[bridgettpayseur]

For more than twenty five years, researchers have been trying to find a way to stop the spread of the human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS). The virus has proven difficult to stop for many reasons. HIV is a retrovirus. This means it contains a genome composed of RNA, which is then reverse transcribed into DNA once the virus has entered the host cell. Once the DNA has been made, it is integrated into the host cell’s genome. This means that whenever the host cell replicates, the viral genome replicates as well. Once the viral DNA has been inserted into the genome, the host cell’s transcription and translation machinery will produce viral proteins, reproducing the virus. The newly formed viral particles will then leave the host cell, without killing it, to infect new cells.

A clinical trial of an HIV vaccine which began in 2009 was recently stopped. Twenty five hundred participants in the trial received either a placebo injection, or an experimental HIV vaccine. A safety review recently showed that slightly more patients who received the vaccine were infected with HIV than patients who received the placebo. In addition, patients who received the vaccine did not have lower viral loads compared to patients who received the placebo.

The vaccine being studied was based on an adenoviral vector. Adenovirus is a cause of the common cold, and has been studied in bioengineering as a vector for vaccination and gene therapy treatments. The adenovirus was engineered to produce HIV proteins, and then train CD8+ T cells to recognize virus infected cells and destroy them. The study used a prime-boost strategy, in which volunteers were given two doses of the vaccine to prime the immune system, and then produce a stronger, secondary immune response. While the failure of the study is disappointing, it is not entirely unexpected. Over the past twenty five years, there have been HIV vaccine trials. A recent study in Thailand showed some promise, but the study needs to be expanded on to find a more effective regimen. Other HIV vaccine trials have not been as successful. Indeed, many previous trials have been halted due to poor performance of the vaccine.

There are many reasons why it has been so difficult for scientists to produce a functional HIV vaccine. A strong CD4+ T cell response early during HIV infection has been shown to enhance the pathogenicity of the virus, resulting in increased viral load and more severe disease. CD8+ T cells are a popular target of vaccine design, as they are able to directly recognize and kill virus infected cells. However, because HIV is a retrovirus, it is highly susceptible to mutations. These mutations occur from high error rate of the reverse transcriptase protein. The mutations may alter the viral proteins enough that they are not recognized by the CD8+ T cells, and can escape the immune response. In fact, the mutation rate of HIV is so high, that many patients are infected with many different subspecies of virus. In addition, there are many different strains and subtypes of HIV, and a vaccine specific to one strain may not elicit an immune response against other strains. Lastly, because many HIV vaccines currently in development utilize live vectors, such as a virus or bacteria, it is possible that a patient might already have encountered that vector, and have an immune response against it. If this happens, the patient’s immune system would destroy the vector before it has a chance to induce an effective anti-HIV immune response.

Currently, research indicates that the production of broadly neutralizing antibodies may be the best route to take when exploring potential HIV vaccines. Broadly neutralizing antibodies have been found in some long term non-progressors, which are patients who have been infected with the virus but have been able to maintain low to undetectable viral loads without antiretroviral therapy. The broadly neutralizing antibodies recognize portions of protein that are highly conserved throughout many HIV strains. Because these proteins are important for viral binding and entry into the host cell, they do not mutate at a high rate, either. Scientists are studying ways to induce production of these broadly neutralizing antibodies in hopes of providing protection against a large range of HIV strains and subtypes. In the end, a combination of broadly neutralizing antibodies, along with strong CD8+ T cell responses, will probably be the most effective method for preventing, or at least controlling, HIV infection with a vaccine.


References:

http://www.cbsnews.com/8301-204_162-5758...nfections/

http://www.dailymail.co.uk/health/articl...paign=1490

[lyka_candelario]

This particular study is actually intriguing. Here’s how I partially summarized it:

HVTN means HIV Vaccine Trial Network. This was a study conducted in 2009 as an exploratory clinical trial to investigate the HIV Vaccine regimen. The National Institute of Allergy and Infectious Diseases (NIAID) conducted the trial.

It had several goals which were to test if the vaccine regimen:
a. could lower the amount of viral load or blood HIV of people who were later infected with the virus, but vaccinated beforehand;
b. was safe, as previous trials showed to be so;
c. could prevent HIV infection;
d. had similar results compared to the RIV 144 HIV Vaccine trial in Thailand; and
e. had promising effects to the monkey equivalent HIV infection.

The trial was halted after an independent data and safety monitoring board (DSMB) discovered on April 22, 2013 that it did not lower viral load among recipients who were later infected and did not prevent the occurrence of HIV infection.

Interestingly, the regimen actually had two kinds of vaccines administered. One is to prime the immune system, while the other was designed to boost such. This, in turn, makes the body produce several types of immune responses when compared with other vaccine regimens using only one type.

For eight weeks, there will be three immunizations given. Not only that, a weakened adenovirus type 5 (Ad5) is administered as a recombinant boosting vaccine to further stimulate the immune system. Such viruses are the cause of common colds, but both the Ad5 and the HIV immunizations, for years, have been proven not to cause an infection.

The HIV particles used for the immunizations are not made from a weakened (attenuated), live, or killed virus. They are only pieces of the virus, but are lacking enough to cause AIDS.

The study team had 2,504 HIV-negative male enrollees who were circumcised, had no antibodies to the Ad5 virus, and have had sexual contact with men. Their ages were between 18-50 years old and all of them resided in the United States.

For more info, you may go directly to their website:
http://www.niaid.nih.gov/news/QA/Pages/H...a2013.aspx