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Human Vaccines & Immunotherapeutics Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/khvi20
Human Vaccines & Immunotherapeutics: News Eva M Riedmann
a
a
Acquisitions Editor; Landes Bioscience; Vienna, Austria Published online: 15 May 2014.
Click for updates To cite this article: Eva M Riedmann (2014) Human Vaccines & Immunotherapeutics: News, Human Vaccines & Immunotherapeutics, 10:2, 252-255, DOI: 10.4161/hv.28444 To link to this article: http://dx.doi.org/10.4161/hv.28444
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Versions of published Taylor & Francis and Routledge Open articles and Taylor & Francis and Routledge Open Select articles posted to institutional or subject repositories or any other third-party website are without warranty from Taylor & Francis of any kind, either expressed or implied, including, but not limited to, warranties of merchantability, fitness for a particular purpose, or non-infringement. Any opinions and views expressed in this article are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor & Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/terms-and-conditions It is essential that you check the license status of any given Open and Open Select article to confirm conditions of access and use.
Policy& & Profiles News, News, Policy Profiles
Human Vaccines & Immunotherapeutics 10:2, 252–255; February 2014; © 2014 Landes Bioscience
Human Vaccines & Immunotherapeutics: News
Downloaded by [University of Bristol] at 03:35 27 February 2015
Recently approved pandemic and seasonal influenza vaccines The US Food and Drug Administration (FDA) recently approved the first adjuvanted vaccine for the prevention of H5N1 influenza, commonly known as avian or bird flu. The influenza A (H5N1) monovalent vaccine, developed by GSK, is indicated for use in adults who are at increased risk of exposure to the H5N1 influenza virus. Avian influenza is an infectious disease of birds caused by certain influenza A viruses. While most avian influenza A viruses do not infect people, some viruses, such as H5N1, have caused serious illness and death in people. According to the World Health Organization (WHO), about 60% of people infected with H5N1 die. The vaccine is not intended for commercial availability, but the US Department of Health and Human Services has purchased it for inclusion in the National Stockpile for distribution by public health officials if needed. “This vaccine could be used in the event that the H5N1 avian influenza virus develops the capability to spread efficiently from human to human, resulting in the rapid spread of disease across the globe,” said Dr Karen Midthun, director of the FDA’s Center for Biologics Evaluation and Research. “Vaccines are critical to protecting public health by helping to counter the transmission of influenza disease during a pandemic.” The FDA approval was based on a trial of 4500 adults, which showed that 91% of subjects aged 18-64 years had an antibody response consistent with protection against the H5N1 virus following immunization with two doses. The vaccine was less effective in people >65 years but still protected more than two-thirds of subjects in this age group. The vaccine was found to be safe, with the most common side effects reported being infection site pain, muscle aches, headache, fatigue,
and injection site redness and swelling. The FDA advisory panel had unanimously recommended the vaccine already one year ago, but approval was delayed because the vaccine is adjuvanted with AS03. This adjuvant was also used in GSK`s H1N1 vaccine, which has been linked to the development of narcolepsy, with ~800 cases of narcolepsy developing following immunization. Another recently approved influenza vaccine is AstraZeneca’s intranasal four-strain live attenuated seasonal vaccine for children and adolescents. The European Commission (EC) has granted Marketing Authorization to Fluenz Tetra, making it the first and only intranasal tetravalent influenza vaccine available in Europe. The EC decision follows a positive opinion from the Committee for Medicinal Products for Human Use and is applicable to all 28 member states and the three European Economic Area countries of the European Union. Until recently, seasonal vaccines have contained three strains of influenza: two A viruses and one B virus. Fluenz Tetra contains an additional B strain. Over the past decade, ~25% of circulating influenza strains in Europe were influenza B strains. “Fluenz Tetra represents the next generation of influenza vaccine and we are pleased that it is now approved in Europe,” said Dr Filip Dubovsky, Vice President of Clinical Biologics Infectious Disease and Vaccines at MedImmune, AstraZeneca’s global biologics research and development arm. “The inclusion of a second influenza B strain will broaden the coverage of Fluenz Tetra and should have a valuable public health impact.” Approval of Fluenz Tetra was based on data from a pivotal paediatric study, showing that Fluenz Tetra demonstrated a safety and immunogenicity profile that was comparable to Fluenz, a trivalent live attenuated vaccine
approved in Europe. Fluenz Tetra is planned to replace the trivalent vaccine Fluenz from the 2014-15 flu season onwards. In the US, Fluenz Tetra is marketed under the trade name FluMist Quadrivalent, approved since 2012. Finally, the New England Journal of Medicine published a study on the effectiveness of the quadrivalent influenza vaccine FluLaval in preventing seasonal flu in children.1 The study was one of the pivotal clinical trials leading to the recent FDA approval of GSK´s FluLaval Quadrivalent vaccine. The randomized, controlled clincial trial included >5200 children, and was the first large-scale study conducted specifically to review the safety and effectiveness of vaccinating children with a four-strain flu vaccine. FluLaval Quadrivalent was shown to reduce influenza cases among children aged 3-8 years by 55% overall and lowered the risk of developing moderate-to-serious flu illness by 73%. “The U.S. Centers for Disease Control recommends that all children get vaccinated each flu season. This is in response to how many children require flu-related medical care, and given that as many as 20 000 U.S. children are hospitalized each year due to complications of the flu,” said Dr Leonard Friedland, Vice President, Director Scientific Affairs and Public Health, GSK Vaccines North America. “This study provides robust safety and efficacy data on FluLaval Quadrivalent, and evidence of the clinical benefit of vaccination with FluLaval Quadrivalent as demonstrated by the prevention of moderate-to-severe cases of influenza among children.” Reference 1. Jain VK, et al. N Engl J Med 2013; 369:2481-91; PMID:24328444; http://dx.doi.org/10.1056/ NEJMoa1215817
Agenus cancer vaccine extends survival of GBM patients The biotechnology company Agenus recently published results from a Phase 2 clinical study, demonstrating that >90% of patients treated with the company‘s brain
252
cancer vaccine Prophage Series G-200 were alive at six months after surgery and 30% were alive at 12 months. Median overall survival (OS) was approximately 11 months.
Human Vaccines & Immunotherapeutics
Prophage Series vaccines are individualized heat shock protein-based therapeutic cancer vaccines, manufactured using a patient’s own tumor after surgical removal.
Volume 10 Issue 2
Downloaded by [University of Bristol] at 03:35 27 February 2015
Thus, each vaccine contains the antigenic fingerprint of a patient’s particular cancer. They are designed to activate the immune system to specifically target and destroy cancer cells bearing this fingerprint. In the current multi-center,single-arm Phase 2 study, 41 patients with surgically resectable recurrent Glioblastoma multiforme (GBM) were repeatedly immunized with Prophage Series G-200 to assess the survival rate at six months. GBM is the most common and aggressive form of primary brain cancer, and patients face a poor prognosis. Trial participant had surgery to remove ≥90% of their tumors, which were then used to manufacture Prophage Series G-200. The vaccine was given to patients once weekly for four weeks, followed by biweekly injections until vaccine depletion. The vaccine showed a good safety
profile. About 90% of treated patients were alive at 6 months following surgery, and 30% were still alive at 12 months. Median OS was approximately 11 months, which compares favorably to the expected median survival for recurrent GBM patients of 3–9 months. The data were recently published in the journal Neuro-Oncology.2 “Glioblastoma tumors are often resistant to standard therapies and the extended survival observed in patients treated with Prophage Series vaccine is very promising,” said Dr Andrew Parsa from the Feinberg School of Medicine at Northwestern University, corresponding author of the study. “The next phase of development is underway with an NCI funded, large-scale, randomized trial investigating Prophage Series G-200 in combination with Avastin (bevacizumab). Avastin
is approved for the treatment of recurrent GBM and we believe there is the potential for a synergistic effect of a targeted anti-tumor immunotherapy and anti-angiogenic agent that could benefit patients.” The ongoing ALLIANCE Trial, studying a combination of Prophage Series G-200 and Avastin, is the largest brain tumor trial ever funded by the NCI and the largest vaccine study ever conducted with Avastin (previously reported in HV&I news 9-10). The study aims to advance the treatment of GBM, the most common and malignant form of brain cancer. Reference 2. Bloch O, et al. Neuro Oncol 2014; 16:274-9; PMID:24335700; http://dx.doi.org/10.1093/ neuonc/not203
Influenza vaccines prevented over 6 million flu cases in the US In a recent report, the Centers for Disease Control and Prevention (CDC) estimated influenza illnesses and hospitalizations averted by influenza vaccination in the US during the 2012–13 flu season. 3 Based on CDC surveillance data, the 2012– 13 influenza season was characterized as moderately severe. Rates of influenza-associated hospitalizations were 42 per 100 000 persons, compared to 7.7–23.4 per 100 000 during the previous three seasons. 169 influenza-associated pediatric deaths (deaths among persons 60 years of age. The data showed that PPV23 does not provide any relevant benefit against AMI in this population. Cardiovascular benefits associated with PPV23 vaccination are controversial. The study published in a recent issue of the journal Vaccine6 is the first prospective study using validated clinical data to evaluate relationships between pneumococcal vaccination and risk of myocardial infarction. It is a follow-up of the CAPAMIS study, published in 2010, which aimed to clarify the controversial effect of PPV23 in preventing communityacquired pneumonia and the possible role of pneumococcal vaccination in cardiovascular prevention.7
254
A Spanish team of researchers conducted the population-based cohort study involving >27 000 individuals over age 60, who were prospectively followed for three years (from December 2008 to December 2011). Outcomes were hospitalization for AMI, 30-day mortality from AMI, and all-cause death. Cox regression was used to evaluate the association between pneumococcal vaccination and the risk of each outcome. Study subjects were followed for a total of 76 033 person-years, of which 29 065 were for vaccinated subjects. Overall, 359 cases of AMI, 55 deaths from AMI and 2465 all-cause deaths were observed. Pneumococcal vaccination did not alter the risk of AMI, death from AMI and all-cause death in the general population of people over 60 years. Analyses focused on people with and without history of prior coronary artery disease, showed that
Human Vaccines & Immunotherapeutics
pneumococcal vaccination did not emerge effective in preventing any analyzed event. In conclusion, this new study supports that PPV23 does not provide any relevant benefit against AMI in the general population >60 years, as in primary as well as in secondary prevention, although it is underpowered to exclude a small benefit of vaccination against rare outcomes. References 6. Ochoa-Gondar O, et al. Vaccine 2014; 32:2527; PMID:24262314; http://dx.doi.org/10.1016/j. vaccine.2013.11.017 7. Vila-Corcoles A, et al. BMC Public Health 2010; 10:25; PMID:20085658; http://dx.doi. org/10.1186/1471-2458-10-25
Volume 10 Issue 2
Downloaded by [University of Bristol] at 03:35 27 February 2015
Vical initiates vaccine trials against HSV-2 and CMV The San Diego-based biotech company Vical Incorporated recently announced the inititation of two clinical trials: a Phase 1/2 study of its therapeutic vaccine for herpes simplex virus type 2 (HSV-2), and a Phase 2 study of its cytomegalovirus (CMV) vaccine for solid organ transplant (SOT) recipients. HSV-2 is a sexually transmitted virus and the leading cause of recurrent genital herpes. Worldwide, one out of every six individuals aged 15 to 49 years is chronically infected with HSV-2. Persistent infection may result in periodic virus shedding placing sexual partners at risk of infection. It also can lead to debilitating genital lesions, which significantly increase the risk of acquiring HIV-1 virus from HIVinfected sexual partners. There is no approved vaccine for HSV. Vical will test its HSV-2 DNA vaccine, formulated with the company’s proprietary adjuvant Vaxfectin, in approximatly 150 healthy HSV-2-infected adults at six key US clinical sites. The randomized double-blind, placebocontrolled trial will evaluate safety, tolerability and efficacy of the vaccine. “The initiation of this trial represents another milestone for Vical,” said Dr Larry Smith, Vice President of Vaccine Research at Vical. “Our trial is designed to demonstrate
reductions in the rate of HSV-2 that is shed from individuals with symptomatic genital herpes. A therapeutic vaccine may be the ideal approach for reducing viral shedding because of the ability to harness the immune system to control HSV-2, potentially freeing subjects from daily, lifelong antiviral drug usage. This Phase 1/2 trial is a vital step towards developing a product that not only limits viral shedding but may also reduce both symptomatic genital herpes lesions as well as virus transmission.” The other recently initiated clinical trial tests a vaccine against CMV. This herpesvirus infects more than half of all adults in the US by age 40, and is even more widespread in developing countries. Healthy people are usually protected against CMV disease, even though they may be latent carriers. Individuals with impaired immune system function, including transplant patients, are at high risk of CMV reactivation, potentially leading to severe illness or death. Vical is developing its CMV vaccine ASP0113 (formerly TransVax) in collaboration with Astellas Pharma. The Japanese biopharmaceutical company is conducting the trial under an exclusive worldwide license agreement with Vical to develop and commercialize
ASP0113. Vical is providing development, regulatory and manufacturing support. The investigational bivalent DNA vaccine ASP0113 contains plasmids encoding human CMV pp65 and gB antigens and is designed to induce both cellular and humoral immune responses. A proprietary poloxamer-based delivery system is used for formulation. The randomized, double-blind, placebocontrolled Phase 2 trial is designed to evaluate the efficacy of ASP0113 compared to placebo as measured by the incidence of CMV viremia in CMV-seronegative subjects receiving a kidney from a CMV-seropositive donor. The study, include approximately 140 SOT recipients, will also evaluate the safety of ASP0113 in this patient population. Each subject will be followed-up for one year following enrollment. “Following the initiation of our Phase 3 trial of ASP0113 in hematopoietic cell transplant (HCT) recipients in June, we are pleased to expand the ASP0113 program with this Phase 2 trial in SOT recipients,” said Dr Bernie Zeiher, Senior Vice President and Global Therapeutic Area Head of Immunology and Infectious Diseases at Astellas Pharma Global Development, Inc. “The unmet medical need to control CMV in transplant recipients remains high.”
Fingerprint sensors to track vaccination records in developing countries The US company Lumidigm (Albuquerque, NM) in partnership with Fulcrum Biometrics (San Antonio, TX) has developed multispectral imaging fingerprint sensors that are helping to keep vaccination records up-to-date and stop vaccine wastage in developing countries. Vaccine delivery in low-resource countries has often been hampered by ineffective tracking and reporting, and consequently many young children are not being vaccinated. The delivery model in many parts of Africa depends on a multitude of healthcare workers who serve very large and remote areas. Lacking or incomplete vaccination records lead to many patients being re-immunized unnecessarily, while others are simply missed and a finite supply of vaccine is wasted. In some of the most challenging geographics, vaccine wastage is estimated to be >50%. VaxTrac, supported by The Bill and Melinda
www.landesbioscience.com
Gates Foundation among others, wants to solve this problem with a biometric vaccination registry that is operated and managed in the field with low-cost mobile devices. Adult and child patients are identified in the registry with fingerprint sensors from Lumidigm. With the simple touch of a finger, returning patients can pull up their vaccination records, allowing the healthcare worker to deliver appropriate care. The biometric vaccine registry also enables real-time reporting for streamlined supply-chain management, further reducing waste. “With our VaxTrac system leveraging Lumidigm fingerprint sensors, we have been able to improve immunization tracking, which allows us to reduce waste so that we can vaccinate more people and save lives,” asserts Dr Mark Thomas, executive director of VaxTrac. “We started evaluating Lumidigm sensors
in 2012. Since the skin of children, especially young children, can be very malleable, we knew from experience that conventional biometric technologies that need a finger pressed against the device do not work. The ability that Lumidigm offers to pull fingerprint images from deeper layers produces images less susceptible to distortion and allows us to track vaccinations accurately.” The first in-country deployment of the Lumidigm fingerprint sensors was in March 2013. The units are now in Kenya, Uganda and Benin, with the largest deployment in 40 clinics throughout Zambia. Community healthcare workers are trained to use the simple, user-friendly record system, especially developed for workers with limited literacy. Expensive, specialized training for vaccine delivery in remote areas is no longer necessary with the biometric VaxTrac system.
Human Vaccines & Immunotherapeutics 255
Human Vaccines & Immunotherapeutics Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/khvi20
Human Vaccines & Immunotherapeutics: News Eva M Riedmann
a
a
Acquisitions Editor; Landes Bioscience; Vienna, Austria Published online: 15 May 2014.
Click for updates To cite this article: Eva M Riedmann (2014) Human Vaccines & Immunotherapeutics: News, Human Vaccines & Immunotherapeutics, 10:2, 252-255, DOI: 10.4161/hv.28444 To link to this article: http://dx.doi.org/10.4161/hv.28444
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Versions of published Taylor & Francis and Routledge Open articles and Taylor & Francis and Routledge Open Select articles posted to institutional or subject repositories or any other third-party website are without warranty from Taylor & Francis of any kind, either expressed or implied, including, but not limited to, warranties of merchantability, fitness for a particular purpose, or non-infringement. Any opinions and views expressed in this article are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor & Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/terms-and-conditions It is essential that you check the license status of any given Open and Open Select article to confirm conditions of access and use.
Policy& & Profiles News, News, Policy Profiles
Human Vaccines & Immunotherapeutics 10:2, 252–255; February 2014; © 2014 Landes Bioscience
Human Vaccines & Immunotherapeutics: News
Downloaded by [University of Bristol] at 03:35 27 February 2015
Recently approved pandemic and seasonal influenza vaccines The US Food and Drug Administration (FDA) recently approved the first adjuvanted vaccine for the prevention of H5N1 influenza, commonly known as avian or bird flu. The influenza A (H5N1) monovalent vaccine, developed by GSK, is indicated for use in adults who are at increased risk of exposure to the H5N1 influenza virus. Avian influenza is an infectious disease of birds caused by certain influenza A viruses. While most avian influenza A viruses do not infect people, some viruses, such as H5N1, have caused serious illness and death in people. According to the World Health Organization (WHO), about 60% of people infected with H5N1 die. The vaccine is not intended for commercial availability, but the US Department of Health and Human Services has purchased it for inclusion in the National Stockpile for distribution by public health officials if needed. “This vaccine could be used in the event that the H5N1 avian influenza virus develops the capability to spread efficiently from human to human, resulting in the rapid spread of disease across the globe,” said Dr Karen Midthun, director of the FDA’s Center for Biologics Evaluation and Research. “Vaccines are critical to protecting public health by helping to counter the transmission of influenza disease during a pandemic.” The FDA approval was based on a trial of 4500 adults, which showed that 91% of subjects aged 18-64 years had an antibody response consistent with protection against the H5N1 virus following immunization with two doses. The vaccine was less effective in people >65 years but still protected more than two-thirds of subjects in this age group. The vaccine was found to be safe, with the most common side effects reported being infection site pain, muscle aches, headache, fatigue,
and injection site redness and swelling. The FDA advisory panel had unanimously recommended the vaccine already one year ago, but approval was delayed because the vaccine is adjuvanted with AS03. This adjuvant was also used in GSK`s H1N1 vaccine, which has been linked to the development of narcolepsy, with ~800 cases of narcolepsy developing following immunization. Another recently approved influenza vaccine is AstraZeneca’s intranasal four-strain live attenuated seasonal vaccine for children and adolescents. The European Commission (EC) has granted Marketing Authorization to Fluenz Tetra, making it the first and only intranasal tetravalent influenza vaccine available in Europe. The EC decision follows a positive opinion from the Committee for Medicinal Products for Human Use and is applicable to all 28 member states and the three European Economic Area countries of the European Union. Until recently, seasonal vaccines have contained three strains of influenza: two A viruses and one B virus. Fluenz Tetra contains an additional B strain. Over the past decade, ~25% of circulating influenza strains in Europe were influenza B strains. “Fluenz Tetra represents the next generation of influenza vaccine and we are pleased that it is now approved in Europe,” said Dr Filip Dubovsky, Vice President of Clinical Biologics Infectious Disease and Vaccines at MedImmune, AstraZeneca’s global biologics research and development arm. “The inclusion of a second influenza B strain will broaden the coverage of Fluenz Tetra and should have a valuable public health impact.” Approval of Fluenz Tetra was based on data from a pivotal paediatric study, showing that Fluenz Tetra demonstrated a safety and immunogenicity profile that was comparable to Fluenz, a trivalent live attenuated vaccine
approved in Europe. Fluenz Tetra is planned to replace the trivalent vaccine Fluenz from the 2014-15 flu season onwards. In the US, Fluenz Tetra is marketed under the trade name FluMist Quadrivalent, approved since 2012. Finally, the New England Journal of Medicine published a study on the effectiveness of the quadrivalent influenza vaccine FluLaval in preventing seasonal flu in children.1 The study was one of the pivotal clinical trials leading to the recent FDA approval of GSK´s FluLaval Quadrivalent vaccine. The randomized, controlled clincial trial included >5200 children, and was the first large-scale study conducted specifically to review the safety and effectiveness of vaccinating children with a four-strain flu vaccine. FluLaval Quadrivalent was shown to reduce influenza cases among children aged 3-8 years by 55% overall and lowered the risk of developing moderate-to-serious flu illness by 73%. “The U.S. Centers for Disease Control recommends that all children get vaccinated each flu season. This is in response to how many children require flu-related medical care, and given that as many as 20 000 U.S. children are hospitalized each year due to complications of the flu,” said Dr Leonard Friedland, Vice President, Director Scientific Affairs and Public Health, GSK Vaccines North America. “This study provides robust safety and efficacy data on FluLaval Quadrivalent, and evidence of the clinical benefit of vaccination with FluLaval Quadrivalent as demonstrated by the prevention of moderate-to-severe cases of influenza among children.” Reference 1. Jain VK, et al. N Engl J Med 2013; 369:2481-91; PMID:24328444; http://dx.doi.org/10.1056/ NEJMoa1215817
Agenus cancer vaccine extends survival of GBM patients The biotechnology company Agenus recently published results from a Phase 2 clinical study, demonstrating that >90% of patients treated with the company‘s brain
252
cancer vaccine Prophage Series G-200 were alive at six months after surgery and 30% were alive at 12 months. Median overall survival (OS) was approximately 11 months.
Human Vaccines & Immunotherapeutics
Prophage Series vaccines are individualized heat shock protein-based therapeutic cancer vaccines, manufactured using a patient’s own tumor after surgical removal.
Volume 10 Issue 2
Downloaded by [University of Bristol] at 03:35 27 February 2015
Thus, each vaccine contains the antigenic fingerprint of a patient’s particular cancer. They are designed to activate the immune system to specifically target and destroy cancer cells bearing this fingerprint. In the current multi-center,single-arm Phase 2 study, 41 patients with surgically resectable recurrent Glioblastoma multiforme (GBM) were repeatedly immunized with Prophage Series G-200 to assess the survival rate at six months. GBM is the most common and aggressive form of primary brain cancer, and patients face a poor prognosis. Trial participant had surgery to remove ≥90% of their tumors, which were then used to manufacture Prophage Series G-200. The vaccine was given to patients once weekly for four weeks, followed by biweekly injections until vaccine depletion. The vaccine showed a good safety
profile. About 90% of treated patients were alive at 6 months following surgery, and 30% were still alive at 12 months. Median OS was approximately 11 months, which compares favorably to the expected median survival for recurrent GBM patients of 3–9 months. The data were recently published in the journal Neuro-Oncology.2 “Glioblastoma tumors are often resistant to standard therapies and the extended survival observed in patients treated with Prophage Series vaccine is very promising,” said Dr Andrew Parsa from the Feinberg School of Medicine at Northwestern University, corresponding author of the study. “The next phase of development is underway with an NCI funded, large-scale, randomized trial investigating Prophage Series G-200 in combination with Avastin (bevacizumab). Avastin
is approved for the treatment of recurrent GBM and we believe there is the potential for a synergistic effect of a targeted anti-tumor immunotherapy and anti-angiogenic agent that could benefit patients.” The ongoing ALLIANCE Trial, studying a combination of Prophage Series G-200 and Avastin, is the largest brain tumor trial ever funded by the NCI and the largest vaccine study ever conducted with Avastin (previously reported in HV&I news 9-10). The study aims to advance the treatment of GBM, the most common and malignant form of brain cancer. Reference 2. Bloch O, et al. Neuro Oncol 2014; 16:274-9; PMID:24335700; http://dx.doi.org/10.1093/ neuonc/not203
Influenza vaccines prevented over 6 million flu cases in the US In a recent report, the Centers for Disease Control and Prevention (CDC) estimated influenza illnesses and hospitalizations averted by influenza vaccination in the US during the 2012–13 flu season. 3 Based on CDC surveillance data, the 2012– 13 influenza season was characterized as moderately severe. Rates of influenza-associated hospitalizations were 42 per 100 000 persons, compared to 7.7–23.4 per 100 000 during the previous three seasons. 169 influenza-associated pediatric deaths (deaths among persons 60 years of age. The data showed that PPV23 does not provide any relevant benefit against AMI in this population. Cardiovascular benefits associated with PPV23 vaccination are controversial. The study published in a recent issue of the journal Vaccine6 is the first prospective study using validated clinical data to evaluate relationships between pneumococcal vaccination and risk of myocardial infarction. It is a follow-up of the CAPAMIS study, published in 2010, which aimed to clarify the controversial effect of PPV23 in preventing communityacquired pneumonia and the possible role of pneumococcal vaccination in cardiovascular prevention.7
254
A Spanish team of researchers conducted the population-based cohort study involving >27 000 individuals over age 60, who were prospectively followed for three years (from December 2008 to December 2011). Outcomes were hospitalization for AMI, 30-day mortality from AMI, and all-cause death. Cox regression was used to evaluate the association between pneumococcal vaccination and the risk of each outcome. Study subjects were followed for a total of 76 033 person-years, of which 29 065 were for vaccinated subjects. Overall, 359 cases of AMI, 55 deaths from AMI and 2465 all-cause deaths were observed. Pneumococcal vaccination did not alter the risk of AMI, death from AMI and all-cause death in the general population of people over 60 years. Analyses focused on people with and without history of prior coronary artery disease, showed that
Human Vaccines & Immunotherapeutics
pneumococcal vaccination did not emerge effective in preventing any analyzed event. In conclusion, this new study supports that PPV23 does not provide any relevant benefit against AMI in the general population >60 years, as in primary as well as in secondary prevention, although it is underpowered to exclude a small benefit of vaccination against rare outcomes. References 6. Ochoa-Gondar O, et al. Vaccine 2014; 32:2527; PMID:24262314; http://dx.doi.org/10.1016/j. vaccine.2013.11.017 7. Vila-Corcoles A, et al. BMC Public Health 2010; 10:25; PMID:20085658; http://dx.doi. org/10.1186/1471-2458-10-25
Volume 10 Issue 2
Downloaded by [University of Bristol] at 03:35 27 February 2015
Vical initiates vaccine trials against HSV-2 and CMV The San Diego-based biotech company Vical Incorporated recently announced the inititation of two clinical trials: a Phase 1/2 study of its therapeutic vaccine for herpes simplex virus type 2 (HSV-2), and a Phase 2 study of its cytomegalovirus (CMV) vaccine for solid organ transplant (SOT) recipients. HSV-2 is a sexually transmitted virus and the leading cause of recurrent genital herpes. Worldwide, one out of every six individuals aged 15 to 49 years is chronically infected with HSV-2. Persistent infection may result in periodic virus shedding placing sexual partners at risk of infection. It also can lead to debilitating genital lesions, which significantly increase the risk of acquiring HIV-1 virus from HIVinfected sexual partners. There is no approved vaccine for HSV. Vical will test its HSV-2 DNA vaccine, formulated with the company’s proprietary adjuvant Vaxfectin, in approximatly 150 healthy HSV-2-infected adults at six key US clinical sites. The randomized double-blind, placebocontrolled trial will evaluate safety, tolerability and efficacy of the vaccine. “The initiation of this trial represents another milestone for Vical,” said Dr Larry Smith, Vice President of Vaccine Research at Vical. “Our trial is designed to demonstrate
reductions in the rate of HSV-2 that is shed from individuals with symptomatic genital herpes. A therapeutic vaccine may be the ideal approach for reducing viral shedding because of the ability to harness the immune system to control HSV-2, potentially freeing subjects from daily, lifelong antiviral drug usage. This Phase 1/2 trial is a vital step towards developing a product that not only limits viral shedding but may also reduce both symptomatic genital herpes lesions as well as virus transmission.” The other recently initiated clinical trial tests a vaccine against CMV. This herpesvirus infects more than half of all adults in the US by age 40, and is even more widespread in developing countries. Healthy people are usually protected against CMV disease, even though they may be latent carriers. Individuals with impaired immune system function, including transplant patients, are at high risk of CMV reactivation, potentially leading to severe illness or death. Vical is developing its CMV vaccine ASP0113 (formerly TransVax) in collaboration with Astellas Pharma. The Japanese biopharmaceutical company is conducting the trial under an exclusive worldwide license agreement with Vical to develop and commercialize
ASP0113. Vical is providing development, regulatory and manufacturing support. The investigational bivalent DNA vaccine ASP0113 contains plasmids encoding human CMV pp65 and gB antigens and is designed to induce both cellular and humoral immune responses. A proprietary poloxamer-based delivery system is used for formulation. The randomized, double-blind, placebocontrolled Phase 2 trial is designed to evaluate the efficacy of ASP0113 compared to placebo as measured by the incidence of CMV viremia in CMV-seronegative subjects receiving a kidney from a CMV-seropositive donor. The study, include approximately 140 SOT recipients, will also evaluate the safety of ASP0113 in this patient population. Each subject will be followed-up for one year following enrollment. “Following the initiation of our Phase 3 trial of ASP0113 in hematopoietic cell transplant (HCT) recipients in June, we are pleased to expand the ASP0113 program with this Phase 2 trial in SOT recipients,” said Dr Bernie Zeiher, Senior Vice President and Global Therapeutic Area Head of Immunology and Infectious Diseases at Astellas Pharma Global Development, Inc. “The unmet medical need to control CMV in transplant recipients remains high.”
Fingerprint sensors to track vaccination records in developing countries The US company Lumidigm (Albuquerque, NM) in partnership with Fulcrum Biometrics (San Antonio, TX) has developed multispectral imaging fingerprint sensors that are helping to keep vaccination records up-to-date and stop vaccine wastage in developing countries. Vaccine delivery in low-resource countries has often been hampered by ineffective tracking and reporting, and consequently many young children are not being vaccinated. The delivery model in many parts of Africa depends on a multitude of healthcare workers who serve very large and remote areas. Lacking or incomplete vaccination records lead to many patients being re-immunized unnecessarily, while others are simply missed and a finite supply of vaccine is wasted. In some of the most challenging geographics, vaccine wastage is estimated to be >50%. VaxTrac, supported by The Bill and Melinda
www.landesbioscience.com
Gates Foundation among others, wants to solve this problem with a biometric vaccination registry that is operated and managed in the field with low-cost mobile devices. Adult and child patients are identified in the registry with fingerprint sensors from Lumidigm. With the simple touch of a finger, returning patients can pull up their vaccination records, allowing the healthcare worker to deliver appropriate care. The biometric vaccine registry also enables real-time reporting for streamlined supply-chain management, further reducing waste. “With our VaxTrac system leveraging Lumidigm fingerprint sensors, we have been able to improve immunization tracking, which allows us to reduce waste so that we can vaccinate more people and save lives,” asserts Dr Mark Thomas, executive director of VaxTrac. “We started evaluating Lumidigm sensors
in 2012. Since the skin of children, especially young children, can be very malleable, we knew from experience that conventional biometric technologies that need a finger pressed against the device do not work. The ability that Lumidigm offers to pull fingerprint images from deeper layers produces images less susceptible to distortion and allows us to track vaccinations accurately.” The first in-country deployment of the Lumidigm fingerprint sensors was in March 2013. The units are now in Kenya, Uganda and Benin, with the largest deployment in 40 clinics throughout Zambia. Community healthcare workers are trained to use the simple, user-friendly record system, especially developed for workers with limited literacy. Expensive, specialized training for vaccine delivery in remote areas is no longer necessary with the biometric VaxTrac system.
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