idea what they do, but agree that they must do something. After all, assuming something does not have a function because we do not understand what it does is not a lesson that we should be teaching young scientists.

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WUSTL news release

Dr Google

Is there anything that Google can't do?

An article in the NY Times ("Google Uses Searches to Track Flu's Spread") by Miguel Helft reports that Google may be able to detect outbreaks of influenza up to two weeks earlier than the Centers for Disease Control (CDC). According to Google, people who have the symptoms of the flu search for terms such as muscle aches and flu on the search engine, and data-mining of these searches can help pinpoint outbreaks in advance.

There are several alarming items that can be derived from this report.

• Google is faster at reporting medical events, epecially outbreaks, than the CDC. Maybe we should not be suprised by this since the CDC is a government agency, but one has to wonder what is in this for Google. After all, Google is a for-profit (and big profits!) business, and we may want to be careful about turning over reporting to a private company.
• People search the internet before seeing their doctors. We all knew that this was the case, and we have all done it. Who wants to sit in a doctor's office for 3-4 hours when they are sick? But this also means that people are using Google as their primary first source of medical information. Anyone who lives on the web knows the amount of garbage that exists in cyberspace.
  

There is also some good news from this study.

• We all know that the government is not known for its ability to respond rapidly. The use of the studies by both Google and Yahoo! may help develop a more rapid response plan. Maybe we don't need it for influenza, but other outbreaks, such as SARS and Avian flu, may require a faster response time than the CDC can currently supply.
  

What would be interesting is if Google informed the medical community on where these people were going to get their information on the web. Is it a reliable source, such as WebMD, or is it Bob's Influenza Shop? Maybe then the medical community can start to use the web effectively to deliver useful information to the public.

The Battle Against Viruses Heats Up

Viruses are nasty opponents, as anyone who has followed the battles against influenza, SARs and HIV/AIDS can attest. They are diverse and in many cases evolve at rates that confound efforts to contain them. Anyone who has gotten a flu shot, and then came down with the flu a few months later because the “strain” of virus that the vaccine was not the same as the “strain” that they were infected with, knows just how fast viruses can evolve. In many cases, medical professional never really know which virus has caused the symptoms in their patients, and this complicates treatment and often leads to the misuse of antibiotics, which, of course, are never effective against viruses.

At the ScienceWriters 2008 New Horizons in Science meeting at Stanford University (sponsored by CASW) this week, Dr. Joseph DeRisi of UCSF presented an interesting talk on his research to develop a new form of “chip” as a diagnostic tool for identifying the viral contributions to diseases. Gene chips are often used by molecular biologists to determine the relationship between a gene and an observed condition. Dr DeRisi's work takes this approach one step further.

What is interesting here is Dr. DeRisi’s application of evolutionary genomics to his work. Like microbiologists, virologists recognize that they have only identified a small fraction of the diversity of viruses that are out there in the natural world. Despite advances in sequencing technology, the ability to sequence every virus in a given environment, such as a fecal or nasal sample, is still not cost effective. However, what Dr DeRisi has done is to develop a “viral chip” that contains not the entire sequences of every virus, but rather the sequences of key genes that are evolutionarily important to certain families of viruses. When one of these viral chips is exposed to a sample, a computer program determines the level of similarity between the DNA (or RNA) in a virus and the sequence on the chip. For previously unknown viruses, this can allow a quick classification of the virus to a certain group, and has been proven to be very successful by Dr. DeRisi’s team in diagnosing diseases for which no known cause could be determined by diagnostic tools.

Furthermore, Dr DeRisi has proposed making these chips available at cost to the medical community through a non-profit organization. The availability of a new technology at an inexpensive cost would represent an important new development in the war against viruses, and would rapidly generate an increase in data for public health officials.

Additional Links

DeRisi Lab at UCSF