Table of Contents

Volume 8, Issue 12

  December 2012

  Pages 1739 - 1911

Special Focus: Meningococcal Vaccines and Disease

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 Issue Catalogue (MARC XML)

EDITOR'S CORNER

Open Access Article

Letter from the Editor

Ronald Ellis and Eva M. Riedmann
Pages 1739 - 1740
http://dx.doi.org/10.4161/hv.23364
Full Text | PDF




NEWS, POLICY AND PROFILES

Open Access Article

Human Vaccines & Immunotherapeutics: News

Eva M. Riedmann
Pages 1741 - 1744
http://dx.doi.org/10.4161/hv.23373
Abstract | Full Text | PDF

Two therapeutic HPV vaccine candidates successful in phase 1

Flu shot may prevent heart attacks and stroke

CDX-1401 combined with TLR agonist: Positive phase 1 results

Three MRSA vaccines in early clincial trials

Ovarian cancer vaccine candidate DPX-Survivac: Positive interim results from phase 1

Chinese biotech partnership brings first hepatitis E vaccine to the market

Therapeutic vaccine for treatment of genital herpes enters phase 2

Visionary concept: Printable vaccines

Open Access Article

Profile: ImmunoCellular Therapeutics Ltd.

John S. Yu
Page 1745
http://dx.doi.org/10.4161/hv.23357
PDF





New targets

REVIEWS

Therapeutic vaccination to treat chronic infectious diseases: Current clinical developments using MVA-based vaccines

Houda Boukhebza, Nadine Bellon, Jean Marc Limacher and Geneviève Inchauspé
Pages 1746 - 1757
http://dx.doi.org/10.4161/hv.21689
Abstract | Full Text | PDF

A famous milestone in the vaccine field has been the first successful vaccination against smallpox, in 1798, by Edward Jenner. Using the vaccinia cowpox virus, Jenner was able to protect vaccinees from variola or smallpox. The Modified Virus Ankara (MVA) poxvirus strain has been one of the vaccines subsequently developed to prevent smallpox infection and was selected by the US government in their Biodefense strategy. Progress in molecular biology and immunology associated with MVA infection has led to the development of MVA as vaccine platform, both in the field of preventive and therapeutic vaccines. This later class of therapeutics has witnessed growing interest that has translated into an increasing number of vaccine candidates reaching the clinics. Among those, MVA-based therapeutic vaccines have addressed four major chronic infections including viral hepatitis, AIDS, human papillomavirus-linked pathologies and tuberculosis. Clinical trials encompass phase 1 and 2 and have started to show significant results and promises.

Universal fungal vaccines: Could there be light at the end of the tunnel?

Mawieh Hamad
Pages 1758 - 1763
http://dx.doi.org/10.4161/hv.21838
Abstract | Full Text | PDF

The complex nature of fungal pathogens, the intricate host-pathogen relationship and the health status of subjects in need of antifungal vaccination continue to hamper efforts to develop fungal vaccines for clinical use. That said, the rise of the universal vaccine concept is hoped to revive fungal vaccine research by expanding the pool of vaccine candidates worthy of clinical evaluation. It can do so through antigenic commonality-based screening for vaccine candidates from a wide range of pathogens and by reassessing the sizable collection of already available experimental and approved vaccines. Development of experimental vaccines protective against multiple fungal pathogens is evidence of the utility of this concept in fungal vaccine research. However, universal fungal vaccines are not without difficulties; for instance, development of vaccines with differential effectiveness is an issue that should be addressed. Additionally, rationalizing the development of universal fungal vaccines on health or economic basis could be contentious. Herein, universal fungal vaccines are discussed in terms of their potential usefulness and possible drawbacks.

SHORT REPORT

A dengue DNA vaccine formulated with Vaxfectin^® is well tolerated, and elicits strong neutralizing antibody responses to all four dengue serotypes in New Zealand white rabbits

Kanakatte Raviprakash, Thomas Luke, John Doukas, Janine Danko, Kevin Porter, Timothy Burgess and Tadeusz Kochel
Pages 1764 - 1768
http://dx.doi.org/10.4161/hv.21806
Abstract | Full Text | PDF

A tetravalent DNA vaccine formulated with Vaxfectin adjuvant was shown to elicit high levels of neutralizing antibody against all four dengue virus serotypes (Porter et al.,¹⁶), warranting further testing in humans. In preparation for a phase 1 clinical testing, the vaccine and the adjuvant were manufactured under current good manufacturing practice guidelines. The formulated vaccine and the adjuvant were tested for safety and/or immunogenicity in New Zealand white rabbits using a repeat dose toxicology study. The formulated vaccine and the adjuvant were found to be well tolerated by the animals. Animals injected with formulated vaccine produced strong neutralizing antibody response to all four dengue serotypes.

RESEARCH PAPER

Immunogenicity and immune modulatory effects of in silico predicted L. donovani candidate peptide vaccines

Mona E.E. Elfaki, Eltahir A.G. Khalil, Anne S. De Groot, Ahmed M. Musa, Andres Gutierrez, Brima M. Younis, Kawthar A.M. Salih and Ahmed M. El-Hassan
Pages 1769 - 1774
http://dx.doi.org/10.4161/hv.21881
Abstract | Full Text | PDF

Visceral leishmaniasis (VL) is a serious parasitic disease for which control measures are limited and drug resistance is increasing. First and second generation vaccine candidates have not been successful. The goal of the present study was to select possibly immunogenic L. donovani donovani GP63 peptides using immunoinformatics tools and to test their immunogenicity in vitro. The amino acid sequence of L. donovani donovani GP63 [GenBank accession: ACT31401] was screened using the EpiMatrix algorithm for putative T cell epitopes that would bind to the most common HLA class II alleles (DRB1*1101 and DRB1*0804) among at–risk populations. Four T cell epitopes were selected from nine potential candidates. Stimulation of whole blood from healthy volunteers using the peptides separately produced mean IFN-γ and IL-4 levels that were not significantly different from negative controls, while the pooled peptides produced a moderate IFN-γ increase in some volunteers. However, mean IL-10 levels were significantly reduced for all individuals compared with controls. The immunogenicity of these epitopes may be harnessed most effectively in a vaccine delivered in combination with immune-modulating adjuvants.

COMMENTARY

Open Access Article

Production of EV71 vaccine candidates

Pele Chong, Shih-Yang Hsieh, Chia-Chyi Liu, Ai-Hsiang Chou, Jui-Yuan Chang, Suh-Chin Wu, Shih-Jen Liu, Yen-Hung Chow, Ih-Jen Su and Michel Klein
Pages 1775 - 1783
http://dx.doi.org/10.4161/hv.21739
Abstract | PDF

Enterovirus 71 (EV71) is now recognized as an emerging neurotropic virus in Asia and with Coxsackie virus (CV) it is the other major causative agent of hand-foot-mouth diseases (HFMD). Effective medications and/or prophylactic vaccines against HFMD are urgently needed. From a scientific (the feasibility of bioprocess, immunological responses and potency in animal challenge model) and business development (cost of goods) points of view, we in this review address and discuss the pros and cons of different EV71 vaccine candidates that have been produced and evaluated in animal models. Epitope-based synthetic peptide vaccine candidates containing residues 211–225 of VP1 formulated with Freund’s adjuvant (CFA/IFA) elicited low EV71 virus neutralizing antibody responses, but were protective in the suckling mouse challenge model. Among recombinant EV71 subunits (rVP1, rVP2 and rVP3) expressed in E. coli, purified and formulated with CFA/IFA, only VP1 elicited mouse antibody responses with measurable EV71-specific virus neutralization titers. Immunization of mice with either a DNA plasmid containing VP1 gene or VP1 expressed in Salmonella typhimurium also generated neutralizing antibody responses and protected animals against a live EV71 challenge. Recombinant EV71 virus-like particles (rVLP) produced from baculovirus formulated either with CFA/IFA or alum elicited good virus neutralization titers in both mice and non-human primates, and were found to be protective in the suckling mouse EV71 challenge model. Synthetic peptides or recombinant EV71 subunit vaccines (rVP1 and rVLP) formulated in alum were found to be poorly immunogenic in rabbits. Only formalin-inactivated (FI) EV71 virions formulated in alum elicited cross-neutralizing antibodies against different EV71 genotypes in mice, rabbits and non-human primates but induced weak neutralizing responses against CAV16. From a regulatory, economic and market acceptability standpoint, FI-EV71 virion vaccines are the most promising candidates and are currently being evaluated in human clinical trials. We further describe and analyze some new bioprocesses technologies that have great potential applications in EV71 vaccine development. This review also demonstrates the opportunities and challenges that the Asian vaccine industry faces today.




HIV

REVIEW

Immune reconstitution and vaccination outcome in HIV-1 infected children: Present knowledge and future directions

Alberto Cagigi, Nicola Cotugno, Carlo Giaquinto, Luciana Nicolosi, Stefania Bernardi, Paolo Rossi, Iyadh Douagi and Paolo Palma
Pages 1784 - 1794
http://dx.doi.org/10.4161/hv.21827
Abstract | Full Text | PDF

Current evidence on routine immunization of HIV-1 infected children point out the need for a special vaccine schedule in this population. However, optimal strategies for identifying individuals susceptible to infections, and then offering them sustained protection through appropriate immunization schedule, both in terms of timing and number of vaccine doses, still remain to be elucidated.

Understanding the degree of immune recovery after HAART initiation is important in guiding administration of routine vaccination in HIV-1 infected children. Although quantitative measures (e.g., CD4+ T-cell counts and immunoglobulin levels) are frequently performed to evaluate immune parameters, these measures do not fully mirror functional immune recovery. Here, we will review the status of single mandatory and recommended vaccines for HIV-1 infected children in relation to immune recovery after HAART initiation with the aim of identifying new means to help design personalized vaccine schedules for this population.

COMMENTARY

HIV vaccines: Can CD4⁺ T cells be of help?

Eva Van Braeckel and Geert Leroux-Roels
Pages 1795 - 1798
http://dx.doi.org/10.4161/hv.21760
Abstract | Full Text | PDF

Defining immune correlates of protection against the human immunodeficiency virus (HIV) remains a major challenge. While the role of neutralizing antibodies and CD8⁺ T cell responses has been widely acknowledged and applied in vaccine development, little vaccine candidates have focused on CD4⁺ T cells. As the main target of HIV, CD4⁺ T cells play a pivotal role in HIV infection. An HIV vaccine that elicits strong, multi-specific, polyfunctional and persisting CD4⁺ T cell responses would therefore have the potential of lowering viral set point when HIV infection occurs or reducing viral load in already infected patients. In a combined approach with neutralizing antibodies and CD8⁺ T cells, CD4⁺ T cells cannot only enhance the magnitude, quality and durability of the desired antibody response, but will also provide the help needed to induce and maintain effective antiviral CD8⁺ T cell responses. In addition, the disease-modifying potential of the CD4⁺ T cell response, by lowering viral set point and/or viral load and thus probability of transmission, may be beneficial both at the individual and public health level.




Immunotherapy

CASE REPORT

CIMAvax EGF vaccine for stage IIIb/IV non-small cell lung carcinoma

Jian Y. Cheng and Ratnavelu Kananathan
Pages 1799 - 1801
http://dx.doi.org/10.4161/hv.21744
Abstract | Full Text | PDF

This case report documents the use of the CIMAvax Epidermal Growth Factor vaccine regimen in a 54 y old female with stage IIIb non-small cell lung carcinoma. Even after 48 mo since diagnosis her ECOG performance remains at zero. Further, this report documents a reaction to the vaccine of grade 3 severity not previously documented.

RESEARCH PAPERS

Prevention of infection in immunosuppressive patients with autoimmune nephrosis by using an immunostimulating bacterial lysate Broncho-vaxom

Miao Zhang, Hong Luan, Qian Zhang, Le Wang, Yong-Man Lv, Fan He, Yan Chen, Hong-Bing Zeng, Ying Yao and Qin Liu
Pages 1802 - 1807
http://dx.doi.org/10.4161/hv.21874
Abstract | Full Text | PDF

The utilization of immunosuppressive agents presents patients with autoimmune nephrosis at a high risk of infection. The present trial was to investigate the efficacy and safety of Broncho-Vaxom on preventing infection in immunosuppressive patients with autoimmune nephrosis.
Methods: 40 patients with autoimmune nephrosis were randomly divided into two groups. The control group (20 cases) routinely received corticosteroid and (or) immunosuppressive therapy, while the treatment group (20 cases) received a capsule containing 7 mg Broncho-Vaxom daily for the first 10 d of each month for 3 consecutive months on the basis of conventional corticosteroid and (or) immunosuppressive therapy. The condition of infection and blood lymphocyte were assessed.
Results: 4 patients in the treatment group and 5 patients in the control group were lost during the follow-up period. 25% of patients in the treatment group and 40% of patients in the control group suffered infection. There was no difference in the incidence of infection between the two groups (p > 0.05), while Broncho-Vaxom treated patients suffered a shorter infection period and of which fewer patients need to receive antibiotics therapy (p < 0.05). After the treatment with Broncho-Vaxom, the total number of blood T lymphocyte, proportion of CD4⁺ T lymphocyte, CD4⁺/CD8⁺ reduced less and the serum IgG rose more obviously (p < 0.05), but the blood lymphocyte, B lymphocyte, CD8⁺ T lymphocyte, IgA and IgM have no differences between the two groups (p > 0.05).
Conclusion: Broncho-Vaxom might be a good choice for preventing the respiratory infection in nephrosis, especially in the patients under the therapy of immunosuppressive agents.

Maturation of morphology, phenotype and functions of murine bone marrow-derived dendritic cells(DCs) induced by polysaccharide Kureha(PSK)

Yonggang Tan, Yiming Meng, Zuozhou Wang, Fengping Shan, Qiushi Wang and Ning Zhang
Pages 1808 - 1816
http://dx.doi.org/10.4161/hv.21993
Abstract | Full Text | PDF

The aim of this work was to evaluate the influence of protein-bound polysaccharide Kureha(PSK) on murine dendritic cells (DCs). These impacts of PSK on DCs from bone marrow derived DCs(BMDCs) were assessed with inverted phase contrast microscope, conventional scanning electron microscopy (SEM), transmission electron microscopy (TEM) for morphology, fluorescence activated cell sorting (FACS) analysis, cytochemistry assay for key surface molecules, FITC-dextran for phagocytosis, bio-assay and enzyme linked immunosorbent assay (ELISA) for cytokine production. We found that under the influence of PSK, immature DCs changed into mature DCs with decrease of antigens up-taking, simultaneously high expression of key surface molecules of the MHC classII,CD40, CD80, CD86 and CD83 as well as more production of IL-12p70 and tumor necrosis factor α (TNF-α). These data indicate that PSK could markedly promote maturation of DCs and this adjuvant-like activity may have potential therapeutic value in vaccine preparation.




Technologies

REVIEWS

Phage display—A powerful technique for immunotherapy: 1. Introduction and potential of therapeutic applications

Justyna Bazan, Ireneusz Całkosiński and Andrzej Gamian
Pages 1817 - 1828
http://dx.doi.org/10.4161/hv.21703
Abstract | Full Text | PDF

One of the most effective molecular diversity techniques is phage display. This technology is based on a direct linkage between phage phenotype and its encapsulated genotype, which leads to presentation of molecule libraries on the phage surface. Phage display is utilized in studying protein-ligand interactions, receptor binding sites and in improving or modifying the affinity of proteins for their binding partners. Generating monoclonal antibodies and improving their affinity, cloning antibodies from unstable hybridoma cells and identifying epitopes, mimotopes and functional or accessible sites from antigens are also important advantages of this technology. Techniques originating from phage display have been applied to transfusion medicine, neurological disorders, mapping vascular addresses and tissue homing of peptides. Phages have been applicable to immunization therapies, which may lead to development of new tools used for treating autoimmune and cancer diseases. This review describes the phage display technology and presents the recent advancements in therapeutic applications of phage display.

Phage display—A powerful technique for immunotherapy: 2. Vaccine delivery

Justyna Bazan, Ireneusz Całkosiński and Andrzej Gamian
Pages 1829 - 1835
http://dx.doi.org/10.4161/hv.21704
Abstract | Full Text | PDF

Phage display is a powerful technique in medical and health biotechnology. This technology has led to formation of antibody libraries and has provided techniques for fast and efficient search of these libraries.

The phage display technique has been used in studying the protein-protein or protein-ligand interactions, constructing of the antibody and antibody fragments and improving the affinity of proteins to receptors.

Recently phage display has been widely used to study immunization process, develop novel vaccines and investigate allergen-antibody interactions. This technology can provide new tools for protection against viral, fungal and bacterial infections. It may become a valuable tool in cancer therapies, abuse and allergies treatment. This review presents the recent advancements in diagnostic and therapeutic applications of phage display. In particular the applicability of this technology to study the immunization process, construction of new vaccines and development of safer and more efficient delivery strategies has been described.




Hepatitis

REVIEW

Review of 10 years of marketing experience with Chinese domestic inactivated hepatitis A vaccine Healive^®

Jun-Yu Wu, Yan Liu, Jiang-Ting Chen, Ming Xia and Xiao-Mei Zhang
Pages 1836 - 1844
http://dx.doi.org/10.4161/hv.21909
Abstract | Full Text | PDF

In 2002, the first Chinese domestic preservative-free inactivated hepatitis A vaccine, Healive^®, was introduced in China. It is highly immunogenic, and provides lasting protection in healthy individuals and generates protective levels of antibodies in other at-risk individuals. Over 10 years since its first licensure, postmarketing surveillance data have confirmed the outstanding safety profile of the vaccine. Comparative clinical trials indicated that Healive^® induce equal or similar immunogenicity with other currently available inactivated hepatitis A vaccines and are interchangeable for the course of HAV immunization in Chinese children. The vaccine is effective in curbing outbreaks of hepatitis A due to rapid seroconversion and the long incubation period of the disease. Additional issues surrounding the use of the vaccine are also reviewed.

RESEARCH PAPER

Revaccination of non- and low- responders after a standard three dose hepatitis B vaccine schedule

Ke Han, Xiaoping Shao, Huizhen Zheng, Chenggang Wu, Jianqiong Zhu, Xiaoli Zheng and Yonghui Zhang
Pages 1845 - 1849
http://dx.doi.org/10.4161/hv.21818
Abstract | Full Text | PDF

Background:

Guangdong province of China is HBV high endemicity and 1.6 million neonates are administrated 5 μg yeast recombinant anti-HBV vaccine each year. But few studies are performed to evaluate the immunogenicity and revaccination effect on non- and low- responders.

Methods:

2,199 children were administered intramuscularly with 5 μg vaccine at 0, 1 and 6 mo after birth. A 3 ml blood sample was drawn from each infant 1 mo after the third dose for determination of anti-HBs level. Three additional doses (10 μg each) were given to non- and low- responders.

Results:

Of 1,814 subjects, 3.1% were non-responders (anti-HBs titer < 10 mIUml⁻¹) and 28.9% were low-responders (anti-HBs ≥ 10 mIUml⁻¹ and < 100 mIUml⁻¹). Low birth weight (LBW) was a risk factor for non- and low- responders (RR = 1.6, 95%CI = 1.2–2.0). After revaccination, of the 34 non-responders, 14.7% became low-responders and 85.3% became responders. Of the 74 low-responders, 21.6% remained at the same level and 78.4% shifted into responder category.

Conclusions:

Based on the lower responding rate after the primary immunization cycle and the higher responding rate after the additional cycle, measurement of anti-HBs level should be considered for people who had been immunized with three-dose 5 μg HB vaccine in Guangdong, especially for specific populations including LBW infants, healthcare workers, and patients with immunodeficiency disorders. An amount of 10 μg vaccine should be revaccinated to any non- and low- responders to provide adequate seroprotection.




Influenza

RESEARCH PAPERS

Persistence of influenza vaccine-induced antibody in lung transplant patients and healthy individuals beyond the season

Jill J. Severson, Katelyn R. Richards, John J.M. Moran and Mary S. Hayney
Pages 1850 - 1853
http://dx.doi.org/10.4161/hv.21735
Abstract | Full Text | PDF

Background: The timing of influenza vaccination and susceptibility to re-circulating virus in the population is influenced by the persistence of seroprotection. Immunosuppressed transplant patients are known to have lower antibody response rates than healthy individuals, but acceptable antibody concentrations are achieved. The duration of this seroprotection beyond a single season has not been evaluated in either healthy or immunosuppressed populations.

Methods: Influenza antibody concentrations against viruses no longer included in the vaccine were measured in serum by hemagglutination inhibition assay annually following vaccination of 73 lung transplant participants and 27 healthy controls. Seroprotection was defined as a titer of ≥ 1:40 and was compared between groups over the measured term using Fisher’s exact tests.

Results: Seroprotection rates for influenza A and B strains at one year following immunization were 100% for lung transplant and healthy controls. Rates at two years for the influenza A strains were 65–74% for lung transplant vs. 77–100% in healthy controls. Rates for influenza B strains two years following immunization were 27–50% for lung transplant vs. 16–38% in healthy controls. (Fisher’s exact test; not significant for between group comparisons; p < 0.05 for between season comparisons)

Conclusions: Vaccine-induced antibody persistence appears to be influenced more by the vaccine virus strain than the immune status of the vaccinated individuals. Seroprotection rates are high 12 mo following influenza vaccination but wane over the second year, particularly for influenza B viruses. Annual influenza immunization is indicated, even for healthy individuals and even when the vaccine viruses do not change.

Immune response to 2009 H1N1 vaccine in HIV-infected adults in Northern Thailand

Nuntisa Chotirosniramit, Patcharaphan Sugandhavesa, Linda Aurpibul, Sunida Thetket, Natthapol Kosashunhanan, Taweewat Supindham, Panuwat Wongkulab, Quanhathai Kaewpoowat, Kanokporn Chaiklang, Oranitcha Kaewthip, Piyathida Sroysuwan, Antika Wongthanee, Hatairat Lerdsamran, Pilaipan Puthavathana and Khuanchai Suparatpinyo
Pages 1854 - 1859
http://dx.doi.org/10.4161/hv.21820
Abstract | Full Text | PDF

Background:

In late 2009, the Thai Ministry of Public Health provided two million doses of the monovalent pandemic influenza H1N1 2009 vaccine (Panenza^® Sanofi Pasteur), which was the only vaccine formulation available in Thailand, to persons at risk of more severe manifestations of the disease including HIV infection. Several studies have shown poorer immune responses to the 2009 H1N1 vaccines in HIV-infected individuals. There are limited data in this population in resource-limited countries.

Results:



At day 28 post-vaccination, seroconversion was found in 32.0% (95%CI 24.5 - 40.2) of the HIV-infected group and 35.0% (95%CI 15.4- 59.2) of the healthy controls (p = 0.79). Seroprotection rate was observed in 33.3% (95%CI 25.8–41.6) and 35.0% (95%CI 15.4–59.2) of the HIV-infected group and the control group, respectively (p = 0.88). Among HIV-infected participants, the strongest factor associated with vaccine response was age 42 y or younger (p = 0.05).

Methods:


We evaluated the immunogenicity of a single, 15µg/0.5ml dose of a monovalent, non-adjuvanted 2009 H1N1 vaccine in 150 HIV-infected Thai adults and 20 healthy controls. Immunogenicity was measured by hemagglutination inhibition assay (HI) at baseline and 28 d after vaccination. Seroconversion was defined as 1) pre-vaccination HI titer < 1:10 and post-vaccination HI titer ≥ 1:40, or 2) pre-vaccination HI titer ≥ 1:10 and a minimum of 4-fold rise in post-vaccination HI titer. Seroprotection was defined as a post-vaccination HI titer of ≥ 1:40.

Conclusions:


A low seroconversion rate to the 2009 H1N1 vaccine in both study groups, corresponding with data from trials in the region, may suggest that the vaccine used in our study is not very immunogenic. Further studies on different vaccines, dosing, adjuvants, or schedule strategies may be needed to achieve effective immunization in HIV-infected population.

Acceptance and rejection of influenza vaccination by pregnant women in southern Iran: Physicians' role and barriers

Behnam Honarvar, Neda Odoomi, Mojtaba Mahmoodi, Golnar Sami Kashkoli, Fatemeh Khavandegaran, Kamran Bagheri Lankarani and Mohsen Moghadami
Pages 1860 - 1866
http://dx.doi.org/10.4161/hv.22008
Abstract | Full Text | PDF

Objective: Vaccination provides the most effective protection against maternal, fetal and neonatal complications of influenza infection. This study aimed to determine the uptake rate of influenza vaccination including 2009 pandemic H1N1 influenza and seasonal influenza vaccination and the reasons for acceptance or rejection among pregnant women.

Result: Mean age of the 416 pregnant women enrolled in this study was 27.06 ± 5.27 y. Only 25 (6%) of 397 women had history of vaccination. Of 383 (92.06%) pregnant women who had rejected vaccination, 116 (30.28%) declared that they lacked information about influenza vaccination and 44 (11.48%) felt that they did not need vaccination. Concerns about the safety of influenza vaccination were reported by only 2 women (0.52%). Of the 25 (6%) pregnant women who were vaccinated against influenza, 15 (60%) accepted because of advice they received from persons other than physicians, 5 (20%) believed that influenza vaccination is necessary for everyone, and 3 (12%) accepted because of a history of frequent influenza virus infections in previous years.

Method: This questionnaire based study was conducted at obstetrics and maternity hospitals affiliated with Shiraz University of Medical Sciences, Shiraz, Iran. Pregnant women were interviewed individually and privately. SPSS was used for data analysis.

Conclusion: Most of the unvaccinated and vaccinated pregnant women lacked sufficient knowledge about influenza. Education of pregnant women about influenza vaccination and encouragement from physicians may have a remarkable effect on turning poor compliance into high flu vaccination uptake among pregnant women.




Licensed vaccines

SHORT REPORT

Does the Syrian population have to wait for the new generation of human papillomaviruses vaccine?

Ala-Eddin Al Moustafa, Amber Yasmeen, Lina Ghabreau and Nizar Akil
Pages 1867 - 1868
http://dx.doi.org/10.4161/hv.21973
Abstract | Full Text | PDF

We recently conducted several studies regarding the presence of high-risk HPVs in human cervical, colorectal and breast cancers in the Syrian population. Herein, we report that high-risk HPVs type 16, 18, 33, 45, 51, 52 and 58 are frequently present in colorectal cancer in this population. Therefore and based on previous studies and present data, we conclude that the most frequent high-risk HPV types, in the Syrian population, are 16, 18, 33, 35, 45, 51, 52 and 58. Thus, our data suggest that it will be useful to use the new generation of HPV vaccine to protect the Syrian population from high-risk HPVs and their associated cancers.

RESEARCH PAPERS

Protective efficacy of a recombinant BCG secreting antigen 85B/Rv3425 fusion protein against Mycobacterium tuberculosis infection in mice

Jiuling Wang, Yaqing Qie, Wei Liu and Honghai Wang
Pages 1869 - 1874
http://dx.doi.org/10.4161/hv.21817
Abstract | Full Text | PDF

In this study, the protective efficacy of a novel recombinant BCG strain co-expressing Ag85B and Rv3425 against Mycobacterium tuberculosis H37Rv was evaluated in mice. This rBCG::Ag85B-Rv3425 strain could provide similar or even better protective efficacy against M. tuberculosis challenge compared with BCG, as shown by no weight loss, significantly reduced lung:body weight ratios and lung bacteria load only at early time of infection. The results suggest that rBCG::Ag85B-Rv3425 could be a potential tuberculosis vaccine candidate for further study.

Open Access Article

Immunogenicity and safety results from a randomized multicenter trial comparing a Tdap-IPV vaccine (REPEVAX^®) and a tetanus monovalent vaccine in healthy adults: New considerations for the management of patients with tetanus-prone injuries

Henri Laurichesse, Ulrich Zimmermann, Florence Galtier, Odile Launay, Xavier Duval, Patrick Richard, Christine Sadorge and Benoit Soubeyrand
Pages 1875 - 1881
http://dx.doi.org/10.4161/hv.22083
Abstract | Full Text | PDF

In adults with a tetanus-prone injury, combined vaccines such as Tdap-IPV (REPEVAX^®) can boost immunity against several diseases simultaneously. This Phase IIIb, parallel-group, open-label trial compared antibody responses to Tdap-IPV and tetanus monovalent vaccine (TMV; Vaccin Tétanique Pasteur^® or Tetavax^®) against tetanus toxoid 10 and 28 d post-vaccination. Between July and December 2009, four centers in France and five in Germany recruited healthy adults who had received a tetanus-containing vaccine 5−10 y previously. Participants were randomized 1:1 to receive at the first visit a single dose (0.5 mL) of Tdap-IPV or TMV, with follow-up visits at Day 10 and Day 28. Outcomes: per protocol (PP) population immunogenicity at Day 10 (primary) and at Day 28 (secondary); safety throughout the study. Of 456 adults randomized, 223 received Tdap-IPV and 233 received TMV (PP population: 183 and 199 participants, respectively). All participants receiving Tdap-IPV and 99.0% receiving TMV had an anti-tetanus antibody concentration ≥ 0.1 IU/mL, confirming non-inferiority of Tdap-IPV to TMV (95% confidence interval of the difference: –1.2, 3.6). Number of adverse events reported was comparable in each group. Injection-site reactions were reported by 76.6% participants receiving Tdap-IPV and 74.6% receiving TMV. Systemic events (e.g., malaise, myalgia and headache) were reported in 47.7% and 39.7% of the Tdap-IPV and the TMV groups, respectively. Tdap-IPV is effective and well-tolerated for use in the management of tetanus-prone injuries in emergency settings in persons for whom a booster against diphtheria, pertussis and poliomyelitis is also needed. ClinicalTrials.gov identifier: NCT00928785. Research sponsored by Sanofi Pasteur MSD.




Special Focus: Meningococcal Vaccines and Disease

RESEARCH PAPERS

Open Access Article

A randomized study to assess the immunogenicity, antibody persistence and safety of a tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine in children aged 2–10 years

Timo Vesikari, Aino Forstén, Dominique Boutriau, Véronique Bianco, Marie Van der Wielen and Jacqueline M. Miller
Pages 1882 - 1891
http://dx.doi.org/10.4161/hv.22165
Abstract | PDF

Incidence of meningococcal diseases is high in children, and effective vaccines are needed for this age group. In this phase II, open, controlled study, 309 children aged 2–10 y from Finland were randomized (3:1) into two parallel groups to receive one dose of meningococcal ACWY-tetanus toxoid conjugate vaccine (ACWY-TT group; n = 231) or a licensed meningococcal ACWY polysaccharide vaccine (Men-PS group; n = 78). Serum bactericidal activity using rabbit complement (rSBA) was evaluated up to three years post-vaccination. Exploratory comparisons suggested that rSBA vaccine response rates and geometric mean titers (GMTs) for each serogroup at one month post-vaccination and rSBA GMTs for serogroups A, W-135 and Y up to three years post-vaccination were higher in the ACWY-TT compared with Men-PS group, but did not detect any difference between groups in terms of rSBA-MenC GMTs at three years post-vaccination; this is explained by the higher proportion of children from the Men-PS group who were excluded because they were re-vaccinated with a monovalent meningococcal serogroup C vaccine due to loss of protective antibody levels against this serogroup. Although there was a higher incidence of local reactogenicity in the ACWY-TT group, general and unsolicited symptoms reporting rates were comparable in both groups. This study showed that MenACWY-TT was immunogenic with a clinically acceptable safety profile in children aged 2–10 y. MenACWY-TT induced higher functional antibody titers for all serogroups, which persisted longer for serogroups A, W-135 and Y, than the MenACWY polysaccharide vaccine. This study has been registered at www.clinicaltrials.gov NCT00427908.

Open Access Article

Randomized trial to assess the immunogenicity, safety and antibody persistence up to three years after a single dose of a tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine in toddlers

Timo Vesikari, Aino Forstén, Dominique Boutriau, Véronique Bianco, Marie Van der Wielen and Jacqueline M. Miller
Pages 1892 - 1903
http://dx.doi.org/10.4161/hv.22166
Abstract | Full Text | PDF

Effective vaccines offering broad protection to toddlers, who are at high risk for invasive meningococcal disease, are needed. Here, the immunogenicity, safety and antibody persistence of the tetravalent meningococcal ACWY tetanus toxoid conjugate vaccine (MenACWY-TT) were evaluated in toddlers. Healthy participants aged 12 to 23 mo (n = 304) were randomized (3:1) to receive one dose of MenACWY-TT or a monovalent meningococcal serogroup C conjugate vaccine (MenC-CRM₁₉₇). Serum bactericidal activity was evaluated with assays using rabbit (rSBA) and human (hSBA) complement up to three years post-vaccination. MenACWY-TT was demonstrated to be non-inferior to MenC-CRM₁₉₇ in terms of immunogenicity to serogroup C, and the pre-specified immunogenicity criteria for serogroups A, W-135 and Y were met. Exploratory analyses suggested that rSBA geometric mean titers (GMTs), hSBA GMTs and proportions of toddlers with rSBA titers ≥ 1:128 and hSBA titers ≥ 1:4 and ≥ 1:8 were higher for all serogroups at one month post-vaccination with MenACWY-TT compared with MenC-CRM₁₉₇. At three years post-vaccination, at least 90.8% and 73.6% of MenACWY-TT recipients retained rSBA titers ≥ 1:8 for all serogroups and hSBA titers ≥ 1:4 for serogroups C, W-135 and Y, respectively, but the percentages of toddlers with hSBA titers ≥ 1:4 for serogroup A decreased to 21.8%. In both groups, grade 3 adverse events were infrequently reported and no serious adverse events were considered causally related to vaccination. These results suggest that one single dose of MenACWY-TT induces a robust and persistent immune response and has an acceptable safety profile in toddlers. This study has been registered at www.clinicaltrials.gov NCT00427908.

COMMENTARIES

Meningococcal vaccine: A new vaccine to combat meningococcal disease in India

Ramesh Verma and Pardeep Khanna
Pages 1904 - 1906
http://dx.doi.org/10.4161/hv.21666
Abstract | Full Text | PDF

Meningococcal meningitis is caused by Neisseria meningitidis, a gram-negative, aerobic, encapsulated diplococcus. Meningococci are divided into numerous serogroups based on the composition of their capsular polysaccharide (Ps) antigens. At least 13 serogroups have been described: A, B, C, D, 29E, H, I, K, L, W-135, X, Y and Z. Out of these 13, six (A, B, C, W135, X and Y) can cause epidemics. The incubation period averages 3–4 d (range 1–10 d), which is the period of communicability. Bacteria can be found for 2–4 d in the nose and pharynx, and for up to 24 h after starting antibiotics. N. meningitidis is a leading cause of meningitis worldwide and a significant public health problem and dreaded disease in most countries. Morbidity and mortality rates from the disease remain high. Apart from epidemics, at least 1.2 million cases of bacterial meningitis are estimated to occur every year, 135,000 of which are fatal – of these, ~500,000 and ~50,000 respectively are caused by meningococci. Many outbreaks of meningococcal meningitis have been documented, with major outbreaks mainly seen in large cities of northern, western and eastern India like New Delhi, Mumbai, Kolkata and northeastern states. In 2011, 245 people died in India, the vast majority (179) in West Bengal, while 467 and 341 people in 2009 and 2010 respectively died of this disease. The meningococcal conjugate vaccines (MCV) are preferred for reasons of immunogenicity and persistence of immunity but are unavailable in India. Only the quadrivalent and bivalent meningococcal Ps vaccines (MPV) are available in India. The quadrivalent MPV is preferred for Haj pilgrims, international travelers and students in that it provides protection against emerging W-135 and Y disease in these areas. A single-dose 0.5mL injection is recommended.

Meningococcal serogroup Y emergence in Europe: Update 2011

Michael Bröker, Susanne Jacobsson, Markku Kuusi, David Pace, Maria J. Simões, Anna Skoczynska, Muhamed-Kheir Taha, Maija Toropainen and Georgina Tzanakaki
Pages 1907 - 1911
http://dx.doi.org/10.4161/hv.21794
Abstract | Full Text | PDF

Neisseria meningitidis is differentiated into 12 distinct serogroups, of which A, B, C, W-135, X, and Y are medically most important and represent an important health problem in different parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. Recent epidemiological surveillance has indicated an increase of serogroup Y invasive meningococcal disease in some parts of Europe as shown in the epidemiological data for 2010 from various European countries previously published in this journal.¹ Here, data is reported indicating that the emergence of serogroup Y continued in 2011 in various regions of Europe. The average age of persons affected by N. meningitidis serogroup Y seems to have decreased in some countries in comparison to the previous decade.