Table of Contents

Volume 7, Issue 8

  August 2011

  Pages 801 - 890

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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 801
http://dx.doi.org/10.4161/hv.7.8.17596
PDF




NEWS, POLICY AND PROFILES

Open Access Article

News

Eva M. Riedmann
Pages 802 - 805
http://dx.doi.org/10.4161/hv.7.8.17597
Abstract | PDF

Successful Phase I study for novel Staphylococcus aureus vaccine
Influenza vaccination during pregnancy protects babies
Sinovac advances vaccine against human enterovirus 71
HIV weakness revealed
BiondVax’s universal flu vaccine successful in Phase II
Vaccine against renal cell carcinoma enters Phase III
Promising antigen for new TB vaccine: EspC
Vaxart’s first oral vaccine starts clinical trials

Open Access Article

Questions for Biotechs: Oxford-Emergent Tuberculosis Consortium

Adam Stoten
Pages 806 - 807
http://dx.doi.org/10.4161/hv.7.8.17598
PDF




PORTRAIT OF A LEADING VACCINOLOGIST

Open Access Article

A life passion for vaccines

Mariagrazia Pizza
Pages 808 - 810
http://dx.doi.org/10.4161/hv.7.8.17637
PDF




REVIEWS

Open Access Article

Transcutaneous and intradermal vaccination

Behazine Combadiere and Christelle Liard
Pages 811 - 827
http://dx.doi.org/10.4161/hv.7.8.16274
Abstract | PDF

Most vaccines are administered by intramuscular (IM) or subcutaneous (SC) routes, however, intradermal (ID) and transcutaneous (TC) techniques are regaining popularity. We will discuss in this review several factors that strongly justify the use of the cutaneous tissues and development of alternative methods for vaccination. That includes (1) our improved knowledge of skin physiology and better understanding of the barrier role of the horny layer, (2) the rationalization for targeting the different cutaneous layers, i.e. the epidermis, dermis, or hypodermis, (3) our advances in knowledge of the skin immune system, especially the plasticity of antigen-presenting cells (APCs) (i.e Langerhans cells (LC), dermal dendritic cells (DDC) and dermal macrophages) in the induction of immune responses, (4) the reduction of antigenic dose for some modes of cutaneous administration, (5) the increased need in needlefree vaccination strategies for developing countries to cope with blood contamination issues. Progress in skin immunization methods and better understanding of skin immunity allow proposing innovative and efficient vaccination strategies against infectious diseases.

Open Access Article

Meningococcal disease: The advances and challenges of meningococcal disease prevention

Ram Yogev and Tina Tan
Pages 828 - 837
http://dx.doi.org/10.4161/hv.7.8.16270
Abstract | PDF

Vaccination as a means to prevent meningococcal disease caused by Neisseria meningitidis is critical given the abrupt onset and rapid progression of this disease. Five serogroups-A, B, C, W-135, and Y-are responsible for the majority of cases. In developed countries, infants have the greatest risk of disease, with a smaller secondary peak observed in late adolescence. Vaccines utilizing the polysaccharide capsule are poorly immunogenic in young children but can reduce the incidence of meningococcal carriage in high risk groups. In contrast, protein conjugate vaccines to polysaccharide capsules A, C, W-135, and Y have broadened the population protection from disease but their effect on meningococcal carriage and transmission is yet unknown except for monovalent meningococcal C conjugate that has been shown to reduce carriage. Challenges remain in providing direct protection to infants and protection against meningococcal B disease. To date, outer membrane vesicle vaccines have been used to control meningococcal B disease in epidemic settings and vaccine candidates against subcapsular antigens are in development, but a vaccine that confers long-lasting protection is unavailable.




RESEARCH PAPERS

Open Access Article

A recombinant mutant abrin A chain expressed in Escherichia coli can be used as an effective vaccine candidate

Yan-Hui Han, Shan Gao, Wen-Wen Xin, Lin Kang and Jing-Lin Wang
Pages 838 - 844
http://dx.doi.org/10.4161/hv.7.8.16258
Abstract | PDF

We used site-directed mutagenesis to mutate two key amino acid residues, Glu164 and Arg167, of abrin A chain (ABRA), creating a mutant ABRA^E164AR167L. The mutant ABRA (mABRA) encoded by mABRA^E164AR167L was expressed in the cytoplasm of Escherichia coli, and used to develop an effective vaccine to protect mice against native abrin intoxication. The cytotoxicity of mABRA was dramatically reduced as compared to that of recombinant ABRA (rABRA) and native abrin, but the antigenicity and immunogenicity remained the same. Balb/c mice were vaccinated with purified mABRA, and survival was evaluated after challenge with native abrin. Mice that were given three vaccinations developed a protective immune response that was 100% protective against an intraperitoneal (i.p.) administration of 10×LD₅₀ of native abrin. Furthermore, the sera from immunized mice provided complete passive protection for naive mice. This study describes the generation of a substantial amount of mABRA from E. coli and the potential application of mABRA as an effective vaccine candidate for humans, to protect against a high-dose of native abrin.

Open Access Article

An evidence based protocol for the prevention of upper arm injury related to vaccine administration (UAIRVA)

Ian F. Cook
Pages 845 - 848
http://dx.doi.org/10.4161/hv.7.8.16271
Abstract | PDF

Upper arm injury related to vaccine administration (UAIRVA) is an infrequent but increasingly recognised complication of deltoid muscle vaccination.
Vaccine administration reported injury to the subdeltoid/subacromial bursa, anterior branch of the axillary nerve and the radial nerve presumably reflects the lack of awareness of the anatomical position of these structures in and near this muscle and the multiplicity of methods for the selection of the injection site in the muscle.
An evidence based protocol for safe vaccine administration into the deltoid muscle is presented. This was developed using anthropometric measurements of the surface anatomical landmarks in adults who regularly receive intramuscular injection of vaccines into the deltoid muscle (adults ≥ 65 years old) and mapping the position of structures potentially injured by injection observed in ultrasonographic and cadaveric studies.
The mid point of the muscle (midway between the acromion and the deltoid tuberosity) with the arm abducted to 60° is a safe site for injection. The protocol for vaccine administration in this way involves the vaccinee placing the hand on the ipsilateral hip with the vaccinator then placing their index finger on the acromion and their thumb on the deltoid tuberosity and administering the vaccine at midpoint between these anatomical landmarks.

Open Access Article

A highly specific antibody response after protein prime-peptide boost immunization with Eppin/B-cell epitope in mice

Zhengqiong Chen, Wei He, Yuzhang Wu, Ping Yan, Haiyang He, Ji Zhang, Xia Yang, Zigang Shen, Zhiqing Liang and Jintao Li
Pages 849 - 855
http://dx.doi.org/10.4161/hv.7.8.16279
Abstract | PDF

Eppin seems to be a promising target for developing immunocontraceptives for males. In an attempt to develop a safer vaccine, the immune response should be specifically directed according to its fertility inhibition mechanism. The mechanism of Eppin as an immunocontraceptive agent is now assumed to be the inhibitory effect of Eppin-specific antibody on sperm motility. Hence, to make Eppin a successful immunocontraceptive, avid and specific antibody responses have to be elicited. We had employed the inoculation modality of protein prime-peptide boost with rhEppin and epitope-based peptide, which has previously showed a satisfying result of fertility inhibition with minimal adverse effects. We here further explored the immunological features and efficiency of a protein prime-peptide boost strategy. The results of the present study showed that all the animals injected with rhEppin followed by epitope-based peptide boost, elicited enhanced specific anti-Eppin antibodies. The IgG subclasses of the antibodies generated by this regimen were primarily of IgG2b and IgG1 isotypes, and more importantly, the IgA level of epidydimis lavage was much higher, which correlated well with the results of cytokine profiles in spleen cell cultures. Furthermore, the results of peptide competition assays demonstrated that rhEppin alone prime-boost vaccination lead to a broader B-cell response while protein prime-epitope-peptide boosts directed the immune response mainly against the epitope. The results indicate that this immunization strategy may be advantageous in eliciting a highly specific humoral immune response.

Open Access Article

Hospitalization in Spain associated with malignant neoplasias of the vulva and vagina (1997-2008)

Ruth Gil-Prieto , Javier Cortés, José Manuel Ramón y Cajal, Pablo Viguera Ester and Angel Gil de Miguel
Pages 856 - 863
http://dx.doi.org/10.4161/hv.7.8.16280
Abstract | PDF

An important percentage of vulvar and vaginal cancers may be attributed to infections by the human papillomavirus. Although the incidence of invasive vulvar and vaginal cancers is low, it has remained stable over the past years. Hospital discharges related to malignant neoplasias and in situ carcinomas of the vulva and vagina from 1997 to 2008 were selected from the Minimum Data Set of the Ministry of Health in Spain. 17,883 hospital admissions related to vulvar and vaginal malignant neoplasias and 2,185 admissions related to in situ carcinomas of the vulva and vagina were gathered, with a hospitalization rate of 7,054 and 0.862 discharges per 100,000 women/year, respectively. The mean age of patients was 57 (SD:18) years, and the mean length of hospital stay was 8 (SD:10) days. There was a statistically significant increase in the hospitalization rate for malignant neoplasias and in situ carcinomas with increasing patient age. This increase was significant for all locations. Overall, there was a case fatality rate of 9.34% for vulvar and vaginal malignant neoplasias and 0.46% for in situ carcinomas of an external genital organ. Mortality and case fatality rates increased significantly throughout the length of the study. 92% of all deaths occurred in those older than 55 years of age. Mortality and case fatality rates also increased significantly with age. The hospitalization rate follows a north-south pattern. These data of the pre-anti-HPV vaccine era may be useful to develop cost-effectiveness models and strategies and evaluate the impact of HPV vaccination in Spain.

Open Access Article

Factors associated with increased vaccination in 2009 H1N1 school-located influenza vaccination programs

Christopher S. Ambrose and Frangiscos Sifakis
Pages 864 - 867
http://dx.doi.org/10.4161/hv.7.8.16281
Abstract | PDF

In the United States, school-located influenza vaccination (SLIV) programs have increased significantly in recent years. In June 2010, the Office of Inspector General issued a report regarding 38 elementary school H1N1 SLIV programs conducted in 6 localities in November/December 2009. By locality, there was a mean of 14 to 46 first doses of vaccine administered per 100 students. The locality that conducted programs in early November had a higher uptake rate than localities with later programs (46 vs 21 per 100 students; P<.01). Among localities with programs in mid- to late-November, the locality with programs after school hours had a lower uptake rate than the two localities with programs during school hours (16 vs 28, P=.05, and 16 vs 30, P<.01, respectively). These data suggest that future SLIV programs may achieve higher uptake rates if conducted during school hours with advance parental consent and when parental demand is highest.

Open Access Article

Efficacy and safety of the H1N1 monovalent vaccine in renal-transplant recipients and dialysis patients

Séverine Beaudreuil, Anne Krivine, Hadia Hebibi, Béatrice Ducot, Anne-Aurélie Mazet, Yassine Taoufik, Alexandre Seidowsky, Antoine Jacquet, Hans Kristian Lorenzo, Bernard Charpentier, Hélène Francois and Antoine Durrbach
Pages 868 - 873
http://dx.doi.org/10.4161/hv.7.8.16083
Abstract | PDF

Background: The (H1N)1v influenza virus infection emerged in 2009 as a serious disease in targeted populations. Herein, we report on the tolerability and efficacy of (anti-H1N1)v vaccination in dialysis and transplant patients.
Methods: 18 renal-transplant recipients (RTR) and 19 dialysis patients (DP) [12 patients treated with peritoneal dialysis (PDP), 7 patients treated with haemodialysis (HDP)] were enrolled. DPs received one monovalent H1N1 adjuvanted-vaccine injection, and RTRs received two unadjuvanted vaccine injections within a 21-day period. Serologic response was defined as a haemagglutination inhibition titre of >40 (seroprotection) and/or at least a four-fold increase in antibody titre from baseline (seroconversion).
Results: Seroprotection rate after vaccination was greater in DPs than RTRs (p = 0.007), as was seroconversion (p = 0.001). Serologic response was similar in PDPs and HDPs.
Conclusions:. Serologic response was satisfactory in DPs, whichever dialysis mode (DPD or HDP). It was low in RTRs as compared to DPs. Abstract word count 149




COMMENTARIES

Open Access Article

Should the chickenpox vaccine be included in the national immunization schedule in India?

Ramesh Verma, Mohan Bairwa, Suraj Chawla, Shankar Prinja and Meena Rajput
Pages 874 - 877
http://dx.doi.org/10.4161/hv.7.8.15685
Abstract | PDF

Varicella (chickenpox) is an acute, highly contagious viral disease with worldwide distribution. The highest prevalence occurs in the 4-10 year age group but tends to be more severe in adults. It may be fatal in neonates, immunocompromised persons, and normal adults, especially smokers. Varicella is usually a benign childhood disease, and rarely rated as an important public health problem, but this can be severe and even fatal in otherwise healthy children (<1 out of every 10,000 cases). Chickenpox can cause pneumonia (23 out of every 10,000 cases), and is an important risk factor for developing severe invasive “strep” (group A streptococcal disease). Complications of varicella include bacterial infections (up to 5% of cases), decreased platelets, arthritis, hepatitis, pneumonia (more commonly in adults) or encephalitis (1 in 10,000 cases), which may cause a failure of muscular coordination, sometimes resulting in persistent sequelae or death. Varicella is the leading cause of vaccine-preventable death in children. Universal vaccination can cause a dramatic reduction in the incidence of varicella, associated complications, hospitalizations and fatality rates. In India, due to the high cost of the vaccine, it would be difficult to vaccinate a large percentage of the children. The government of India should consider the inclusion of varicella vaccine in the National Immunization Schedule with the help of International agencies.

Open Access Article

Use of basophil activation test in the investigation of adverse effects to vaccines

Salvatore Chirumbolo
Pages 878 - 880
http://dx.doi.org/10.4161/hv.7.8.16272
Abstract | PDF

Diagnosis of adverse effects caused by vaccines mainly includes investigative approaches based on skin tests, histamine, tryptase and serum IgE levels which should allow to diagnose an IgE-mediated allergy reaction, most caused by additive components. Incidence of vaccine-related allergy and anaphylaxis due to vaccination are very poorly represented among population, based on the latest epidemiological and safety reports. Notwithstanding, routinely allergy diagnostic tools show many pitfalls and contradictory results when used to highlight an allergy onset or a clinical manifestation recalling an hypersensitivity reaction. Furthermore, adjuvants in vaccines may trigger innate cells response by toll-like receptors, thus eliciting a possible non-IgE mediated allergy phenomenon or causing B-cell activation and autoimmunity. A cellular test, such as a basophil activation test, or more widely a flow cytometry analysis of immune cells, might add new insights to the comprehension of allergy due to vaccination , thus ameliorating the diagnostic endowment in the hand of physicians.

Open Access Article

Indirect effects by meningococcal vaccines: Herd protection versus herd immunity

Michael Bröker
Pages 881 - 882
http://dx.doi.org/10.4161/hv.7.8.16273
Abstract | PDF

The term “herd immunity” for the indirect effect of meningococcal conjugate vaccines is inaccurate. A more appropriate term is “herd protection.”

Open Access Article

New generation typhoid vaccines: An effective preventive strategy to control typhoid fever in developing countries

Ramesh Verma, Mohan Bairwa, Suraj Chawla, Shankar Prinja and Meena Rajput
Pages 883 - 885
http://dx.doi.org/10.4161/hv.7.8.16282
Abstract | PDF

Typhoid fever is a serious systemic infection, caused by the enteric pathogen Salmonella enterica serovar Typhi, a highly virulent and invasive enteric bacterium. This disease occurs in all parts of world where water supplies and sanitation are substandard. These pathogens then travel to food, drinks and water through house-flies and other vectors. Globally, an estimated 12-33 million cases of enteric fever occur with 216,00 -600,000 deaths per year, almost exclusively in the developing countries. Health surveys conducted by the Health Ministry of India in the community development areas indicated a morbidity rate varying from 102-2219/100,000 population in different parts of the country. A limited study in an urban slum showed 1% of children up to 17 years of age suffer from typhoid fever annually. The continued high burden of typhoid fever and the alarming spread of antibiotic resistant strains led the World Health Organization (WHO), almost ten years ago, to recommend immunization using the two new-generation vaccines in school- aged children in areas where typhoid fever posed a significant problem and where antibiotic resistant strains were prevalent. Morbidity and mortality due to high incidence of typhoid fever favors the introduction of typhoid vaccine in routine immunization in India. This vaccine should be given at the age of 2 years with Vi antigen vaccine and at least one more dose be given at 5 years of age.

Open Access Article

Next-generation outer membrane vesicle vaccines against Neisseria meningitidis based on nontoxic LPS mutants

Peter van der Ley and Germie van den Dobbelsteen
Pages 886 - 890
http://dx.doi.org/10.4161/hv.7.8.16086
Abstract | PDF

Outer membrane vesicles (OMVs) have been used extensively as experimental vaccines against Neisseria meningitidis. Classical meningococcal OMV vaccines contain wildtype lipopolysaccharide (LPS) with a hexa-acylated lipid A moiety, which is a very potent activator of the TLR4 receptor. While this may make the LPS an effective "internal" adjuvant, it also contributes to vaccine reactogenicity. Reduction of endotoxic activity has therefore been essential for the application of meningococcal OMV vaccines in humans. Classical OMV vaccines have a reduced LPS content as a result of detergent extraction, mostly with deoxycholate. An alternative method is the use of meningococcal strains with genetically detoxified LPS, in particular where mutation in the lpxL1 gene has resulted in penta-acylated lipid A with strongly attenuated endotoxic activity. This allows the use of native OMVs without any need for LPS removal by detergent extraction, making it a much easier to produce and more versatile vaccine platform. Several groups have now started the development of native OMV vaccines based on non-toxic LPS mutants, and this Commentary provides an overview of the various approaches and results thusfar.