Table of Contents

Volume 6, Issue 11

  November 2010

  Pages 865 - 953

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 Issue Catalogue (MARC XML)

EDITOR'S CORNER

Open Access Article

Letter from the Editor

Ronald W. Ellis and Eva Maria Riedmann
Page 865
http://dx.doi.org/10.4161/hv.6.11.14103
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NEWS, POLICY AND PROFILES

Open Access Article

News

Eva Maria Riedmann
Pages 866 - 869
http://dx.doi.org/10.4161/hv.6.11.14104
Abstract | PDF

New vaccine extends survival for glioblastoma patients

Novartis develops first potential broad-coverage MenB vaccine

Anti-vaccine movement threatens America’s children

Successful Phase II for therapeutic CMV vaccine

Plant-based flu vaccine moves to human tests

European Malaria Vaccine Development Association

Low-cost cervical cancer vaccine ready for human trials

Pneumococcal vaccine opens niche for multi-drug-resistant strain

Mandatory flu vaccine for healthcare workers recommended

 

Open Access Article

Questions for Biotechs: BiondVax Pharmaceuticals Ltd.

Tamar Ben-Yedidia
Pages 870 - 871
http://dx.doi.org/10.4161/hv.6.11.14105
PDF




PORTRAIT OF A LEADING VACCINOLOGIST

Open Access Article

Bacterial vaccine discovery: From “brute force” to high selectivity

Guido Grandi
Pages 872 - 875
http://dx.doi.org/10.4161/hv.6.11.14216
PDF




MEETING REPORT

Open Access Article

The global pertussis initiative: Meeting report from the regional Latin America meeting, Costa Rica, 5-6 December, 2008

Rolando Ulloa-Gutierrez, Daniela Hozbor, Maria L. Avila-Aguero, Jaime Caro, Carl-Heinz Wirsing von König, Tina Tan and Stanley Plotkin
Pages 876 - 880
http://dx.doi.org/10.4161/hv.6.11.13077
Abstract | PDF

Pertussis remains endemic across the world, with an estimated 279,000 deaths in 2002, the majority in infants under 1 year of age. Worldwide epidemiologic data indicates increasing infection rates in older children and adults, which act as a source of infection to young infants. The Global Pertussis Initiative (GPI) is an expert scientific forum, which has published consensus recommendations for the monitoring, prevention, and treatment of the disease. This paper reports the proceedings of a regional meeting, held in Costa Rica in December 2008. The meeting gathered information on regional epidemiological, diagnostic capabilities and the ability to introduce GPI recommended vaccine strategies in Latin America. The capacity of Latin American countries to conduct vaccination programs is high and there is considerable government support. Whole-cell pertussis vaccines are used across Latin America, which appear to be quite effective. A 4-dose schedule is typically used (2, 4, 6, and 18 months), and a booster given at 4 to 6 years of age, with coverage often above 90%, but with regions of low coverage due to political and geographical difficulties. Adequate surveillance is lacking in many countries, giving insufficient data to guide vaccination policy. Improvements are being made, with countries such as Costa Rica, Panama, and Argentina introducing polymerase chain reaction (PCR) diagnosis. Those countries that do not currently use a preschool booster should launch one. Implementing vaccination programs in adolescents and/or adults to reduce exposure to infants would be beneficial and possible in most countries, given their current infrastructure.




SHORT REPORT

Open Access Article

Persistence of immune responses after a single dose of Novartis meningococcal serogroup A, C, W-135 and Y CRM-197 conjugate vaccine (Menveo®) or Menactra® among healthy adolescents

Christopher J. Gill, Roger Baxter, Alessandra Anemona, Giuseppe Ciavarro and Peter Dull
Pages 881 - 887
http://dx.doi.org/10.4161/hv.6.11.12849
Abstract | PDF

The persistence of human bactericidal activity (hSBA) responses in adolescents was assessed 22 months after vaccination with one dose of Menveo® (MenACWY-CRM; Novartis) or Menactra® (MCV4) (sanofi pasteur). The proportion of subjects with hSBA titers ≥8 was significantly higher among recipients of MenACWY-CRM than MCV4 for serogroups A, W-135 and Y.




RESEARCH PAPERS

Open Access Article

Immunogenicity and safety of a novel AS03A-adjuvanted H1N1 2009 pandemic influenza vaccine in adults in Japan

Hideyuki Ikematsu, Hideaki Nagai, Masahiro Kawashima, Yasunobu Kawakami, Kazuyoshi Tenjinbaru, Atsushi Maeda, Ping Li, Paul Gillard and François Roman
Pages 888 - 893
http://dx.doi.org/10.4161/hv.6.11.12851
Abstract | PDF

We are grateful to the New York Medical College, New York for providing the vaccine virus strain and to the National Institute for Biological Standards and Control (NIBSC, UK) and the Therapeutic Goods Administration (TGA) from the Australian Government for providing the reference standards. The authors are indebted to the participating study volunteers, clinicians, nurses and laboratory technicians at the study sites as well as to the sponsor’s project staff for their support and contributions throughout the study. We are grateful to all teams of GSK Biologicals for their contribution to this study, especially Kazunori Yagi, Maki Matsuzaki, Kayoko Endo, Kenji Ishizuka, Shinobu Tamura, Hiroshi Tamura for clinical study management and site monitoring, Karl Walravens and Roger Bernhard from the clinical and serological laboratory teams, Liliana Manciu for preparation of the study protocol and related study documentation, Koen Ceulemans for global study management, Dorothy Slavin (Clinical Safety Representative), Edith Lépine for project management, and David Vaughn for project direction. The authors thank Avishek Pal (GlaxoSmithKline Biologicals) for medical writing and Dr Antoine Minne (Keyrus Biopharma) and Dr. Wendy Van Doorslaer (XPE Pharma & Science) for editorial assistance and manuscript coordination.

Open Access Article

Concomitant administration of zoster and pneumococcal vaccines in adults ≥60 years old

C. Raina MacIntyre, Tony Egerton, Malcolm McCaughey, Janie Parrino, Bernadette V. Campbell, Shu-Chih Su, Marco F. Pagnoni, Jon E. Stek, Jin Xu, Paula W. Annunziato, Ivan S. F. Chan and Jeffrey L. Silber
Pages 894 - 902
http://dx.doi.org/10.4161/hv.6.11.12852
Abstract | PDF

This study evaluated safety & immunogenicity of ZOSTAVAX® (zoster vaccine: ZV) administered concomitantly versus nonconcomitantly with PNEUMOVAX® 23 (pneumococcal vaccine: PPV23). This randomized, double-blind, placebo-controlled study enrolled 473 subjects ≥60 years old in 1:1 ratio to receive ZV & PPV23 concomitantly (Day 1) or nonconcomitantly (PPV23 Day 1, ZV Week 4). Blood samples obtained for pneumococcal polysaccharide (PnPs) antibody (Ab) testing by enzyme-linked immunosorbent assay (ELISA) and varicella-zoster virus (VZV) Ab testing by glycoprotein ELISA. Subjects followed for adverse experiences (AEs) for 28 days postvaccination. Mean baseline VZV geometric mean titers (GMT) in nonconcomitant group were lower than concomitant group. Four weeks postvaccination with ZV, VZV Ab response in concomitant group was not similar to nonconcomitant group; estimated VZV GMT ratio [concomitant/nonconcomitant] was 0.70 (95% CI, 0.61-0.80). VZV Ab response was acceptable in concomitant group; estimated geometric mean foldrise (GMFR) from baseline was 1.9 (95% CI, 1.7-2.1). PnPs serotype-specific Ab responses were similar in both groups. All 6 reported serious AEs were deemed not related to study vaccine. Postvaccination of ZV, incidence of injection-site AEs was similar in both groups; clinical AEs were numerically but not significantly higher in nonconcomitant group. In summary, VZV GMT Ab response induced by ZV administered concomitantly with PPV23 was inferior to that induced nonconcomitantly. These results indicate that, to avoid a potential decrease in ZV immunogenicity, ZV & PPV23 should not be given concomitantly. Concomitant administration did not affect response to PPV23 serotypes tested. When administered concomitantly, ZV & PPV23 vaccines were generally well tolerated.

Open Access Article

Evaluation of vaccination results in high-risk patients included in hepatitis B vaccination program

Sükran Köse, Melda Türken, Gülsün Cavdar, Bengü Tatar and Süheyla Serin Senger
Pages 903 - 905
http://dx.doi.org/10.4161/hv.6.11.12918
Abstract | PDF

Hepatitis B infection is one of the infectious diseases quite common in Turkey and around the world. Hepatitis B virus infection is a significant health problem which may cause chronic hepatitis, cirrhosis and hepatocellular carcinoma. With the introduction of Hepatitis B vaccine, a significant progress has been made in the prevention of HBV infections. The purpose of the study was to evaluate the characteristics of the individuals included in the risk group who admitted to our vaccination clinic, as well as their immune responses following the vaccination. Among the patients admitted to the vaccination clinic of our hospital between January 2003-December 2005 and that were included in the risk group (patients who have family members with chronic Hepatitis B infection, healthcare workers, hemodialysis patients etc.), those who were included in the vaccination program by examining the results of HBs Ag, anti-HBc and anti-HBs were evaluated in terms of their characteristics (age, gender, smoking etc.) and results of Anti-HBs score. A total of 958 people were included in the vaccination program. Upon evaluation in terms of risk factors, presence of patients with chronic hepatitis B infection in the family was found to be 80.6%(772/958), being healthcare worker was 9.2%(88/958), HCV positivity and chronic liver disease was 3.0%(29/958), being a hemodialysis patient was 2.8%(27/958), and being an oncology patient was 2.1%(20/958). Post-vaccination immune response could be evaluated in 69.8% (669/958) of patients and no responsiveness to vaccine was detected only in 8.1%(54/669) of them. Of the non-responders, 64.8% (35/54) were hemodialysis and oncology patients. Anti-HBs positivity rate following hepatitis B vaccination program was found compatible with the results of previous studies. With this vaccine of considerably high effectiveness, immunization of the entire community including primarily the risk groups should be targeted.

Open Access Article

Concomitant or sequential administration of live attenuated Japanese encephalitis chimeric virus vaccine and yellow fever 17D vaccine: Randomized double-blind phase II evaluation of safety and immunogenicity

Peter E Nasveld, Joanne Marjason, Sonya Bennett, John Aaskov, Suzanne Elliott, Karen McCarthy, Niranjan Kanesa-thasan, Emmanuel Feroldi and Mark Reid
Pages 906 - 914
http://dx.doi.org/10.4161/hv.6.11.12854
Abstract | PDF

A randomized, double-blind, study was conducted to evaluate the safety, tolerability and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) co-administered with live attenuated yellow fever vaccine (YF-17D strain; Stamaril®, Sanofi Pasteur) or administered successively. Participants (n = 108) were randomized to receive: YF followed by JE-CV 30 days later, JE followed by YF 30 days later, or the co-administration of JE and YF followed or preceded by placebo 30 days later or earlier. Placebo was used in a double-dummy fashion to ensure masking. Neutralizing antibody titers against JE-CV, YF-17D and selected wild-type JE strains was determined using a 50% serum-dilution plaque reduction neutralization test. Seroconversion was defined as the appearance of a neutralizing antibody titer above the assay cut-off post-immunization when not present pre-injection at day 0, or a least a four-fold rise in neutralizing antibody titer measured before the pre-injection day 0 and later post vaccination samples. There were no serious adverse events. Most adverse events (AEs) after JE vaccination were mild to moderate in intensity, and similar to those reported following YF vaccination. Seroconversion to JE-CV was 100% and 91% in the JE/YF and YF/JE sequential vaccination groups, respectively, compared with 96% in the co-administration group. All participants seroconverted to YF vaccine and retained neutralizing titers above the assay cut-off at month six. Neutralizing antibodies against JE vaccine were detected in 82-100% of participants at month six. These results suggest that both vaccines may be successfully co-administered simultaneously or 30 days apart.




COMMENTARIES

Open Access Article

Assessment of HPV vaccines: From the burden of disease to the Health Technology Assessment approach

Giuseppe La Torre
Pages 915 - 917
http://dx.doi.org/10.4161/hv.6.11.12853
PDF

Open Access Article

Why it is still important that countries know the burden of pneumococcal disease

Rosa Prato, Silvio Tafuri, Francesca Fortunato and Domenico Martinelli
Pages 918 - 921
http://dx.doi.org/10.4161/hv.6.11.13352
Abstract | PDF

Pneumococcal diseases are a major public health problem worldwide. WHO estimates about 1.6 million of annual deaths, mostly in infants, elderly and immunocompromised individuals. Data on the burden of pneumococcal diseases are still limited but information on serotypes circulation and epidemiological pattern of diseases are essential to assess the impact of old and new vaccines. The 23-valent pneumococcal polysaccharide vaccine is recommended in the elderly in many industrialized countries. The 7-valent polysaccharide-protein conjugate vaccine is introduced into routine infant immunization programs of several countries; it is modifying the epidemiology of invasive pneumococcal diseases (IPD) in the population, including adults of all ages. The 10-valent pneumococcal conjugate vaccine is licensed for active immunization of infants and children from 6 weeks up to 2 years of age but it does not contain the emergent 19A serotype. The 13-valent pneumococcal conjugate vaccine is an evolution of the 7-valent and currently addresses the overall need for a broader serotypes coverage. Vaccine manufacturers must continue to further develop pneumococcal vaccines covering the majority of the circulating serotypes in all age groups. Vaccination appears to be the only public health action that could reduce the impact of IPD.

Open Access Article

Marking November 12, 2010 – World Pneumonia Day: Where are we, where are vaccines?

Ron Dagan, Ciro A. de Quadros, Javier Garau, Keith P. Klugman, Najwa Khuri-Bulos, Orin Levine, Samba Sow and Yonghong Yang
Pages 922 - 925
http://dx.doi.org/10.4161/hv.6.11.13599
Abstract | PDF

Infectious diseases such as smallpox, pneumonia, rotavirus, malaria and measles have inflicted untold pain, suffering and death on the human population. The fingerprints of these deadly diseases can be found across the pages of history. The harrowing effects of pneumonia on the human body were described by Hippocrates as early as 460 B.C.;¹ smallpox scarring can be found on Egyptian mummies dating back more than 3,000 years ago;² and the Persian philosopher and physician Rhazes detailed the devastation of measles in the 10 century A.D.³ Without the benefits of modern medical interventions, our ancestors had little to no defense against infectious disease, and mortality rates were staggering. In 1531, for example, measles was responsible for the death of half the population of Honduras.⁴ Furthermore, some historical estimates indicate case fatality rates as high as 90 percent during smallpox epidemics among Native American populations in the early part of the 15th century.⁵ Yet as science advanced, humanity developed defenses against infectious disease in the form of lifesaving interventions, including vaccines, medical products (e.g., bed nets), therapeutics, and behavioral interventions.⁶ Across the developed world, these interventions quickly turned the tide against infectious disease. In the United States, infectious disease mortality declined 95 percent during the first 8 decades of the 20th century, from 797 deaths per 100,000 in 1900 to 36 deaths per 100,000 in 1980.⁷ The success of vaccination programs in the United States and Europe ushered in the 20th-century the concept of "disease eradication"—the idea that a specific disease could be eliminated from the planet. In 1977, after a decade-long campaign involving 33 nations, smallpox was eradicated worldwide—approximately ten years after it had been eradicated from the United States and the rest of the Western Hemisphere.⁸ But for millions living in the world’s poor and developing countries, it is as if these live-saving interventions were never developed. The World Bank defines developing countries as those making less than US $11,905 gross national income per capita per year. People living in developing countries make up more than 80 percent of the world’s population.⁹ A child born in a developing country faces many of the same risks her ancestors did 1,000 years ago. She is 237 times more likely to die of Hib disease than a child born to parents living in a high-income country.¹⁰ She’s also 118 times more likely to die from rotavirus diarrhea,¹¹ 89 times more likely to die from pneumococcal disease,¹⁰ 57 times more likely to die from HIV/AIDS,12 and 29 times more likely to die from tuberculosis.¹² For such children, life-saving medical interventions are few and far between. That is why child mortality rates in the developing world remain as high as 60 times those in developed countries,¹³ and life expectancies are shorter by almost a quarter century.¹⁴




SPECIAL FOCUS REVIEWS

Open Access Article

Virus-like particle based vaccines for Alzheimer disease

Bryce Chackerian
Pages 926 - 930
http://dx.doi.org/10.4161/hv.6.11.12655
Abstract | PDF

Vaccines targeting the amyloid-β (Aβ) peptide have promise as immunotherapies for the treatment of Alzheimer disease (AD). Human trials of a first generation Aβ vaccine highlighted the need for a vaccine strategy that could consistently induce high-titer antibodies against Aβ without also inducing inflammatory auto-reactive T-cell responses. in this review, I will describe the use of virus-like particle (vLP) based vaccines against Aβ that can potentially satisfy these demands. vLPs can serve as highly multivalent platforms for the display of diverse antigens on their surfaces. vLP display markedly increases the immunogenicity of antigens, including self-antigens. vLP- based immunogens targeting Ab have been developed by several different groups, and have demonstrated effectiveness in animal models of AD. One vLP-based candidate vaccine for AD, CAD106, developed by Cytos Biotechnology and Novartis Pharmaceuticals, is currently in human clinical trials.

Open Access Article

Anti-tau oligomers passive vaccination for the treatment of Alzheimer disease

Rakez Kayed
Pages 931 - 935
http://dx.doi.org/10.4161/hv.6.11.12689
Abstract | PDF

The aggregation and accumulation of the microtubule-associated protein (Tau) is a pathological hallmark of Alzheimer’s disease (AD) and many neurodegenerative diseases. Despite the poor correlation between neurofirillary tangles (NFTs) and disease progression, and evidence showing, that neuronal loss in AD actually precedes NFTs formation research until recently focused on them and other large meta-stable inclusions composed of aggregated hyperphosphorylated tau protein. Lately, the significance and toxicity of NFTs has been challenged and new aggregated tau entity has emerged as the true pathogenic species in tauopathies and a possible mediator of Aβ toxicity in AD. Tau intermediate aggregate (tau oligomers; aggregates of an intermediate that is between monomers and NFTs in size) can cause neurodegeneration and memory impairment in the absence of Aβ. This exciting body of evidence includes results from human brain samples, transgenic mouse and cell-based studies. Despite extensive efforts to develop a safe and efficacious vaccine for AD using Aβ peptide as an immunogen in active vaccination approaches or anti Aβ antibodies for passive vaccination, success has been modest. Nonetheless, these studies have produced a wealth of fundamental knowledge that has potential to application to the development of a tau-based immunotherapy. Herein, I discuss the evidence supporting the critical role of tau oligomers in AD, the potential and challenges for targeting them by immunotherapy as a novel approach for AD treatment.

Open Access Article

Simplified β-amyloid peptides for safer Alzheimer’s vaccines development

Antonio Verdoliva, Vincenzo Rivieccio and Maria Rossi
Pages 936 - 947
http://dx.doi.org/10.4161/hv.6.11.13034
Abstract | PDF

Over the past few years, new ways of fighting Alzheimer’s disease have emerged based on stimulating the immunitary defence system of the patients. To avoid toxicity and autoimmune response related to the Aβ[1-42] peptide immunotherapy, in the last decade a large number of works aimed at identifying new classes of safe Aβ derivatives by modifying the full length β-amyloid form. In strict agreement with the purposes of the sequence-simplification technology, Aβ[1-16], Aβ[13-28] and Aβ[25-42] fragments were selected in order to retain the major immunogenic sites of the Aβ[1-42] peptide, and corresponding simplified forms were designed and synthesized. All glycinated Aβ derivatives showed immunogenic and antigenic properties similar to the parent Aβ[1-42] peptide, and raised antibodies were all able to cross-recognize both Aβ[1-42] and Aβ[1-40] synthetic structures. All Aβ simplified forms showed reduced fibrillogenic and inflammatory properties. In particular, the Aβ[13-28]+G form failed to induce IFN-γ production thus suggesting that this molecule could represent a good candidate for potentially safer AD vaccine therapy.

Open Access Article

AFFITOME® technology in neurodegenerative diseases: The doubling advantage

Achim Schneeberger, Markus Mandler, Frank Mattner and Walter Schmidt
Pages 948 - 952
http://dx.doi.org/10.4161/hv.6.11.13217
Abstract | PDF

Neurodegenerative diseases are still an area of unmet medical need. This is in contrast to our increasing knowledge on their pathology (e.g., Alzheimer’s- (AD), Parkinson’s (PD) disease). They are driven by the cerebral accumulation and aggregation of specific proteins (e.g., β-amyloid and hyperphosphorylated tau in the case of AD) in defined brain regions and, as a consequence, death of neurons. Accordingly, removal of given protein aggregates is expected to modify the course of the respective neurodegenerative disease. This has been convincingly demonstrated in animal models of human diseases. However, not every technology that can be used and proves successful in animal models can be translated to the human situation. As highlighted by recent progress in the field of AD research, specific immunotherapy is a viable option in this regard. Given the fact that the aggregates are composed of self-proteins, immunotherapeutic approaches have to consider the issue of potential autoimmunity. This is especially true in case of vaccines. An innovative solution to this problem is offered by the so called AFFITOME® technology, which relies on the use of “doubles” of native molecules, functionally mimotopes or AFFITOPES® if identified by AFFiRiS, as the antigenic vaccine component.




LETTER

Open Access Article

Effectiveness of Lanzhou lamb rotavirus vaccine against hospitalized gastroenteritis: Further analysis and update

Chuanxi Fu
Page 953
http://dx.doi.org/10.4161/hv.6.11.12847
PDF