Table of Contents

Volume 7, Issue 11

  November 2011

  Pages 1113 - 1244

Special Focus: Neglected Vaccines - Developing World

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 Issue Catalogue (MARC XML)

EDITOR'S CORNER

Open Access Article

Letter from the Editor

Ronald W. Ellis and Eva M. Riedmann
Page 1113
http://dx.doi.org/10.4161/hv.7.11.18625
Full Text | PDF




NEWS, POLICY AND PROFILES

Open Access Article

News

Eva M. Riedmann
Pages 1114 - 1117
http://dx.doi.org/10.4161/hv.7.11.18626
Abstract | Full Text | PDF

Early-stage HIV vaccine is broadly immunogenic in clinical trial
HPV vaccine: Two shots may be as good as three
New mosquito-based malaria vaccine
Intradermal influenza vaccine now available in the US
Positive Phase 1 data for NovaDigm’s cross-kingdom vaccine NDV-3
One in ten parents do not follow recommended childhood vaccine schedule
Novel Alzheimer vaccine targets amyloid delivery
Computer model could help plan vaccine supply chain




RESEARCH PAPERS

Open Access Article

Distribution of rotavirus genotypes causing nosocomial and community-acquired acute gastroenteritis at The Children's Hospital of Philadelphia in the new rotavirus vaccine era

H Fred Clark, Diane Lawley, Daniel DiStefano, Jelle Matthijnssens and Mark J. DiNubile
Pages 1118 - 1123
http://dx.doi.org/10.4161/hv.7.11.17820
Abstract | PDF

Background: Introduction of rotavirus vaccines in the United States beginning in 2006 led to a rapid decline in the frequency of acute rotavirus gastroenteritis necessitating medical attention. We examined whether serotype replacement was occurring as a result of vaccine use. Methods: Children with gastroenteritis presenting to CHOP have been tested for rotavirus antigen in the stool. Commencing with the 1999-2000 season, positive specimens were genotyped to establish the G (VP7) and P (VP4) type. Results: In 2009-2010, 4 hospital-acquired and 18 community-acquired cases of rotavirus gastroenteritis were identified at CHOP. For the third consecutive full season since the introduction of rotavirus vaccines, the proportion of annual G3 cases was higher than in the prevaccine era. Although G3 strains caused 50% of the community cases in 2009-10, the absolute number of G3 cases actually dropped from 15 in 2007-08 to 8 and 9 in the 2008-09 and 2009-10 seasons, respectively. P[8] accounted for >90% of cases seen at CHOP in each of the last 3 seasons, including 20/22 (91%) cases during the 2009-10 season. Conclusions: Findings to date provide suggestive but still inconclusive evidence for vaccine-driven serotype replacement. Given the increased proportion of G3 cases in the new vaccine era despite the overall marked reduction in rotavirus gastroenteritis, continued surveillance is prudent.

Open Access Article

Relationship of therapeutic cancer vaccine development to population disease burden and five-year survival

Elias J. Dayoub and Matthew M. Davis
Pages 1124 - 1129
http://dx.doi.org/10.4161/hv.7.11.17837
Abstract | PDF

In the United States, therapeutic vaccines may provide considerable benefit to cancer patients.  Yet, there has been no assessment of whether vaccines currently in the research and development pipeline reflect the burden of disease and current survival patterns for different malignancies.  The authors used data from the National Cancer Institute, Surveillance Epidemiology and End Results (SEER) database, and clinicaltrials.gov registry to characterize the vaccine development pipeline with respect to 5 measures of disease burden and treatment effectiveness for cancer: annual incidence, annual mortality, five-year survival rate, recent change in five-year survival (1999-2006 vs 1990-1992), and five-year mortality estimate (=annual incidence*[1 - 5-yr survival rate]).  In 2011, the authors identified 231 active clinical trials for therapeutic cancer vaccines.  Of these trials, 81 vaccines are currently in Phase I, 140 in Phase II, and 10 vaccines in Phase III.  Vaccine trials for melanoma are most common (n=40), followed by breast cancer (34), lung cancer (30), and prostate cancer (22).  Correlation analyses revealed that only annual cancer incidence is significantly associated with current therapeutic cancer vaccine trial activity (r=.60; p=.003).  Annual mortality, 5-year survival rate and 5-year mortality estimates were not associated with vaccine trial activity.  The authors conclude that therapeutic cancer vaccine clinical trials correspond with disease incidence in the U.S., but not with measures of mortality and survival that reflect the effectiveness of currently available treatment modalities.  Future development of therapeutic vaccines for cancer may benefit patients more if there is stronger complementarity with other therapeutic options.

Open Access Article

Safety and tolerability of zoster vaccine in adults ≥60 years old

Alexander V. Murray, Keith S. Reisinger, Boris Kerzner, Jon E. Stek, Timothy A. Sausser, Jin Xu, William W. Wang, Ivan S.F. Chan, Paula W. Annunziato and Janie Parrino
Pages 1130 - 1136
http://dx.doi.org/10.4161/hv.7.11.17982
Abstract | PDF

Objective

To evaluate the general safety of zoster vaccine (ZV) in adults ≥60 years old.

Patients/Methods

Subjects were enrolled in a 1:1 ratio to receive 1 dose of ZV or placebo. Subjects were followed for serious adverse experiences (SAEs) for 42 days (primary follow-up period) and 182 days (secondary follow-up period) postvaccination. Relative-risks (ZV/placebo) for SAEs during both safety periods were calculated. Study period: 17-Sep‑2007 to 09-Jan-2009.

Results

Overall, 5,983 subjects received ZV and 5,997 received placebo. Within the primary 42-day follow-up period, 84 ZV subjects and 67 placebo subjects reported SAEs. The estimated risk of SAEs within 42 days was 1.41% for ZV versus 1.12% for placebo, with a relative-risk of 1.26 (95% CI 0.91,1.73); indicating no statistically significant difference between groups, meeting the pre-specified success criterion. During the 182-day follow-up period, 340 ZV subjects and 300 placebo subjects reported SAEs. The estimated risk of SAEs within 182 days was 5.68% for ZV versus 5.01% for placebo, with a relative-risk of 1.13 (95% CI 0.98,1.32), indicating no statistically significant difference between groups. Two subjects in the ZV group reported SAEs deemed by the investigator to be vaccine-related (uveitis and sciatica; onset Day 5 and 4, respectively). One subject in the placebo group reported a SAE deemed by the investigator to be vaccine-related (lumbar radiculopathy; onset Day 51). There were 24 fatal SAEs in the ZV group and 17 in the placebo group (relative risk = 1.41; CI: 0.77, 2.60); 6 and 5, respectively, with SAE onset during the primary 42-day follow-up period.  No deaths were deemed vaccine-related.

Conclusions

ZV and placebo groups had similar safety profiles in terms of SAEs during the primary (Day 1 to 42) and secondary (Day 1 to 182) follow-up periods.

Open Access Article

Immunogenicity, reactogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Mexican infants

Guillermo M. Ruiz-Palacios, M. Lourdes Guerrero, Lorena Hernández-Delgado, Antonio Lavalle-Villalobos, Abigail Casas-Muñoz, Yolanda Cervantes-Apolinar, Marta Moreira and Lode Schuerman
Pages 1137 - 1145
http://dx.doi.org/10.4161/hv.7.11.17984
Abstract | PDF

The immunogenicity and safety of the 10-valent pneumococcal conjugate vaccine, PHiD-CV, have been documented in European and Asian studies. In this open study conducted in Mexico (NCT00489554), 230 healthy infants received three doses of PHiD-CV and DTPa-HBV-IPV/Hib vaccines at 2, 4 and 6 months of age and two doses of oral human rotavirus vaccine at 2 and 4 months. Serotype-specific pneumococcal responses and opsonophagocytic activity (OPA) were measured one month post-dose 3. PHiD-CV’s primary vaccination course was highly immunogenic against each of the 10 pneumococcal vaccine serotypes and carrier protein D. Antibody responses against pneumococcal serotypes and protein D were generally higher in Mexican infants compared with European antibody responses, and functional OPA responses were also higher or in the same range. The most frequent solicited local symptom was pain, with high but similar incidences of grade 3 pain reported at both injection sites (up to 15% of all doses). PHiD-CV was well tolerated, with no serious adverse events considered as causally related to vaccination. Most solicited symptoms were mild and there was no increase in incidence of solicited symptoms with successive vaccine doses.

Open Access Article

Rural parents' vaccination-related attitudes and intention to vaccinate middle and high school children against influenza following educational influenza vaccination intervention

Jessica M. Sales, Julia E. Painter, Karen Pazol, Lisa M. Gargano, Walter Orenstein, James M. Hughes and Ralph J. DiClemente
Pages 1146 - 1152
http://dx.doi.org/10.4161/hv.7.11.17891
Abstract | PDF

Objective: This study examined changes in parental influenza vaccination attitudes and intentions after participating in school-based educational influenza vaccination intervention. Methods: Participants were drawn from three counties participating in a school-based influenza vaccination intervention in rural Georgia (baseline N=324; follow-up N=327). Data were collected pre- and post-intervention from phone surveys with parents’ with children attending middle- and high-school. Attitudes, beliefs, vaccination history, and intention to vaccinate were assessed.  Results:  Parents who participated in the intervention conditions reported significantly higher influenza vaccination rates in their adolescents, relative to a control group, as well as increased vaccination rates post-intervention participation relative to their baseline rates. Intervention participants reported greater intention to have their adolescent vaccinated in the coming year compared to control parents.  Significant differences were observed post intervention in perceived barriers and benefits of vaccination. Conclusions: These findings suggest that a school-delivered educational influenza vaccination intervention targeting parents and teens may influence influenza vaccination in rural communities. Future influenza vaccination efforts geared toward the parents of rural middle- and high-school students may benefit from addressing barriers and benefits of influenza vaccination.




COMMENTARIES

Open Access Article

H. pylori vaccines: Why we still don't have any

Songhua Zhang, Leonard Moise and Steven F. Moss
Pages 1153 - 1157
http://dx.doi.org/10.4161/hv.7.11.17655
Abstract | Full Text | PDF

Helicobacter pylori was appreciated as the major cause of peptic ulcers about 30 years ago and the most significant etiological agent in gastric cancer in the mid-1990s. Since that time, progress in the development of a preventive or therapeutic H. pylori vaccine has been relatively slow. The impediments to rapid advances in the field include a luke-warm enthusiasm among clinicians, research scientists, and public health authorities concerning the need for a vaccine, rudimentary understanding of the correlates of gastric immunity to H. pylori and of gastric mucosal immunology in general, the geographical heterogeneity of the H. pylori genome and insufficient pharmaceutical industry support. Recent enhancements in our understanding of the gastric immune response together with advances in H. pylori genomics now provide the potential to accelerate progress in H. pylori vaccine development. Whether an H. pylori vaccine becomes a reality will likely depend upon our ability to appropriately target the populations at highest risk of the adverse sequelae of infection.

Open Access Article

Hemophilus influenzae type b (Hib) vaccine: An effective control strategy in India

Ramesh Verma, Pardeep Khanna, Suraj Chawla, Mohan Bairwa, Shankar Prinja and Meena Rajput
Pages 1158 - 1160
http://dx.doi.org/10.4161/hv.7.11.17683
Abstract | PDF

Hemophilus influenzae type b (Hib) is an encapsulated, non-motile and non-spore-forming Gram-negative coccobacillus which causes severe pneumonia, meningitis and other life threatening illnesses. Hib disease affects almost exclusively (95%) children aged less than 5 y throughout the world. The mean age of onset is 6–24 mo after which it declines gradually until age 5 y. The World Health Organization (WHO) estimates that Hib is responsible for 3 million cases of serious illnesses and approximately 386,000 deaths worldwide each year in children aged under 5 y. In the latest position paper on Hib vaccine, WHO recommended the inclusion of Hib conjugate vaccines in all routine infant immunization programs without waiting for local disease-burden data. The WHO and the Global Alliance for Vaccine Immunization (GAVI) have been working to expand supplies of Hib vaccine, reduce vaccine cost, and assist especially low-income countries with vaccine introduction. Hib vaccine is safe, highly effective and readily available in the market. Hib vaccine has been shown to be > 95% efficacious in diverse populations around the world. Globally, hundreds of millions of doses of Hib vaccine have been administered in the last 2 decades. More than 160 countries are using Hib vaccine in national immunization programmes and around 25 countries planning to introduce. Hib vaccination fits into the India’s national immunization schedule.

Open Access Article

A novel adjuvant Ling Zhi-8 for cancer DNA vaccines

Ching-Liang Chu, Dz-Chi Chen and Chi-Chen Lin
Pages 1161 - 1164
http://dx.doi.org/10.4161/hv.7.11.17753
Abstract | PDF

DNA vaccines have a wide range of applications, with several potential advantages compared to other vaccine technologies for diseases. No DNA vaccine has yet been licensed in humans; however, a lot of effort has been made to enhance their potential as human vaccines and therapeutics. Finding an effective adjuvant is a strategy to improve the efficacy of DNA vaccines. We recently identified a fungal immunomodulatory protein Ling Zhi-8 (LZ-8) with stimulatory activity on dendritic cells (DCs) that significantly increases the efficacy of a cancer DNA vaccine in a preclinical tumor model, suggesting that LZ-8 may be a good candidate adjuvant for vaccine development. Here we discuss the possibility for applying LZ-8 to a cancer DNA vaccine for humans.

Open Access Article

Candida vaccines development from point view of US patent application

Shyh-Jen Wang
Pages 1165 - 1171
http://dx.doi.org/10.4161/hv.7.11.17821
Abstract | PDF

Candidiasis is the fourth most common bloodstream infection in hospitalized patients in the United States. Moreover, the mortality rate from Candida infections remains high, even after treatment with antifungal therapy. Vaccination would be a promising strategy for prevention of invasive fungal infections. In order to examine the main trends in anticandidal vaccine patenting activity, we conducted an analysis for anticandidal vaccine patents. We find 190 issued patent and 940 patent application documents containing the keywords Candida and vaccine within claims in the USA. Candida vaccines development, as evidenced by the numbers of issued patents, has decreased since the year 2002. Furthermore, the number of patent applications in Candida vaccines may indicate the strength of engaged resources were also in the status of stagnation during 2005-2007 and even a decline in 2008. Academic and nonprofit research institutions not only account for a large share of Candida vaccines patents but also apply for patents continually. Based on this analysis, the strength of Candida vaccines resources seems to remain stagnant in recent years due to patent prosecution or technical barrier in the filed of Candida vaccines. Therefore, we consider that Candida vaccines technology to still be under development and the researchers are still looking for scientific breakthrough in the filed.




SPECIAL FOCUS REVIEWS

Open Access Article

Advances and hurdles on the way toward a leprosy vaccine

Malcolm S. Duthie, Thomas P. Gillis and Steven G. Reed
Pages 1172 - 1183
http://dx.doi.org/10.4161/hv.7.11.16848
Abstract | PDF

Prevalence rates for leprosy have declined sharply over the past 20 y, with this decline generally attributed to the WHO multi-drug therapy (MDT) campaign to provide free-of-charge treatment to all diagnosed leprosy patients. The success of this program appears to have reached its nadir, however, as evidenced by the stalled decreases in both global prevalence and new case detection rates of leprosy. Mass BCG vaccination for the prevention of tuberculosis (TB) at national levels has had a positive effect on leprosy decline and is often overlooked as an important factor in current leprosy control programs. Because BCG provides incomplete protection against both TB and leprosy, newer more effective TB vaccines are being developed. The impact that application of these vaccines will have on current leprosy control programs is unclear. In this review, we assess the need for vaccines within leprosy control programs. We summarize and discuss leprosy vaccine strategies that have been deployed previously and discuss those strategies that are currently being developed to augment recent breakthroughs in leprosy control.

Open Access Article

Advances and challenges towards a vaccine against Chagas disease

Israel Quijano-Hernandez and Eric Dumonteil
Pages 1184 - 1191
http://dx.doi.org/10.4161/hv.7.11.17016
Abstract | PDF

Chagas disease is major public health problem, affecting nearly 10 million people, characterized by cardiac alterations leading to congestive heart failure and death of 20-40% of the patients infected with Trypanosoma cruzi, the protozoan parasite responsible for the disease. A vaccine would be key to improve disease control and we review here the recent advances and challenges of a T. cruzi vaccine. There is a growing consensus that a protective immune response requires the activation of a Th1 immune profile, with the stimulation of CD8⁺ T cells. Several vacines types, including recombinant proteins, DNA and viral vectors, as well as heterologous prime-boost combinations, have been found immunogenic and protective in mouse models, providing proof-of-concept data on the feasibility of a preventive or therapeutic vaccine to control a T. cruzi infection. However, several challenges such as better end-points, safety issues and trial design need to be addressed for further vaccine development to proceed.

Open Access Article

Schistosomiasis vaccines

Afzal A. Siddiqui, Bilal A. Siddiqui and Lisa Ganley-Leal
Pages 1192 - 1197
http://dx.doi.org/10.4161/hv.7.11.17017
Abstract | PDF

Schistosomiasis is a major neglected tropical disease of public health importance to a billion people. An estimated 200 million people are currently infected; an additional 779 million individuals are at risk to acquire the infection in 74 countries. Despite many years of implementation of mass anti-parasitic drug therapy programs and other control measures, this disease has not been contained and continues to spread to new geographic areas.  The discovery of a protective vaccine still remains the most potentially effective means for the control of this disease, especially if the vaccine provides long-term immunity against the infection. A vaccine would contribute to the reduction of schistosomiasis morbidity through induced immune responses leading to decrease in parasite load and reduced egg production. This vaccine could be administered to children between the ages of 3 and 12 years to prevent severe infection in a particularly high risk population. This review summarizes the current status of schistosomiasis vaccine development.

Open Access Article

Buruli ulcer

Thorbjorg Einarsdottir and Kris Huygen
Pages 1198 - 1203
http://dx.doi.org/10.4161/hv.7.11.17751
Abstract | Full Text | PDF

Buruli Ulcer (BU) is a neglected, necrotizing skin disease, caused by M. ulcerans, that can leave patients with prominent scars and lifelong disability. M. ulcerans produces a diffusible lipid toxin, mycolactone, essential for bacterial virulence. Prevention is difficult as little is known about disease transmission and there is no vaccine. There have been several recent advances in the field. These include sequencing of the bacterial genome and of the giant plasmid responsible for mycolactone synthesis, better understanding of the bacterial lifecycle and of the mechanism of action of the toxin. This work has revealed a number of possible vaccine candidates, some of which are shared with other mycobacteria, e.g. M. tuberculosis, while other targets are unique to M. ulcerans. In this review, we discuss several M. ulcerans vaccine targets and vaccination methods, and outline some of the gaps in our understanding of the bacterium and the immune response against it.

www.wiv-isp.be/Programs/communicable-infectious-diseases/Pages/EN-Immunology.aspx

Open Access Article

Leishmaniasis

Lukasz Kedzierski
Pages 1204 - 1214
http://dx.doi.org/10.4161/hv.7.11.17752
Abstract | PDF

Leishmaniasis is a disease that ranges in severity from skin lesions to serious disfigurement and fatal systemic infection. WHO has classified the disease as emerging and uncontrolled and estimates that the infection results in two million new cases a year. There are 12 million people currently infected worldwide, and leishmaniasis threatens 350 million people in 88 countries. Vaccination remains the best hope for control of all forms of the disease, and the development of a safe, effective and affordable antileishmanial vaccine is a critical global public-health priority. However, to date, no such vaccine is available despite substantial efforts by many laboratories. Main obstacle in vaccine design is the transition from the laboratory to the field and extrapolation of data from animal models to humans. This review discusses recent findings in the antileishmania vaccine field and current difficulties hampering vaccine implementation.

Open Access Article

Recombinant vaccines against Leptospirosis

Odir A. Dellagostin, André A. Grassmann, Daiane D. Hartwig, Samuel R. Félix, Éverton F. da Silva and Alan J. A. McBride
Pages 1215 - 1224
http://dx.doi.org/10.4161/hv.7.11.17944
Abstract | PDF

Leptospirosis is an important neglected infectious disease that occurs in urban environments, as well as in rural regions worldwide. Rodents, the principal reservoir hosts of pathogenic Leptospira spp., and other infected animals shed the bacteria in their urine. During occupational or even recreational activities, humans that come into direct contact with infected animals or with a contaminated environment, particularly water, are at risk of infection. Prevention of urban leptospirosis is largely dependent on sanitation measures that are often difficult to implement, especially in developing countries. Vaccination with inactivated whole-cell preparations (bacterins) has limited efficacy due to the wide antigenic variation of the pathogen. Intensive efforts towards developing improved recombinant vaccines are ongoing. During the last decade, many reports on the evaluation of recombinant vaccines have been published. Partial success has been obtained with some surface-exposed protein antigens. The combination of protective antigens and new adjuvants or delivery systems may result in the much-needed effective vaccine.

Open Access Article

Vaccination against trypanosomiasis: Can it be done or is the trypanosome truly the ultimate immune destroyer and escape artist?

Florencia La Greca and Stefan Magez
Pages 1225 - 1233
http://dx.doi.org/10.4161/hv.7.11.18203
Abstract | PDF

To date, human African trypanosomiasis (HAT) still threatens millions of people throughout sub-Sahara Africa, and new approaches to disease prevention and treatment remain a priority. It is commonly accepted that HAT is fatal unless treatment is provided. However, despite the well-described general symptoms of disease progression during distinct stages of the infection, leading to encephalitic complications, coma and death, a substantial body of evidence has been reported suggesting that natural acquired immunity could occur. Hence, if under favorable conditions natural infections can lead to correct immune activation and immune protection against HAT, the development of an effective anti-HAT vaccine should remain a central goal in the fight against this disease.
In this review, we will (1) discuss the vaccine candidates that have been proposed over the past years, (2) highlight the main obstacles that an efficient anti-trypanosomiasis vaccine needs to overcome and (3) critically reflect on the validity of the widely used murine model for HAT.

Open Access Article

A history of hookworm vaccine development

Brent Schneider, Amar R. Jariwala, Maria Victoria Periago, Maria Flávia Gazzinelli, Swaroop N. Bose, Peter J. Hotez, David J. Diemert and Jeffrey M. Bethony
Pages 1234 - 1244
http://dx.doi.org/10.4161/hv.7.11.18443
Abstract | PDF

The human hookworms Necator americanus and Ancylostoma duodenale remain among the most common infections of humans in areas of rural poverty in the developing regions of the world, with an estimated 1 billion people infected with one or more of these parasites. Herein, we review the nearly 100 years of research, development, animal testing, and fieldwork that have led to our current progress in recombinant hookworm vaccines. We begin with the identification of hookworm at the start of the 20th century in Southern US, then discuss the progress in developed countries to eliminate human hookworm infection, and then the industrial development and field use in the 1970s a canine hookworm vaccine(Ancylostoma caninum), and finally our progress to date in the development and clinical testing of an array of recombinant antigens to prevent human hookworm disease from N. americanus infection. Special attention is given to the challenges faced in the development of a vaccine against a blood-feeding nematode, including the epidemiology of infection (high prevalence of infection), pathogenesis (chronic infection that increases with the age of the host), and a robust immune response that fails to confer the protection in the host and a concomitant absence of correlates of protection by a successful vaccine could be developed and tested. Finally, we provide the optimal and acceptable profiles of a human hookworm vaccine, including the proposed indication, target population, and route of administration, as developed by the Human Hookworm Vaccine Initiative, the only group currently working on vaccines targeting this parasite.