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


New rules for anticancer vaccines
Scientists have found a way to find the proverbial needle in the cancer antigen haystack, according to a report published in The Journal of Experimental Medicine.

A New Way to Prevent the Spread of Devastating Diseases
For decades, researchers have tried to develop broadly effective vaccines to prevent the spread of illnesses such as HIV, malaria, and tuberculosis.

Research yields a game changer for improving understanding of Ebola and great apes
A group of international scientists have developed a new method to study Ebola virus in wildlife.

Evolution of responses to (un)fairness
The sense of fairness did not evolve for the sake of fairness per se but in order to reap the benefits of continued cooperation, so say Frans de Waal, PhD, and Sarah Brosnan, PhD, co-authors of a review article about inequity aversion (IA), which is defined as a negative reaction to unequal outcomes.

Technique to model infections shows why live vaccines may be most effective
Vaccines against Salmonella that use a live, but weakened, form of the bacteria are more effective than those that use only dead fragments because of the particular way in which they stimulate the immune system, according to research from the University of Cambridge published today in the journal PLOS Pathogens.

Experts call for massive global response to tackle Ebola
The current Ebola outbreak now requires a "rapid response at a massive global scale", according to experts at the London School of Hygiene & Tropical Medicine.

The Search for Ebola Immune Response Targets
The effort to develop therapeutics and a vaccine against the deadly Ebola virus disease (EVD) requires a complex understanding of the microorganism and its relationship within the host, especially the immune response.

Targeted immune booster removes toxic proteins in mouse model of Alzheimer's disease
Alzheimer's disease experts at NYU Langone Medical Center and elsewhere are reporting success in specifically harnessing a mouse's immune system to attack and remove the buildup of toxic proteins in the brain that are markers of the deadly neurodegenerative disease.

Use of dengue vaccine may cause short-term spikes in its prevalence
As researchers continue to work toward vaccines for serious tropical diseases such as dengue fever, experts caution in a new report that such vaccines will probably cause temporary but significant spikes in the disease in the years after they are first used.

Synthetic messenger boosts immune system
Specific immune cells, known as T lymphocytes, have to be activated so that the body can develop long-term protection against 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...

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.

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...

What Your Doctor May Not Tell You About(TM) Children's Vaccinations

What Your Doctor May Not Tell You About(TM) Children's Vaccinations
by Stephanie Cave (Author), Deborah Mitchell (Contributor)


This is an essential guide for parents about vaccinations. Dr. Stephanie Cave explains their pros and cons and the book provides information to help parents make a knowledgeable, responsible choice about vaccinating their children.

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.

Make an Informed Vaccine Decision for the Health of Your Child: A Parent's Guide to Childhood Shots

Make an Informed Vaccine Decision for the Health of Your Child: A Parent's Guide to Childhood Shots
by Mayer Eisenstein (Author)


The current schedule of recommended vaccines is so crowded that doctors give babies several shots during a single office visit -- up to eight vaccines all at one time. Parents -- and doctors -- often forget that vaccines are drugs. How often do we, as adults, take that many drugs at the same time? Would we be more surprised if we did or did not have an adverse reaction? Dr. Mayer Eisenstein has practiced medicine, delivered babies, and provided families with preventive healthcare services for over 35 years. This honest guide to childhood shots was written especially for concerned parents. With Dr. Eisenstein's help, it is now possible to make informed vaccine decisions. In this book you will learn... * The prevalence and seriousness of each disease, including who is most at risk. * How...

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...

© 2014 BrightSurf.com