Science Current Events | Science News | Brightsurf.com
 

Advanced genetic screening method may speed vaccine development

May 10, 2012
Infectious diseases-both old and new-continue to exact a devastating toll, causing some 13 million fatalities per year around the world.

Vaccines remain the best line of defense against deadly pathogens and now Kathryn Sykes and Stephen Johnston, researchers at Arizona State University's Biodesign Institute, along with co-author Michael McGuire from the University of Texas Southwestern Medical Center are using clever functional screening methods to attempt to speed new vaccines into production that are both safer and more potent.

In a recent study appearing in the journal Proteome Science, the group used high-throughput methods to identify a modulator of immune activity that exists naturally in an unusual pathogen belonging to the Poxviridae family of viruses.

Parapoxvirus infection causes immune cell accumulation at the site of infection; direct screening in the host for this biological activity enabled the isolation of an immunomodulator-labeled B2. Indeed, B2 by itself causes immune cell accumulation at the site of skin injection. When added to a traditional influenza vaccine, B2 improves the vaccine's protective capacity. Furthermore, the immunomodulator also demonstrated the ability to shrink the size of cancerous tumors, even in the absence of any accompanying specific antigen.

In the past, the process of vaccine discovery involved the random selection of naturally attenuated strains of viruses and bacteria, which were found to provide protection in humans. Examples of this approach include the use of vaccinia to protect against smallpox and attenuated mycobacterium bovis (BCG) to protect against tuberculosis.

In recent years, many vaccines have been developed using only selected portions of a given pathogen to confer immunity. These so-called subunit vaccines have several advantages over whole pathogen vaccines. Genetic components that allow a given pathogen to elude immune detection for example may be screened out, as well as any factors causing unwanted vaccine side effects. Through careful screening, just those elements responsible for eliciting protective immune responses in the host can be extracted from the pathogen and reassembled into an effective, safer subunit vaccine.

In practice, the process of narrowing the field of promising subunit candidates from the whole genome of a pathogen has often been time consuming, laborious and perplexing. In the current study, their earlier-developed strategy, known as expression library immunization, is extended to develop a scheme to find the protein-encoding segments-known as open reading frames (ORFs)-from a pathogenic genome that have any biological function of interest.

This simple, yet powerful technique uses the host's immune system itself to rapidly reduce any pathogenic genome (viral, fungal, bacterial or parasitic) to a handful of antigens capable of conferring protection in the host.

The advantage of this in vivo technique is that it offers a means of rapidly screening entire genomes, with the results of the search displaying desired immunogenic traits. The mode of entry of vaccines designed in this way closely resembles the natural infection process of host cells-an improvement over live attenuated vaccines.

This promising approach has been used effectively to engineer a vaccine against hepatitis and may provide a new avenue for the development of protective agents against pathogens that have thus far eluded traditional vaccine efforts, including HIV and ebola.

"We had developed a method for screening for protective subunits against a specific disease," Sykes says. "However this type of safer vaccine design is notoriously less potent than the whole pathogen designs. What we needed was a method to find generally useful vaccine components that would serve to enhance and control immunity."

The group chose the pathogen parapoxvirus ovis (known as the Orf virus) for the current set of experiments, in which expression library immunization techniques were used to screen for an immunogenic factor buried in the pathogen's genome.

Parapoxvirus ovis causes a highly infectious disease known as Orf, which is prevalent in sheep and goats and may be transmitted cutaneously to humans handling these animals, causing pustular lesions and scabs.

Once the group had sequenced the full genome of parapoxvirus, PCR was used to amplify all the viral open reading frames, which code for all of the viruse's proteins. Each ORF, comprising a library of genomic components, was compiled into a unique high throughput expression construct, and these were randomly distributed into sub-library pools. These pools were directly delivered into sets of mice for in vivo expression. Functional testing for the activity desired identified B2 as the immune cell accumulator.

In further experiments, the team co-delivered B2L as an additive or adjuvant for an influenza gene vaccine, to see if it could improve survival rates in mice challenged with the influenza virus. The co-immunized mice indeed displayed full protection against influenza compared with 50 percent protection of the control group, immunized with influenza vaccine alone.

In addition to infectious agents like Orf, non-infectious diseases including cancer may be amenable to vaccine defense. Thus far however, the discovery of tumor-specific antigens has been frustrating. One approach may lie in using non-specific immunogenic factors like B2.

In the current study, two forms of cancer were investigated in a mouse model, following the administering of B2 alone, in the absence of a disease antigen. The experiments evaluated B2's ability to enhance survival and shrink tumor size. In the case of an aggressive melanoma, tumor size was significantly reduced and survival rate improved. Administration of B2 to an infection induced by a breast cancer cell line also showed a modest but measureable reduction in tumor size.

With the growing popularity of sub-unit vaccines, the need arises for more effective adjuvants, which may be used to compensate for the reduced immunogenicity of such vaccines compared with their whole-pathogen counterparts. Techniques similar to those applied here to isolate and evaluate B2 could potentially permit the screening of virtually any genome for any gene-encoded activity testable in an organism.

Arizona State University


Related Vaccines Current Events and Vaccines News Articles


More attention to measles, vaccine experts urge
Doctors and public health authorities need to renew their attention to measles, researchers from Emory Vaccine Center urge in an editorial in the New England Journal of Medicine.

Politics can interact with evolution to shape human destiny
Politics can have unintentional evolutionary consequences that may cause hastily issued policies to cascade into global, multigenerational problems, according to political scientists.

You are here: Home / News / GW Researcher Adapting Breakthrough Technologies to Combat... GW Researcher Adapting Breakthrough Technologies to Combat Parasitic Worm Infections
Recent breakthroughs may pave the way for vaccines and new drugs for those infected by parasitic helminths.

Ebola's evolutionary roots more ancient than previously thought, study finds
A new study is helping to rewrite Ebola's family history. The research shows that filoviruses - a family to which Ebola and its similarly lethal relative, Marburg, belong - are at least 16-23 million years old.

The Ebola epidemic: Is there a way out?
Not everyone who contracts the Ebola virus dies, the survival rate is around 30% suggesting that some kind of immunity to the disease is possible. Experimental treatments and vaccines against Ebola exist but have not yet been tested in large groups for safety and efficacy (phase 2 trials).

Clinical results indicate vaccine candidate highly efficacious against bacterial diarrhea
New results from a safety and immunogenicity study, which included a challenge phase to test efficacy, indicate that a live attenuated enterotoxigenic Escherichia coli (ETEC) vaccine candidate, given in combination with a novel adjuvant, provided significant protection against disease.

The Lancet Infectious Diseases: Study predicts that current international commitments will not contain Ebola outbreak in Montserrado, Liberia
New modeling research, published in The Lancet Infectious Diseases journal, has found that the number of Ebola treatment center beds and other measures needed to control the epidemic in Montserrado County, Liberia substantially exceeds the total pledged by the international community to date.

Flu Vaccine May Hold Key to Preventing Heart Disease
Flu vaccines are known to have a protective effect against heart disease, reducing the risk of a heart attack. For the first time, this research, published in Vaccine, reveals the molecular mechanism that underpins this phenomenon. The scientists behind the study say it could be harnessed to prevent heart disease directly.

Scientists take step towards drug to treat norovirus stomach bug
An experimental drug currently being trialled for influenza and Ebola viruses could have a new target: norovirus, often known as the winter vomiting virus. A team of researchers at the University of Cambridge has shown that the drug, favipiravir, is effective at reducing - and in some cases eliminating - norovirus infection in mice.

Once CD8 T cells take on one virus, they'll fight others too
Scientists think of CD8 T cells as long-lived cells that become tuned to fight just one pathogen, but a new study finds that once CD8 T cells fight one pathogen, they also join the body's "innate" immune system, ready to answer the calls of the cytokine signals that are set off by a wide variety of infections.
More Vaccines Current Events and Vaccines News Articles

The Vaccine Book: Making the Right Decision for Your Child (Sears Parenting Library)

The Vaccine Book: Making the Right Decision for Your Child (Sears Parenting Library)
by Robert W. Sears (Author)


THE VACCINE BOOK offers parents a fair, impartial, fact-based resource from the most trusted name in pediatrics. Dr. Bob devotes each chapter in the book to a disease/vaccine pair and offers a comprehensive discussion of what the disease is, how common or rare it is, how serious or harmless it is, the ingredients of the vaccine, and any possible side effects from the vaccine. This completely revised edition offers

· updated information on each vaccine and disease

· more detail on vaccines' side effects

· expanded discussions of combination vaccines

· a new section on adult vaccines

· additional options for alternative vaccine schedules

· a guide to Canadian vaccinations

THE VACCINE BOOK provides exactly the...

Vaccine Epidemic: How Corporate Greed, Biased Science, and Coercive Government Threaten Our Human Rights, Our Health, and Our Children

Vaccine Epidemic: How Corporate Greed, Biased Science, and Coercive Government Threaten Our Human Rights, Our Health, and Our Children
by Louise Kuo Habakus (Editor), Mary Holland (Editor), Kim Mack Rosenberg (Editor)


Public health officials state that vaccines are safe and effective, but the truth is far more complicated. Vaccination is a serious medical intervention that always carries the potential to injure and cause death as well as to prevent disease. Coercive vaccination policies deprive people of free and informed consent—the hallmark of ethical medicine. Americans are increasingly concerned about vaccine safety and the right to make individual, informed choices together with their healthcare practitioners. Vaccine Epidemic focuses on the searing debate surrounding individual and parental vaccination choice in the United States.

Habakus, Holland, and Rosenberg edit and introduce a diverse array of interrelated topics concerning the explosive vaccine controversy, including...

Dissolving Illusions: Disease, Vaccines, and The Forgotten History

Dissolving Illusions: Disease, Vaccines, and The Forgotten History
by Suzanne Humphries MD (Author), Roman Bystrianyk (Author)


Not too long ago, lethal infections were feared in the Western world. Since that time, many countries have undergone a transformation from disease cesspools to much safer, healthier habitats. Starting in the mid-1800s, there was a steady drop in deaths from all infectious diseases, decreasing to relatively minor levels by the early 1900s. The history of that transformation involves famine, poverty, filth, lost cures, eugenicist doctrine, individual freedoms versus state might, protests and arrests over vaccine refusal, and much more. Today, we are told that medical interventions increased our lifespan and single-handedly prevented masses of deaths. But is this really true? Dissolving Illusions details facts and figures from long-overlooked medical journals, books, newspapers, and other...

Vaccines: Expert Consult - Online and Print, 6e (Vaccines (Plotkin/ Orenstein))

Vaccines: Expert Consult - Online and Print, 6e (Vaccines (Plotkin/ Orenstein))
by Stanley A. Plotkin MD (Author), Walter Orenstein MD (Author), Paul A. Offit MD (Author)


2013 BMA Medical Book Awards Highly Commended in Public Health! Apply the latest vaccination knowledge with a reference that Bill Gates calls "an indispensable guide to the enhancement of the well-being of our world." Inside Vaccines, you'll find comprehensive and current coverage of every aspect of vaccination, from the development of each vaccine to its use in reducing disease. This medical reference book offers the expert information you need to apply the very latest techniques and information in your practice!Gain a complete understanding of each disease, including clinical characteristics, microbiology, pathogenesis, diagnosis, and treatment, as well as epidemiology and public health and regulatory issues.Update your knowledge of both existing vaccines and vaccines currently in the...

Vaccine Free: 111 Stories of Unvaccinated Children

Vaccine Free: 111 Stories of Unvaccinated Children
by Andreas Bachmair (Author)


Vaccine Free - 111 Stories of Unvaccinated Children is a moving testament to the power of the body to take care of itself and the trust that people put in that natural process. In this book, based on research with more than 15000 participants from all over the world (www.vaccineinjury.info), you will find stories of families who investigated the vaccine topic carefully and thoroughly because they love and want to protect their children. These stories will educate you to not follow public opinion and propaganda but rather question what is happening and become informed when making decisions that pertain to the health of your children and our future generations.

I strongly recommend this book, knowing that the time you spend reading it will be time well spent, an investment in...

Vaccines Are They Really Safe and Effective?

Vaccines Are They Really Safe and Effective?
by Neil Z. Miller (Author)


This bestselling immunization handbook (new, updated 2012 edition) evaluates each vaccine for safety, efficacy, and long-term effects. It contains the most comprehensive, up-to-date, uncensored data available -- information that many doctors don't even know. It includes the most recent studies, several case histories detailing vaccine-induced damage to children, and pinpoints for parents exact conditions that may put their own child at high risk. In addition, health alternatives are offered, along with legal options to mandatory shots. It contains 30 graphs and diagrams plus more than 900 footnotes and scientific references so that all of the information may be confirmed. Parents, educators, health professionals, and other concerned individuals have very few sources of information...

Vaccine Illusion

Vaccine Illusion


Due to the growing number of vaccine safety concerns, our society has been polarized into vaccine advocates and vaccine opponents. However, in the debate over vaccine safety, we have lost sight of a bigger problem: how vaccination campaigns wipe out our herd immunity and endanger the very young. Written by an immunologist, Vaccine Illusion explains why vaccines cannot give us lasting immunity to infectious diseases and how they jeopardize our natural immunity and overall health.

Disclaimer: The information in this book is not intended as medical advice. Readers assume sole responsibility for choosing for themselves and their children disease prevention options that are compatible with their convictions.

Vaccine Safety Manual for Concerned Families and Health Practitioners, 2nd Edition: Guide to Immunization Risks and Protection

Vaccine Safety Manual for Concerned Families and Health Practitioners, 2nd Edition: Guide to Immunization Risks and Protection
by Neil Z. Miller (Author), Russell Blaylock (Foreword)


The Vaccine Safety Manual (new, updated 2012 edition) is the worlds most complete guide to immunization risks and protection. It includes pertinent information on every major vaccine: polio, tetanus, MMR, hepatitis A, B, HPV (cervical cancer), Hib, Flu, chickenpox, shingles, rotavirus, pneumococcal, meningococcal, RSV, DTaP, anthrax, smallpox, TB, and more. All of the information, including detailed vaccine safety and efficacy data, is written in an easy-to-understand format, yet includes more than 1,000 scientific citations. More than 100 charts, tables, graphs and illustrations supplement the text. This encyclopedic health manual is an important addition to every family's home library and will be referred to again and again.

Deadly Choices: How the Anti-Vaccine Movement Threatens Us All

Deadly Choices: How the Anti-Vaccine Movement Threatens Us All
by Paul A. Offit M.D. (Author)


In 2010, California suffered the largest and deadliest outbreak of pertussis, also known as “whooping cough,” in more than fifty years. This tragedy was avoidable. An effective vaccine has been available since the 1940s. In recent years other diseases, like measles and mumps, have also made a comeback. The reason for these epidemics can be traced to a group whose vocal proponents insist, despite evidence to the contrary, that vaccines are poison. As a consequence, parents and caretakers are rejecting vaccines for themselves and their families.In Deadly Choices, infectious-disease expert Paul Offit takes a look behind the curtain of the anti-vaccine movement. What he finds is a reminder of the power of scientific knowledge, and the harm we risk if we ignore it.

Saying No to Vaccines: A Resource Guide for All Ages

Saying No to Vaccines: A Resource Guide for All Ages
by Sherri J. Tenpenny (Author), NMA Media Press (Editor)


The most comprehensive guide explaining how and why vaccines are detrimental to your and your childs health. At a time when the vaccine controversey is becoming increasingly hostile, this book offers an in-depth examination of how Saying No to Vaccines can save your and your childs life. Well respected, Dr. Tenpenny is an Internationally recognized expert and the first physician to offer documented proof that vaccines do compromise the immune system. Dr. Tenpenny has the courage and the determination to express a minority view, substantiating her work with citations directly from Centers for Disease Control (CDC) documents and respected, peer-reviewed journals, offering irrefutable facts that fly in the face of information generally regarded as truth in traditional medical circles.

© 2014 BrightSurf.com