Mosquito bites deliver potential new malaria vaccine

Sep. 11, 2013 — A study published in Vaccine could provide hope for new live-attenuated malaria vaccineThis study suggests that genetically engineered malaria parasites that are stunted through precise gene deletions (genetically attenuated parasites, or “GAP”) could be used as a vaccine that protects against malaria infection. This means that the harmless (attenuated) version of the parasite would interact with the body in the same way as the infective version, but without possibility of causing disease. GAP-vaccination would induce robust immune responses that protect against future infection with malaria.According to the World Health Organization, there were 219 million documented cases of malaria in 2010, causing the deaths of up to 1.2 million people worldwide. Antimalarial treatments are available to reduce the risk of infection, but as yet there is no effective vaccine against the disease.Last month, a team of scientists announced the results of a trial with a new kind of malaria vaccine, a whole-parasite preparation weakened by radiation. The trial showed promising results, but the method of vaccination was not optimal, requiring intravenous administration and multiple high doses. This current paper outlines a method of attenuation through genetic engineering rather than radiation, which offers hope for a more consistent vaccine that gives better protection.”Malaria is one of the world’s biggest killers, and threatens 40 percent of the world’s population, yet still no effective vaccine exists,” said Stefan Kappe, Ph.D., lead author of the paper and professor at Seattle BioMed. “In this paper we show that genetically engineered parasites are a promising, viable option for developing a malaria vaccine, and we are currently engineering the next generation of attenuated parasite strains with the aim to enter clinical studies soon.”For the first time, researchers created a weakened version of the human malaria parasite by altering its DNA. They tested the safety of the new modified parasite by injecting six human volunteers through mosquito bites. Five of the six volunteers showed no infection with the parasite, suggesting that the new genetic technique has potential as the basis for a malaria vaccine.”Our approach offers a new path to make a protective malaria vaccine that might overcome the limitations of previous development attempts. …

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Pain-free microneedle influenza vaccine is effective, long-lasting

Sep. 4, 2013 — Scientists have developed an influenza vaccine delivered via microneedle patch that provided 100 percent protection against a lethal influenza virus in mice more than one year after vaccination. They report their findings in the September 2013 issue of the journal Clinical and Vaccine Immunology.Share This:Microneedles are a medium for delivery of influenza vaccine that avoids the pain associated with ordinary hypodermic needles. They are a mere seven tenths of a millimeter in length, and the volume of vaccine — a major contributor to pain — is minuscule.Instead of a liquid containing whole killed or attenuated virus, this vaccine uses dry virus-like particles (VLPs) which simply coat the needles in the presence of a simple stabilizing agent, reducing the need for refrigeration — a potential boon for use in developing countries. The lower dose required when using microneedles also reduces the potential for side effects, such as lung inflammation.”This method can induce higher levels of IgG2a antibodies as well as rapid recall immune responses following lethal challenge infection. Our previous study showed that microneedle vaccination induced higher levels of antibody-secreting cells in spleen and bone marrow compared to intramuscular vaccination,” says Sang-Moo Kang of Georgia State University, a researcher on the study.Earlier studies by this group showed that influenza VLP-coated microneedles actually produced higher short-term protection than conventional intramuscular immunization. In this study the researchers tested how effective the long-term protection of the vaccine was. Mice that received the vaccine were 100 percent protected from a lethal challenge with the influenza virus 14 months after vaccination.Kang says his aim was to develop an easier and pain-free method of vaccine delivery. He also says that patients could probably use this system to vaccinate themselves.Share this story on Facebook, Twitter, and Google:Other social bookmarking and sharing tools:|Story Source: The above story is based on materials provided by American Society for Microbiology. Note: Materials may be edited for content and length. …

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Investigational malaria vaccine found safe and protective

Aug. 8, 2013 — An investigational malaria vaccine has been found to be safe, to generate an immune system response, and to offer protection against malaria infection in healthy adults, according to the results of an early-stage clinical trial published Aug. 8 in the journal Science.The vaccine, known as PfSPZ Vaccine, was developed by scientists at Sanaria Inc., of Rockville, Md. The clinical evaluation was conducted by researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and their collaborators at the Walter Reed Army Institute of Research and the Naval Medical Research Center, both in Silver Spring, Md.Malaria is transmitted to humans by the bite of an infected mosquito. After the bite occurs, infectious malaria parasites in the immature, sporozoite stage of their life cycle first travel to the liver, where they multiply, and then spread through the bloodstream, at which time symptoms develop.The PfSPZ Vaccine is composed of live but weakened sporozoites of the species Plasmodium falciparum, the most deadly of the malaria-causing parasites.”The global burden of malaria is extraordinary and unacceptable,” said NIAID Director Anthony S. Fauci, M.D. “Scientists and health care providers have made significant gains in characterizing, treating and preventing malaria; however, a vaccine has remained an elusive goal. We are encouraged by this important step forward.”The Phase I trial, which took place at the NIH Clinical Center in Bethesda, received informed consent from and enrolled 57 healthy adult volunteers ages 18 to 45 years who never had malaria. Of these, 40 participants received the vaccine and 17 did not. To evaluate the vaccine’s safety, vaccinees were split into groups receiving two to six intravenous doses of PfSPZ Vaccine at increasing dosages. …

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New modular vaccine design combines best of existing vaccine technologies

July 29, 2013 — A new method of vaccine design, called the Multiple Antigen Presentation System (MAPS), may result in vaccines that bring together the benefits of whole-cell and acellular or defined subunit vaccination. The method, pioneered by researchers at Boston Children’s Hospital, permits rapid construction of new vaccines that activate mulitple arms of the immune system simultaneously against one or more pathogens, generating robust immune protection with a lower risk of adverse effects.As reported by Fan Zhang, PhD, Ying-Jie Lu, PhD, and Richard Malley, MD, from Boston Children’s Division of Infectious Disease, in the Proceedings of the National Academy of Sciences on July 29, the method could speed development of new vaccines for a range of globally serious pathogens, or infectious agents.Broadly speaking, the vaccines available today fall into two categories: whole-cell vaccines, which rely on weakened or killed bacteria or viruses; and acellular or subunit vaccines, which include a limited number of antigens — portions of a pathogen that trigger an immune response. Both approaches have advantages and disadvantages.”Whole-cell vaccines elicit a broad range of immune responses, often just as an infection would, but can cause side effects and are hard to standardize,” said Malley. “Acellular vaccines can provide good early immunity with less risk of side effects, but the immune responses they induce wane with time.”The MAPS method may allow vaccine developers to take a middle ground, where they can link multiple protein and polysaccharide (sugar) antigens from one or more pathogens together in a modular fashion, much as one would connect Lego blocks.The resulting complex — which resembles a scaffold of polysaccharides studded with proteins — can stimulate both antibody and T-cell responses simultaneously much like whole-cell vaccines, resulting in stronger immunity to the source pathogen(s). However, because the composition of a MAPS vaccine is well defined and based on the use of isolated antigens (as one would find with an acellular vaccine) the risk of side effects should be greatly reduced.For instance, mice injected with a MAPS vaccine combining proteins from tuberculosis (TB) and polysaccharides from Streptococcus pneumoniae (pneumococcus) mounted vigorous antibody and T-cell responses against TB, whereas those vaccinated with TB protein antigens alone mounted only an antibody response.Similarly, 90 percent of mice given a MAPS-based vaccine containing multiple pneumococcal polysaccharide and protein antigens were protected from a lethal pneumococcus infection, mounting strong antibody and T-cell responses against the bacteria. By contrast, 30 percent of mice vaccinated with the same antigens in an unbound state survived the same challenge.”The MAPS technology gives you the advantages of: whole-cell vaccines while being much more deliberate about which antigens you include; doing it in a quantitative and precise way; and including a number of antigens so as to try to replicate the effectiveness of whole-cell vaccination,” Malley explained. “The immunogenicity of these constructs is greater than the sum of their parts, somewhat because they are presented to the host as particles.”The system relies on the interactions of two compounds, biotin and rhizavidin, rather than covalent binding as is used in most of the current conjugate vaccines. To build a MAPS vaccine, biotin is bound to the polysaccharide(s) of choice and rhizavidin to the protein(s). The biotin and rhizavidin then bind together through an affinity interaction analogous to Velcro. The construction process is highly efficient, significantly reducing the time and cost of vaccine development and production.While his team’s initial work has focused on bacterial pathogens, Malley believes the technology could impact vaccine development for a broad range of pathogens, in particular those of importance in the developing world. …

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HIV/AIDS vaccines: Defining what works

July 18, 2013 — Designing an effective HIV/AIDS vaccine is something of a paradox: a good vaccine would be safe and look enough like HIV to kick-start the immune system into neutralizing the virus — but the problem is that this is exactly what the human immune system has trouble doing even when it’s exposed to the real thing.Now a team of researchers led by scientists at The Scripps Research Institute in La Jolla, CA has developed a strategy for inducing a key part of an effective immune response to HIV. By tracing the evolution of HIV-recognizing molecules called antibodies taken from the blood of rare individuals whose immune systems are naturally able to target and neutralize the virus, they may have found a way to replicate this for everybody.At a talk next week at the American Crystallographic Association meeting in Hawaii, the team will present multiple crystal structures, which like detailed architectural blueprints show how the virus interacts with components of the immune system. Examining these structures has allowed them to reverse engineer molecules that specifically activate the precursors of effective, neutralizing antibodies against the virus — molecules that may be components of a future vaccine against HIV.”What we tried to do was to learn how those [effective] antibodies developed over the course of natural infection and attempt to guide the immune response in the direction of what we know works in certain HIV-infected individuals,” said structural biologist Jean-Philippe Julien, who is presenting the work in Hawaii.He conducted the research under the direction of Professors Ian Wilson and William Schief of The Scripps Research Institute. The work was funded by the International AIDS Vaccine Initiative Neutralizing Antibody Center, the Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery and the National Institute of Allergy and Infectious Diseases (one of the National Institutes of Health). Additional support was provided through a Canadian Institutes of Health Research fellowship.Julien cautioned that the work might not, by itself, be the final answer that shows how to make an effective HIV/AIDS vaccine — but it is a step in the right direction. Most likely, Julien said, any future HIV/AIDS vaccine would combine multiple biological components in order to give the broadest possible protection against the virus.He added that their candidate molecule was able to achieve the desired immune reactions in the test tube, and they are currently testing it in animals to see if it is able to kick start the desired immune response. If those experiments go well, he said, further studies will examine whether it can protect animals against infection, and human trials for safety and vaccine efficacy would be next — though it may be years before those results are known.While designing a vaccine against any pathogen is a long, hard process, HIV has been particularly difficult, and despite decades of efforts and hundreds of millions of dollars spent in the process, we still do not yet have an effective vaccine that can prevent infection.

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