Table of Contents

Volume 7, Issue 10

  October 2011

  Pages 993 - 1111

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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 993
http://dx.doi.org/10.4161/hv.7.10.18259
PDF

Open Access Article

Human Vaccines & Immunotherapeutics

Ronald W. Ellis
Page 994
http://dx.doi.org/10.4161/hv.7.10.18260
Abstract | PDF

We are very pleased to broaden the scope and accordingly the name of our journal to Human Vaccines & Immunotherapeutics as of January. This broadening is a natural outgrowth of the evolution of technologies and approaches in our field, and acknowledges the increasing confluence and synergies between the fields of vaccines and immunotherapeutics.




NEWS, POLICY AND PROFILES

Open Access Article

News

Eva M. Riedmann
Pages 995 - 998
http://dx.doi.org/10.4161/hv.7.10.18273
Abstract | PDF

IOM report: Vaccines cause very few side effects
New TB vaccine to be tested in HIV infected people
Infant rotavirus vaccine may protect unvaccinated individuals
New potent and broadly effective HIV antibodies isolated
Early childhood immunization rates increasing in the US
Potential for TB vaccine in fighting cancer
Tweens and teens often missing vaccines
New study: How FluMist elicits protection




REVIEW

Open Access Article

Recent developments for Pseudomonas vaccines

Anurag Sharma, Anja Krause and Stefan Worgall
Pages 999 - 1011
http://dx.doi.org/10.4161/hv.7.10.16369
Abstract | PDF

Infections with Pseudomonas aeruginosa are a major health problem for immune-compromised patients and individuals with cystic fibrosis. A vaccine against
P. aeruginosa has long been sought after, but is so far not available. Several vaccine candidates have been assessed in experimental animals and humans, which include sub-cellular fractions, capsule components, purified and recombinant proteins. Unique characteristics of the host and the pathogen have complicated the vaccine development. This review summarizes the current state of vaccine development for this ubiquitous pathogen, in particular to provide mucosal immunity against infections of the respiratory tract in susceptible individuals with  cystic fibrosis.




PRODUCT HISTORY

Open Access Article

13-valent pneumococcal conjugate vaccine (PCV13)

Johanna MC Jefferies, Emily Macdonald, Saul N Faust and Stuart C Clarke
Pages 1012 - 1018
http://dx.doi.org/10.4161/hv.7.10.16794
Abstract | PDF

The thirteen valent pneumococcal conjugate vaccine (PCV13, Prevenar 13Ô) is the broader coverage successor to the highly effective seven valent vaccine (PCV7, PrevenarÔ) which has reduced rates of pneumococcal disease in many countries. Despite the success of PCV7, pneumococcal disease due to non-PCV7 serotypes remains a threat in many settings, in particular many developing countries with a high burden of pneumococcal disease where serotype 1 and 5 are among the most common serotypes. Disease due to certain non-PCV7 serotypes, in particular serotype 19A has also begun to increase in incidence in countries with widespread use of PCV7. PCV13 consists of thirteen pneumococcal capsular polysaccharides individually conjugated to the diphtheria-derived protein carrier CRM197. In addition to serotypes 4, 6B, 9V, 14, 18C, 19F and 23F included in PCV7, PCV13 also includes serotypes 1, 3, 5, 6A, 7F and 19A. PCV13 was licensed on the basis of non-inferiority trials and has proved to be at least as safe and effective as PCV7. PCV13 replaced PCV7 in the childhood immunisation schedules of the USA and UK in 2010 and is being rolled out to an increasing number of developing countries during 2011. Here we review the current literature regarding this vaccine, describing safety, efficacy, global serotype coverage and use and future directions.




MEETING REPORT

Open Access Article

Active immunotherapeutics forum–Advance phase III active immunotherapy programs Just how well did the pre-clinical and early clinical trials translate? Case Studies: With the benefit of hindsight, what are the three biggest lessons learned from pre-clinical and early clinical trials? Meeting report from Barcelona, May 12 2011

Will Colón
Pages 1019 - 1020
http://dx.doi.org/10.4161/hv.7.10.17335
Abstract | PDF

The approval of Provenge (Dendreon) in 2010 signaled the dawn of a new era in the development of active immunotherapeutics. For cancer treatment, the approval of Provenge® demonstrates that the immune system can effectively be harnessed to combat cancer. The outlook for active immunotherapies looks bright in terms of promising new approaches and candidates, as well as novel adjuvants and treatment regimens for therapy development.
Chairman:
Dr. David L. Urdal, Dendreon Corporation;
Speakers:
Dr. Carlos F. Santos, Accentia Biopharmaceuticals, Biovest International
Dr. Martin Falk, Merck KGaA
Dr. Valery R. Wagtmann, ALK
Dr. Jill O’Donnell-Tormey, Cancer Research Institute
Dr. Thomas Hinz, Paul-Ehrlich-Institute




SHORT REPORT

Open Access Article

Determinants of influenza vaccination among the adult and older Italian population with chronic obstructive pulmonary disease: A secondary analysis of the multipurpose ISTAT Survey on Health and Health Care use

Carlos Chiatti, Pamela Barbadoro, Anna Marigliano, Alessandra Ricciardi, Francesco Di Stanislao and Emilia Prospero
Pages 1021 - 1025
http://dx.doi.org/10.4161/hv.7.10.16849
Abstract | PDF

We analyzed seasonal flu vaccination rates among the Italian population suffering from Chronic Obstructive Pulmonary Disease (COPD) in order to identify socio-demographic and clinical determinants for vaccination.
We used data from the survey “Health and health care use in Italy”, which interviewed 5,935 persons (age 15 – 102 years) suffering from COPD in the period 2004-2005. For each respondent, information on socioeconomic and health conditions, smoking status and patterns of health care utilization were retrieved. After bivariate analysis, we used two multilevel regression models to assess determinants of vaccination among the adult and the older Italian population.
Overall 30.5% of adults (N=670) and 74.8% (N=2,796) of older people reported being vaccinated against seasonal flu. After controlling for potential confounders, older age increases the odds of vaccine uptake. Single marital status among the older people, smoking and not having contact with GPs in both age groups, are factors associated with non vaccination. Higher-educated elderly are less likely to be vaccinated, while coverage is higher among the wealthier adults.
Vaccine coverage among adults with COPD in Italy remains low, especially among those with no comorbidities, and aged less than 44 years. It is only in older age that vaccination rates increase substantially. We found several risk factors for non vaccination, such as smoking, single marital status, and not having contacts with GPs, which should be considered in developing strategies to increase the coverage of influenza vaccine among people with COPD in Italy.




RESEARCH PAPERS

Open Access Article

Comparison of four recombinant hepatitis B vaccines applied on an accelerated schedule in healthy adults

Francisco Hernández-Bernal, Arístides Aguilar-Betancourt, Virginia Aljovin, Gloria Arias, Carmen Valenzuela, Karen Pérez de Alejo, Karina Hernández, Orcilia Oquendo, Niurka Figueredo, Nelvis Figueroa, Alexis Musacchio, Gloria Véliz, Elizeth García, Alina D. Mollineda, Ana Isabel Juvier, Janette Trujillo, Aurora Delahanty, D. Ortega, Z. Cinza and Verena L. Muzio González
Pages 1026 - 1036
http://dx.doi.org/10.4161/hv.7.10.15989
Abstract | PDF

A post-marketing, double blind, randomised, controlled clinical trial to assess the immunogenicity and safety profiles of four commercially available recombinant hepatitis B vaccines was performed. The vaccines included in this study were Heberbiovac-HB^® (Heber Biotec S.A., Havana, Cuba), Euvax-B^®(LG Chemical Ltd., Seoul, Korea), Hepavax-Gene^®  (Greencross Vaccine Corp., Seoul, Korea), and Engerix-B^® (GlaxoSmithKline Biologicals, Rixensart, Belgium). Vaccines were administered intramuscularly to healthy adults in three 20mg doses at monthly intervals (0 - 1 -  2 months). Four hundred volunteers aged 18 to 45 years (average age, 35 years) non-reactive for serological markers of hepatitis B virus infection were vaccinated. Volunteers were randomly assigned (ratio 1:1:1:1) to one of the four treatment groups. The antibody response (anti-HBs) was assessed at days 60, 90 and 365 post-vaccination using a commercial kit. The four vaccines showed to be safe and highly immunogenic. Similar seroprotection rates (anti-HBs ≥10 IU/L) about one month after application of the second and third dose were obtained for Engerix-B^®, Hepavax-Gene^®, Euvax-B^®, and Heberbiovac-HB^® vaccines 96.7%, 96.6%, 100%, 100% and 98.8%, 89.5%, 100%, 100%, respectively.. Heberbiovac-HB^® vaccine achieved significantly higher geometric mean antibody titers (GMT) and rate of good and  hyper-responders at all time-points post-vaccination. The GMT on day 365 after full vaccination was significantly reduced in all groups compared to day 90, although Heberbiovac-HB^® showed the highest anti-HBs GMT and good-responders rate. The four vaccines were well tolerated and poorly reactogenic. No serious adverse events were observed. This study confirms an overall good immune response and rapid priming for the  four vaccines in the course of an accelerated schedule, with higher anti-HBs geometric mean concentrations and better responses for Heberbiovac-HB^®. [WHO primary Registry Number: RPCEC00000075].

Open Access Article

Cost-effectiveness analysis of pneumococcal polysaccharide vaccination from age 60 in São Paulo State, Brazil

Joao Tonolio Neto, Gabriela Tannus Branco de Araujo, Anna Gagliardi, Amanda Pinho, Laure Durand and Marcelo Fonseca
Pages 1037 - 1047
http://dx.doi.org/10.4161/hv.7.10.15987
Abstract | PDF

Vaccination of adults aged 60 years and older against Streptococcus pneumonia is not recommended in Brazil. The 23-valent polysaccharide pneumococcal vaccine (PPV23) is only available for institutionalized persons or with underlying diseases despite the substantial medical and economic burden related to pneumococcal infections in adults over than 59 years. The study aimed at evaluating the cost effectiveness of implementing a large PPV program in this population.
This analysis was performed using a static decision tree model. Demographic and epidemiological data were obtained from Brazilian official sources and international literature. Economic data were obtained from a study performed in 2007 in a public and a private hospital located in Sao Paulo. Vaccination was assumed to protect for 5 years with 60% effectiveness against bacteremic pneumococcal pneumonia (BPP) and 21% effectiveness against non bacteremic pneumococcal pneumonia (NBPP). Deterministic and sensitivity analyses were performed.
The pneumococcal polysaccharide vaccination saved 5,218 life year gained (LYG). The vaccination program was found to be cost effective in the social security and public health care perspectives with a mean incremental cost-effectiveness ratio of R$10,887 and R$8,281 per LYG respectively. Results were sensitive to the vaccine effectiveness against NBPP, the incidence and case-fatality rate of NBPP. From a societal perspective, PPV23 program for adults 60 and older was found to be cost-saving.
Pneumococcal polysaccharide vaccination is clinically and economically favored over the present vaccination strategy, in which persons aged over 59 years in Sao Paulo, have not been vaccinated.

Open Access Article

Two doses of pandemic influenza A(H1N1) vaccine: Tolerability in healthy young children in the Netherlands

Tessa M. van ’t Klooster, Jeanet M. Kemmeren, Hester E. de Melker, Patricia E. Vermeer-de Bondt and Nicoline A.T. van der Maas
Pages 1048 - 1054
http://dx.doi.org/10.4161/hv.7.10.16692
Abstract | PDF

During the 2009 influenza pandemic, children aged 6 months up to and including 4 years, without chronic illness, were vaccinated with two doses of Pandemrix® through mass vaccination in the Netherlands. During the vaccination campaign a warning was issued about fever after the second dose of Pandemrix®. Therefore, we investigated the tolerability of both doses Pandemrix® in these children. Among parents of children eligible for vaccination, 1500 questionnaires were distributed during both, the first and second mass vaccination session. We asked for the occurrence, time interval, and duration of local reactions and systemic adverse events (AEs). The responses were 36.7% and 29.5% after each dose, respectively. Local reactions were reported in 40.4% and 39.3%, most frequently, pain at the injection site. After the first and second dose, 29.6% and 30.7% of all children experienced fever (mean temperature 38.8{degree sign}C). Other systemic AEs were reported in 41.6% and 42.9% of the children. No differences were seen between the first and second dose for all reported AEs except for pallor. One child was hospitalized after the first dose, but a causal relation to the vaccination was considered improbable. In conclusion, fever was frequently reported in children 6 months up to and including 4 years of age after the first and second dose of Pandemrix®. However, for almost all AEs, including fever, no dose effect was observed. Reported AEs were mostly mild and all were transient.

Open Access Article

The effects of booster vaccination of hepatitis B Vaccine on anti-HBV surface antigen negative children 11-15 years after primary vaccination

Jun Yao, Jingjing Ren, Lingzhi Shen, Yongdi Chen, Xiaofeng Liang, Fuqiang Cui, Qian Li, Zhenggang Jiang and Fuzhen Wang
Pages 1055 - 1059
http://dx.doi.org/10.4161/hv.7.10.15990
Abstract | PDF

The twin aims of this study were to investigate the changes in anti-HBs IgG levels after booster vaccinations and to compare the effects of different vaccine doses in children aged 11-15 years who were both negative for HBsAg and had an Anti-HBs <10.0 mIU/mL after primary vaccination.
Children who were born between 1993 and 1998 and who had completed their Hepatitis B vaccination program in infancy were randomly recruited to the study. The participants were divided into three groups according to their anti-HBs IgG levels: group I had a level < 0.1 mIU/mL; group II 0.1 - <1.0 mIU/mL, and group III 1.0 - <10.0 mIU/mL.
The booster vaccination program comprised three (20μg) doses of HepB (CHO) vaccine administered at zero, one and six months after they are join this program: anti-HBs levels were measured one month after the first and third vaccinations.
Among 448 HBsAg-negative infants, anti-HBs seroconversion rates (defined as an anti-HBs >= 10 mIU/mL) after the first and third vaccinations were 85.5% and 98.6% respectively - these observed differences were statistically significant (χ2 [1dof] = 50.11, p<0.05). Seroconversion rates and GMTs after the first and third doses were significantly lower for group I children than the other two groups (p<0.05). Compared, the OR of being negative (anti-HBs<10mIU/ml) in group I after the first and the third dose were 7.66 (95%CI: 4.35-13.47, P<0.05) and 20.48 (95% CI: 2.36-177.67, P<0.05). So the anti-HBs titer levels decay to 10mIU/ml in 11-15 years of age children completed HepB Basic immunization, which need for booster immunization. The effect is better for those children with a relatively higher antibody titer before booster, and the effect of three doses booster is best.

Open Access Article

Immunogenicity and safety of ZOSTAVAX® approaching expiry potency in individuals aged ≥50 years

Robert Arnou, Anne Fiquet, Stéphane Thomas and Christine Sadorge
Pages 1060 - 1065
http://dx.doi.org/10.4161/hv.7.10.16480
Abstract | PDF

Background: Age is a major risk factor for herpes zoster (HZ) and its potential long-term complication post-herpetic neuralgia (PHN). Due to the significant burden of HZ and PHN on patients’ quality of life, it is vital that effective and well-tolerated vaccines are available to prevent HZ in older adults. ZOSTAVAX® vaccine was developed to prevent HZ and PHN in individuals ≥50 years (y) of age, and its clinical efficacy and safety have been demonstrated.
Aims and Methods: This phase 4, open-label, multicenter study was undertaken to assess the immunogenicity and safety of a single dose of ZOSTAVAX (refrigerator-stable formulation) given within 6 mo of its expiry date in individuals ≥50 y of age. The geometric mean fold rise (GMFR) from pre-vaccination to 4 weeks post-vaccination in varicella zoster virus (VZV) antibody titers was calculated. An acceptable antibody response was defined as a lower 95% confidence interval (CI) of GMFR >1.4. Solicited and unsolicited injection-site reactions and systemic adverse events were recorded.
Results: The GMFR in VZV antibody titers was 3.1 (95% CI: 2.6, 3.8), satisfying the criterion for an acceptable VZV antibody response to ZOSTAVAX (minimum requirement: 1.4 GMFR). An acceptable rise in VZV antibody titers was observed in individuals of 50–59 y of age (GMFR 3.9; 95% CI: 2.9, 5.1) and in those ≥60 y of age (GMFR 2.5; 95% CI: 1.9, 3.2). ZOSTAVAX was well tolerated; no serious adverse events were reported.
Conclusion: ZOSTAVAX elicits an acceptable immune response in immunocompetent individuals ≥50 y of age when stored as directed and administered during the 6 mo prior to expiration.

Open Access Article

Safety of a second dose of varicella vaccine administered at 4 to 6 years of age in healthy children in Argentina

Diego Fridman, Andrea Monti, Marie-Claude Bonnet, Judith Armoni and Daniel Stamboulian
Pages 1066 - 1071
http://dx.doi.org/10.4161/hv.7.10.17816
Abstract | PDF

Varicela Biken [Live varicella Biken vaccine (strain Oka)] is an effective and safe vaccine for the prevention of varicella infection.  Although the recommended schedule in all age groups (children, adolescents and adults) is a single dose, physicians in some countries follow the 2007 recommendation of the US Advisory Committee on Immunization Practices (ACIP) which recommends “implementation of a routine 2-dose varicella vaccination program for children, with the first dose administered at age 12--15 months and the second dose at age 4--6 years.”¹ Therefore, cases can arise when two doses of Varicela Biken are given even though the ACIP guidelines are a response to the US epidemiological situation and for US licensed products based on the Oka/Merck and the Oka-RIT strains (Varicela Biken is not registered in US).  The aim of this study is to ascertain the safety of a second dose of Varicela Biken in children who have been previously vaccinated with the same vaccine.
In this study, children, 4-6 years of age who had been previously vaccinated with Varicela Biken, received a single 0.5mL dose of live attenuated varicella virus vaccine containing at least 1000 Plaque Forming Units (PFU) attenuated live Varicella-zoster virus (Oka strain).  Participants were monitored for 30 minutes after vaccination.  Predefined injection site and systemic reactions were solicited during the subsequent seven days. Unsolicited injection site reactions and unsolicited systemic events were collected throughout the study. Any serious adverse events occurring throughout the study were reported to the sponsor’s pharmacovigilance department.
One hundred and twenty two children were recruited and all provided safety data.  There were no immediate adverse events or injection site reactions. Forty three percent of participants reported injection site reactions and 22.1% reported systemic reactions on solicitation during the seven days after vaccination. During the 30 day monitoring period, 43 participants reported a total of 66 adverse events.  Seven participants reported a total of eight unsolicited events that were assessed as related to the vaccine or where the relationship to vaccination was unknown.  Five of these eight events were injection site reactions and all were mild, systemic reactions included mild rash (1 case) and fever (2 cases). There was a single serious adverse event that was not related to the study medication (subject was a passenger in a motor vehicle accident). A second dose of Varicela Biken was well tolerated and showed no significant safety issues in this population of previously vaccinated children.

Open Access Article

Attitudes of seasonal influenza vaccination among healthcare worker and general community population after pandemic influenza A/H1N1 in Hangzhou

Shijun Liu, Hanyan Yuan, Yan Liu, Jian Du, Xiaoping Zhang, Jun Wang, Xinren Che and Erping Xu
Pages 1072 - 1076
http://dx.doi.org/10.4161/hv.7.10.16781
Abstract | PDF

Objective To know the attitude towards seasonal influenza vaccination among healthcare worker (HCWs) and general community population (GCPs) in the post-pandemic influenza A/H1N1 period. Method We conducted a cross-sectional investigation in the beginning of seasonal influenza vaccination between 2010 and 2011, employed logistic regression analysis to compute the relationship between the willingness of seasonal influenza vaccination and variables after pandemic influenza A/H1N1. Results A total of 489 participants including 126 HCWs and 363 GCPs completed the investigation. 33.33% individuals (34.92% HCWs vs 32.78% GCPs, p＞0.05) intended to accept the seasonal influenza vaccination after pandemic influenza A/H1N1. Individuals received seasonal influenza vaccination in the prior 3 years and monovalent A/H1N1 vaccination in 2009 were aggressive to vaccinate seasonal influenza vaccine with adjusted OR= 5.21(3.20~8.49) and 1.97(1.18~3.30).. According to the results of multivariable logistic regression model, the safety not efficacy of influenza vaccine was the significant factor for acceptability of seasonal influenza vaccination (OR: 3.11, 95%CI: 1.76~5.50). The positive attitude of serious degree of influenza A/H1N1 and occupational factor were also associated with the willingness of seasonal influenza vaccination and the adjusted ORs were 2.09(1.14~3.83) and 1.62(1.00~2.64). Conclusion Participants showed low acceptability of seasonal influenza vaccination after pandemic influenza A/H1N1. Need educational program concerning the advantages of vaccine, comprehensible information about possible adverse effects and the hazards of seasonal influenza disease, which might motivate individuals to accept seasonal influenza vaccination.

Open Access Article

Challenges and opportunities in the Israeli 2009 Pandemic Influenza Vaccination Program

Hagai Levine, Ran D Balicer, Daniel Laor and Itamar Grotto
Pages 1077 - 1082
http://dx.doi.org/10.4161/hv.7.10.17627
Abstract | PDF

Vaccines are a cornerstone in any pandemic influenza preparedness plan. Successful supplementary mass vaccination programs require proper advance planning. We aimed to identify general, and Israeli specific, challenges and opportunities before initiating the Israeli pandemic influenza vaccination program in order to better plan implementation of the program. Following the vaccination campaign the analysis was retrospectively examined in order to determine whether the challenges were properly identified and whether the opportunities were indeed realized. The major challenges identified were prioritization; ongoing communication with the public; balancing between central management and accessibility; and preventing vaccination errors. The major opportunity was expected to be the chance to enhance cooperation and communication between different organizations both within and outside of the health system at local, national and international levels. The vaccination program was planned based on this analysis. In retrospect, the analysis identified the key challenges and opportunities and appropriate measures were taken. However, the criticalness of acceptance of the vaccine among health care practitioners was not given sufficient attention and should be addressed in future vaccination programs. Analysis of global and local challenges and opportunities served as a useful tool for planning a pandemic influenza vaccination program. Lessons learned from this analysis could serve to foster cooperation and communication between various agencies in the event of planning rapid mass vaccination programs as well as for more routine public health vaccination campaigns.

Open Access Article

Enhanced immune response and protective efficacy of a Treponema pallidum Tp92 DNA vaccine vectored by chitosan nanoparticles and adjuvanted with IL-2

Feijun Zhao, Yimou Wu, Xiaohong Zhang, Jian Yu, Weiming Gu, Shuangquan Liu, Tiebing Zeng, Yuejun Zhang and Shiping Wang
Pages 1083 - 1089
http://dx.doi.org/10.4161/hv.7.10.16541
Abstract | PDF

Aims: In this study, the immune-modulatory and protective efficacy of using an interleukin-2 (IL-2) expression plasmid as a genetic adjuvant and chitosan (CS) nanoparticles as vectors to enhance a Tp92 DNA vaccine candidate- were investigated in a Treponema pallidum (Tp)rabbit challenge model.
Methods：Male New Zealand white rabbits were randomly assigned to groups (n = 18/group) and immunized intramuscularly with pTp92 based plasmid DNA constructs (100 μg of DNA/rabbit/immunization). Two weeks before Tp challenge (Week 8), three rabbits from each group were used to determine cytokine measurements and fifteen rabbits from each group were used for Tp challenge studies.
Results：CS vectoring of pTp92 or pIL-2 were both demonstrated to augment anti-Tp92 antibody levels induced by pTp92 DNA vaccines. Interestingly, the combination of CS vectored Tp92 and pIL-2 led to the greatest enhancements of anti-Tp92 antibodies and T cell proliferation (P < 0.05). At week 10 after the first immunization 8 post DNA vaccine immunization , 15 of the 18 rabbits in each group were challenged with Tp Nichols strain and monitored for skin lesions and ulcer lesgions. Ratioates of positive skin lesions and ratiotes of ulcer lesions in groups immunized with pTp92 were significantly lower than those of the empty vector or PBS groups (P < 0.05), demonstrating that pTp92 immunization elicited significant protective efficacy against the Tp Nichols strain challenge. CS vectored and pIL-2 adjuvanted pTp92 immunized animals exhibited the lowest rates of positive skin and ulcer lesions.
Conclusions: Intramuscular injection of pTp92 induced strong humoral and cellular immune responses and conferred protection from Tp challenge in rabbits. The use of CS as a pTp92 vector or pIL-2 as an adjuvant achieved a superior level of protective efficacy against Tp challenge, however CS vectored, IL-2 adjuvanted pTp92 immunization conferred the highest level of protective efficacy.

Open Access Article

Binding activity and immunogenic characterization of recombinant C-terminal quarter and half of the heavy chain of botulinum neurotoxin serotype A

Yun-Zhou Yu, Yao Ma, Yan-Xia Chen, Zheng-Wei Gong, Shuang Wang, Wei-Yuan Yu and Yun-Zhou Yu
Pages 1090 - 1095
http://dx.doi.org/10.4161/hv.7.10.16763
Abstract | PDF

In the present study, we explored and compared the binding activity and immunogenic characterization of the most effective part corresponding to C-terminal quarter of heavy chain of botulinum neurotoxin serotype A (AHc-C) with C-terminal half of heavy chain of botulinum neurotoxin serotype A (AHc). Firstly, the fully soluble AHc-C protein successfully expressed in Escherichia coli by co-expression with thioredoxin (Trx) was shown to bind with ganglioside as the AHc, indicating that the recombinant AHc-C protein retains a functionally active conformation. Furthermore, a solid-phase assay showed that the anti-AHc-C sera effectively inhibited the binding of AHc or AHc-C to the ganglioside GT1b, the first step in BoNT/A intoxication of neurons, as good as the anti-AHc sera. Finally, although the recombinant AHc-C protein still induced a high serum antibody titers and afforded protection level as the mice challenged with active botulinum neurotoxin serotype A, the immunization with AHc protein induced stronger protective potency than the AHc-C protein. The data presented in the report shows that there are the same ganglioside binding activity and different immunogenic characterization between the C-terminal quarter and half of heavy chain of botulinum neurotoxin serotype A. Therefore, the recombinant AHc-C protein can not only be developed into a minimal subunit candidate vaccine for prophylaxis against botulinum neurotoxin serotype A but also be used as a promising tool in the search for binding inhibitors and chimeric vaccines.




COMMENTARIES

Open Access Article

Perceptions of malaria and vaccines in Kenya

David Ojakaa, Emmanuel Yamo, Yvette Collymore, Antoinette Ba-Nguz and Allison Bingham
Pages 1096 - 1099
http://dx.doi.org/10.4161/hv.7.10.17496
Abstract | PDF

Malaria is a leading cause of morbidity and mortality in Kenya. To confront malaria, the Government of Kenya has been implementing and coordinating three approaches - vector control by distributing insecticide-treated bed nets and indoor residual spraying, case management, and the management of malaria during pregnancy. Immunization is recognized as one of the most cost-effective public health interventions. Efforts are underway to develop a malaria vaccine. The most advanced (RTS,S), is currently going through phase 3 trials. Although recent studies show the overwhelming support in the community for the introduction of a malaria vaccine, two issues - culture and the delivery of child immunization services - need to be considered.
Alongside the modern methods of malaria control described above, traditional methods coexist and act as barriers to attainment of universal immunization. The gender dimension of the immunization programme (where women are the main child caretakers) will also need to be addressed. There is an age dimension to child immunization programmes. Two age cohorts of parents, caregivers, or family members deserve particular attention. These are the youth who are about to initiate childbearing, and the elderly (particularly mother-in-laws who often play a role in child-rearing). Mothers who are less privileged and socially disadvantaged need particular attention when it comes to child immunization. Access to immunization services is often characterized in some Kenyan rural communities in terms of living near the main road, or in the remote inaccessible areas. Should a malaria vaccine become available in the future, a strategy to integrate it into the immunization programme in Kenya should take into account at least two issues. First, it must address the fact that alongside the formal approach in malaria control, there exist the informal traditional practices among communities. Secondly, it must address particular issues in the delivery of immunization services.

Open Access Article

The stem cell patent landscape as relevant to cancer vaccines

Shyh-Jen Wang
Pages 1100 - 1108
http://dx.doi.org/10.4161/hv.7.10.17022
Abstract | PDF

Cancer vaccine targeting cancer stem cells is proposed to serve as a potent immunotherapy. Thus, it would be useful to examine the main trends in stem cell patenting activity as a guide for those seeking to develop such cancer vaccines. We found that a substantial number of stem cell patents were granted up to the end of 2010, including ~2000 issued in the US. Many of these have been filed since 2001, including 7,551 applications in the US. Stem cell development, as evidenced by the numbers of PubMed articles, has matured steadily in recent years. However, the other metrics, such as the number of patent applications, the technology-science linkage and the number of patent assignees, have been stagnant. Moreover, the ownership of stem cell patents is still quiet fragmented across multiple organizations, and the number of stem cell patent assignees from the business sector has not increased significantly. Academic and nonprofit institutions not only account for a large share of stem cell patents but also apply for patents continually. Based on this analysis, the strength of stem cell resources seems to remain stagnant in recent years due to the ban on government funding of embryonic stem cell research. Furthermore, the patent prosecution or technical barriers in the field of stem cells would be another main reason that the number of US-issued stem cell patents for each application have been in gradual decline since 2000. Therefore, we consider stem cell technology to still be under development.

Open Access Article

Introduction of a second dose of measles in National immunization program in India: A major step towards eradication

Ramesh Verma, Pardeep Khanna, Mohan Bairwa, Suraj Chawla, Shankar Prinja and Meena Rajput
Pages 1109 - 1111
http://dx.doi.org/10.4161/hv.7.10.16890
Abstract | PDF

Measles is a highly infectious, acute respiratory illness that is caused by a virus of the genus Morbillivirus. The disease infects nearly 30 million children each year, and deaths usually occur from complications related to pneumonia, diarrhoea and malnutrition. A systematic review of published Indian literature depicts the median case fatality ratio (CFR) of measles to be 1.6%. Through immunization, measles deaths dropped a remarkable 78% from 733,000 in 2000 to 164,000 in 2008. As of 2008, 192 of 193 Member States of WHO use 2 doses of measles vaccine in their National immunization programs, India being the only exception. The Millennium Development Goal (MDG) 4 aims to reduce by two-thirds between 1990 and 2015 the under-five mortality rate (U5MR) in the world. Per the draft comprehensive Multi Year Strategic Plan (cMYP, 2010-17) for immunization of India, the country aims to reduce measles-related mortality by 90% by 2013 when compared to 2000. As recommended by the National Technical Advisory Group on Immunization (NTAGI), the implementation strategy of the second dose of measles vaccine at the state level is determined by the underlying performance of the routine immunization program. The second dose in the national immunization schedule gives extra immunity against measles infection that renders children more susceptible to secondary pneumonia and diarrhoeal diseases, which are the primary causes of under-5 child mortality in India.