Expansion of HIV/AIDS Vaccine Program Announced by GeoVax Labs, Inc.

/PRNewswire/ -- GeoVax Labs, Inc. (OTCQB/OTCBB: GOVX), announced today that it is expanding its preventative HIV/AIDS vaccine development effort in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health (NIH) and the HIV Vaccine Trials Network (HVTN). Specifically, the HVTN plans to clinically test a novel vaccine product developed by GeoVax scientists that expresses human granulocyte-macrophage colony stimulating factor (GM-CSF) in combination with inactivated HIV proteins. The novel vaccine consists of a recombinant DNA vaccine co-expressing human GM-CSF and non-infectious HIV virus-like-particles. The DNA vaccine is used to prime immune responses that are subsequently boosted by vaccination with a recombinant modified vaccinia Ankara (MVA) vectored vaccine. The MVA expresses the HIV virus-like-particles, but does not express GM-CSF. The regimen builds on the GeoVax DNA/MVA vaccine that is currently in Phase 2a clinical testing through the HVTN.

GM-CSF is a cytokine (growth stimulating protein) that serves to expand and mature cells that initiate immune responses and has undergone extensive testing in humans for cancer vaccines. The GM-CSF-adjuvanted vaccine was added to GeoVax's portfolio because of the outstanding ability of the simian prototype vaccine to induce immune responses that prevented simian immunodeficiency virus (SIV) infection. In nonhuman primates, the GM-CSF enhanced vaccine achieved protection against SIV in 70% of the animals. Protection was measured against 12 weekly rectal challenges using a dose of SIV which is estimated to be 30 to 300 times higher than the typical exposure dose of HIV in mucosal transmission in humans.

"For years, the HIV vaccine field has been working with vaccines that elicited immune responses that primarily controlled immunodeficiency virus challenges in infected animals, but did not actually prevent infections. The ultimate goal is to prevent infections. The co-expression of GM-CSF with the SIV proteins is a vaccine design that appears to be a large step towards reaching this goal," said Dr. Harriet Robinson, Chief Scientific Officer at GeoVax. "In our trials in nonhuman primates, GM-CSF enhanced the quality of the SIV-specific antibody response. Antibody is present in blood and tissues and has the potential of blocking SIV before it infects cells. The GM-CSF-adjuvanted vaccine induced the production of antibodies characterized with increased tightness of antibody binding. The tightness of antibody binding, known as avidity, can be expressed as an index. Animals with indices above 40 were protected from infection, whereas animals with lower indices were infected with the number of challenges to infection correlating with their index."

"We are very pleased that the HVTN will be conducting trial HVTN 094 of our GM-CSF adjuvanted vaccine product, which we expect will begin late this year," said Dr. Robert McNally, CEO of GeoVax. "The HVTN, funded by the NIAID, is the largest worldwide clinical trials network dedicated to the development and testing of HIV/AIDS vaccines. We are looking forward to working with an excellent team of HVTN trial investigators."

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NIH Awards $10 Million to Develop Microneedle Vaccine Patch

The National Institutes of Health (NIH) has awarded $10 million to the Georgia Institute of Technology, Emory University and PATH, a Seattle-based nonprofit organization, to advance a technology for the painless, self-administration of flu vaccine using patches containing tiny microneedles that dissolve into the skin.

The five-year grant will be used to address key technical issues and advance the microneedle patch through a Phase I clinical trial. The grant will also be used to compare the effectiveness of traditional intramuscular injection of flu vaccine against administration of vaccine into the skin using microneedle patches. In animals, vaccination with dissolving microneedles has been shown to provide immunization better than vaccination with hypodermic needles.

"We believe that this technology will increase the number of people being vaccinated, especially among the most susceptible populations of children and the elderly," said Mark Prausnitz, a professor in the Georgia Tech School of Chemical and Biomolecular Engineering, and the project's principal investigator. "If we can make it easier for people to be vaccinated and improve the effectiveness of the vaccine, we could significantly reduce the number of deaths caused every year by influenza."

Vaccine-delivery patches contain hundreds of micron-scale needles so small that they penetrate only the outer layers of skin. Their small size would allow vaccines to be administered without pain -- and could allow people to apply the patches themselves without visiting medical facilities.

While the ability to immunize large numbers of people without using trained medical personnel is a key advantage for the microneedle patch, the researchers have learned that administering the vaccine through the skin creates a different kind of immune response -- one that may protect vaccine recipients better.

"We have seen evidence that the vaccine works even better when administered to the skin because of the plethora of antigen presenting cells which reside there," said Ioanna Skountzou, co-principal investigator for the project and an assistant professor in Emory University's Department of Microbiology and Immunology. "This study will allow us to determine how we can optimize the vaccine to take advantage of those cells that are important in generating the body's immune response."

Among the issues to be addressed in the five-year study are:

• Developing an administration system that will be simple to use, intuitive and reliable. "Our goal is to make these patches suitable for self-administration, so that anybody could take a patch out of an envelope, put it on, and have it work with high reliability," Prausnitz said.

• Studying the long-term stability of vaccine used in the patches, and optimizing technology for incorporating it into the dissolving microneedles. "We need to put the vaccine into a dry form in this patch," said Prausnitz. "That will require different processing than is normally done with vaccines. We expect that this dry vaccine will provide enough stability that the patches can be stored without refrigeration."

• Evaluating the economic, regulatory, social and medical implications of a self-administered vaccine. PATH, an international nonprofit organization, will assist with this work, and will help strategically address any issues. "We will be assessing the barriers that may exist to introduction of a self-administered flu vaccine so we can anticipate those issues and develop possible solutions," said Darin Zehrung, leader of the vaccine delivery technologies group at PATH.

The funding will come from the Quantum program of the National Institute of Biomedical Imaging and Bioengineering (NBIB), which is part of the NIH. The initiative is designed to bring new medical technologies into clinical use.

While the funding focuses specifically on influenza vaccination, the lessons learned may advance other microneedle applications -- including vaccination efforts in developing countries where skilled medical personnel are limited and concerns about re-use of hypodermic needles are significant.

Additional design and development of the microneedle patch will largely be done at Georgia Tech, with vaccine development, immunological studies and the Phase I trial carried out at Emory University. The trial, to be conducted by the Hope Clinic of the Emory Vaccine Center, is expected to take place during the final year of the grant, setting the stage for Phase II and Phase III clinical trials that would be required to obtain FDA approval.

Ultimately, the goal will be to produce an influenza vaccine delivery patch that could be made widely available. Prausnitz expects that will be done by an established company with the ability to manufacture and market the devices.

Microneedle drug and vaccine delivery systems have been under development at Georgia Tech and elsewhere since the 1990s. The technology got a significant boost in July of 2010 with publication of a study in Nature Medicine that showed mice vaccinated with dissolving microneedles were protected against influenza at least as well as mice immunized through traditional hypodermic needle injections.

The patches used in that study contained needles just 650 microns long, assembled into arrays of 100 needles. Pressed into the skin, the needles quickly dissolved into bodily fluids thanks to their hydrophilic polymer material, carrying the vaccine with them and leaving only a water-soluble backing. In contrast, use of hypodermic needles leaves the problem of "sharps" disposal.

Prausnitz hopes that the $10 million in NIH funding will help accelerate development of the microneedle patches to make them available for general use within five to ten years.

"This research will focus on optimizing the microneedle-based delivery of vaccines into the skin and understanding how this method affects immune responses both at the mucosal surfaces of the body and through the systemic response inside the body," added Skountzou. "Combined with the convenience of self-administration, painless application and absence of sharps waste, this novel immunization route could make the microneedle patch a powerful new weapon against infectious diseases."

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Statement by Dr. Anthony Fauci, NIH Regarding Early Results from Clinical Trials of 2009 H1N1 Influenza Vaccines in Healthy Adults

Statement by Dr. Anthony Fauci
Director, National Institute of Allergy and Infections Diseases, NIH
Regarding Early Results from Clinical Trials of 2009 H1N1 Influenza
Vaccines in Healthy Adults

We are encouraged by reports that are now emerging from various clinical trials of 2009 H1N1 influenza vaccines, conducted by various vaccine manufacturers. We expect additional companies to announce their preliminary trial results shortly. The early data from these trials
indicate that 2009 H1N1 influenza vaccines are well tolerated and induce a strong immune response in most healthy adults when administered in a single unadjuvanted 15-microgram dose. We congratulate the companies on these trials, which are an important part of the ongoing worldwide effort to develop vaccines to protect the public from 2009 H1N1 influenza.

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, also is conducting clinical trials of 2009 H1N1 influenza vaccines, produced by Sanofi Pasteur and CSL Limited. The NIAID trials are testing two different dosages (15 micrograms versus 30 micrograms) and evaluating the immune response to one and two doses of these vaccines. More than 2,800 people are participating in ongoing NIAID trials of these vaccines.

We are pleased to note that preliminary analyses of early data from the NIAID trials align with the recently announced findings and those to be announced imminently by other companies in that both vaccines studied induced what is likely to be a protective immune response in most adults following a single dose in the same amount (15 micrograms) used in seasonal flu vaccines. Specifically, in blood samples obtained 8 to 10 days after vaccination:

* Among healthy adults who received a single 15-microgram dose of
the Sanofi Pasteur vaccine, a robust immune response was measured in 96
percent of adults aged 18 to 64 and in 56 percent of adults aged 65 and
older.
* Similarly, among healthy adults who received a single
15-microgram dose of the CSL Limited vaccine, a robust immune response
was measured in 80 percent of adults aged 18 to 64 and in 60 percent of
adults aged 65 and older.

Additional data from the NIAID trials are forthcoming. However, on the basis of these strong early data, our results are consonant with other reports that a single 15-microgram dose of unadjuvanted 2009 H1N1 influenza vaccine is well tolerated and induces a robust immune response in healthy adults between the ages of 18 and 64. For adults aged 65 and over, the immune response to 2009 H1N1 influenza vaccine is somewhat less robust, as is the case with seasonal influenza vaccines.

We note that the slight discrepancies seen in our trials between the Sanofi Pasteur and CSL Limited vaccines may be due to technical differences in the preliminary measurement of the amounts of antigen in the doses used in the clinical trial lots and the relatively limited numbers of samples studied to date, as well as the fact that our data are drawn from a very early time point after immunization.

NIAID will continue to provide timely updates on these trials as well as those in children and in pregnant women, which began later.

Information from the NIAID studies will help inform the development of recommendations for immunization schedules, including the optimal dosage and number of doses for different age groups.

NIAID is conducting these clinical trials through its longstanding vaccine clinical trials infrastructure: the Vaccine and Treatment Evaluation Units, a network of medical centers that offers rapid response capability to test vaccines for emerging public health concerns. Detailed information is available from the NIAID Web site (www.niaid.nih.gov) and from http://ClinicalTrials.gov.

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Arteries Have Unique Immune Functions

Human arteries play distinct roles in the immune system depending on their anatomical location, researchers at Emory University School of Medicine have discovered.

Their findings explain why vascular diseases affect different parts of the arterial network and could help doctors fine-tune the treatment of such diseases as atherosclerosis and vasculitis. Atherosclerosis causes heart attacks and strokes because it occurs preferentially in arteries supplying the heart and the brain.

The results were published online this week by the journal Circulation.

Arteries can play an active role in sensing foreign invasion and bodily injury, because cells embedded in the arterial walls called dendritic cells act like smoke-sensing fire alarms for the immune system, says senior author Cornelia Weyand, MD. PhD, co-director of the Kathleen B. and Mason I. Lowance Center for Human Immunology at Emory University.

"All of our major arteries have this alarm system," she says. "To our surprise, we found that the arteries of the neck, the arms, the abdomen and the legs are triggered by different infectious organisms. Thus, each artery functions in a specialized way."

Some vascular diseases attack arteries only in the abdomen or in the neck and upper extremities, and this selectivity has puzzled doctors for years, Weyand says.

To probe the differences among arteries, Weyand and her co-workers examined the activity of genes that encode Toll-like receptors in blood vessels from human donors.

Toll-like receptors are a cornerstone of the "innate" immune system, which can be activated by common features of infection-causing invaders. The capture of bacterial or viral fragments through Toll-like receptors alerts the immune system early during an infectious attack. Toll-like receptors can respond to whip-like antennas on bacteria called flagellae, parts of bacterial cell walls, or DNA and RNA that leaks from viruses or bacteria.

Each type of artery had a different set of Toll-like receptor genes turned on, the authors found. In contrast to arteries, veins could not be stimulated through Toll-like receptors.

For example, cells in the iliac arteries, located in the vicinity of the gut, respond avidly to flagellae but cells from the subclavian arteries, which transport blood to the upper body, do not.

A possible explanation is that dendritic cells from iliac arteries are better able to sense flagellae because of the abundant bacterial flora that inhabits the gut, Weyand says.

Weyand hypothesizes that the dendritic cells in arteries are mainly performing a protective, calming function. Arteries are in constant contact with blood borne infectious agents, with potentially dangerous consequences of damaging the vessel wall.

"It's when that protective function breaks down that we see inflammation and various vascular diseases," she says.

She says her team is now investigating how the dendritic cells in arteries move and change as they receive various signals.

The first author of the paper is research specialist Olga Pryshchep, with contributions from postdoctoral fellow Wei Ma-Krupa, PhD, Joerg Goronzy, MD, PhD, co-director of the Lowance Center, and Brian Younge, MD, of the Mayo Clinic.

The research team used samples from 37 deceased donors with an average age of 64. Only arterial samples without atherosclerotic lesions were used.

The research was funded by the National Institutes of Health, the Dana Foundation and the McIntyre Family Discovery Fund.

Reference: Vessel-specific Toll-like receptor profiles in human medium and large arteries Circulation, Sep 2008; doi:10.1161/CIRCULATIONAHA.108.789172

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Studies Highlight MRSA Evolution and Resilience

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are caused primarily by a single strain — USA300 — of an evolving bacterium that has spread with "extraordinary transmissibility" throughout the United States during the past five years, according to a new study led by National Institutes of Health (NIH) scientists. CA-MRSA, an emerging public health concern, typically causes readily treatable soft-tissue infections such as boils, but also can lead to life-threatening conditions that are difficult to treat.

The study, from the National Institute of Allergy and Infectious Diseases (NIAID) of NIH, resolves debate about the molecular evolution of CA-MRSA in the United States. The findings rule out the previously held possibility that multiple strains of USA300, the most troublesome type of CA-MRSA in the United States, emerged randomly with similar characteristics. The study also offers a hypothesis for the origin of previous S. aureus outbreaks, such as those caused by penicillin-resistant strains in the 1950s and 1960s.

A second study led by the same NIAID scientists takes the issue of the evolution of MRSA a step further, revealing new information about how MRSA bacteria in general, including the USA300 group, elude the human immune system.

The first study, which appears online this week in the Proceedings of the National Academy of Sciences, found that the USA300 group of CA-MRSA strains, collectively called the epidemic strain, comprises nearly identical clones that have emerged from a single bacterial strain. It is the first time scientists have used comparative genome sequencing to reveal the origins of epidemic CA-MRSA. Frank R. DeLeo, Ph.D., at NIAID's Rocky Mountain Laboratories (RML) in Hamilton, Mont., led the research.

"Scientists are pressing ahead quickly to learn more about how some MRSA strains evade the immune system and spread rapidly," says NIAID Director Anthony S. Fauci, M.D. "The information presented in these two studies adds important new insights to that expanding knowledge base."

To understand how CA-MRSA is evolving in complexity and spreading geographically, Dr. DeLeo's group sequenced the genomes of 10 patient samples of the USA300 bacterium recovered from individuals treated at different U.S. locations between 2002 and 2005. They then compared these genomes to each other and to a baseline USA300 strain used in earlier studies. Eight of the 10 USA300 patient samples were found to have nearly indistinguishable genomes, indicating they originated from a common strain. The remaining two bacteria were related to the other eight, but more distantly.

Interestingly, of the eight nearly indistinguishable USA300 patient samples, two caused far fewer deaths in laboratory mice than the others, highlighting an emerging view that tiny genetic changes among evolving strains can profoundly affect disease severity and the potential for drug resistance to develop.

"The USA300 group of strains appears to have extraordinary transmissibility and fitness," says Dr. DeLeo. "We anticipate that new USA300 derivatives will emerge within the next several years and that these strains will have a wide range of disease-causing potential." Ultimately, Dr. DeLeo and his colleagues hope that the work will lead to the development of new diagnostic tests that can quickly identify specific strains of MRSA.

Fred C. Tenover, Ph.D., of the Centers for Disease Control and Prevention in Atlanta (CDC) contributed the 10 USA300 clinical isolates from CDC's Active Bacterial Core Surveillance system. Other study collaborators included Barry N. Kreiswirth, Ph.D., of the International Center for Public Health (ICPH) in Newark, N.J., and James M. Musser, M.D., Ph.D., of The Methodist Hospital Research Institute in Houston.

The second report, which involved scientists from RML, ICPH and Vanderbilt University Medical Center in Nashville, was recently published online in the Journal of Immunology. This study provides scientists with new details about the complex mechanisms MRSA uses to avoid destruction by neutrophils, human white blood cells that ingest and destroy microbes. When exposed to hydrogen peroxide, hypochlorous acid (the active component of household bleach) or antimicrobial proteins — all killer chemicals released by neutrophils — MRSA senses danger, escapes harm and turns the tables on the white blood cells, destroying them. Work is continuing in Dr. DeLeo's lab to understand how the bacterium senses and survives attacks by neutrophils.

NIAID is a component of the National Institutes of Health. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on basic immunology, transplantation and immune-related disorders, including autoimmune diseases, asthma and allergies.