Table of Contents

Volume 5, Issue 5

  May 2009

  Pages 277 - 360

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 Issue Catalogue (MARC XML)

EDITOR'S CORNER

Open Access Article

Letter from the Editor

Ronald W. Ellis and Eva Maria Riedmann
Page 277
http://dx.doi.org/10.4161/hv.5.5.8894
PDF




PORTRAIT OF A LEADING VACCINOLOGIST

Open Access Article

Can cell and gene therapy and vaccines be academically driven?

Susy Scholl
Pages 278 - 280
http://dx.doi.org/10.4161/hv.5.5.8826
PDF




MEETING REPORTS

Open Access Article

Mucosal immunity on the banks of the Duoro

Ed C. Lavelle, Yasmin Thanavala and Pearay Ogra
Pages 281 - 283
http://dx.doi.org/10.4161/hv.5.5.7801
Abstract | PDF

The beautiful city of Porto on the Portuguese Atlantic coast was the venue for ‘Modern Mucosal Vaccines, Adjuvants and Microbicides’ which was held from October 22-24, 2008.  The presence of a diverse audience from Academia, Industry and Public bodies indicated a growing interest in this field and on the basis of the data presented and the energy displayed, this discipline is in good shape and has the potential to deliver significant advances over the coming decade.

Open Access Article

Updates from the 18th National Immunization Conference for Health Care Workers: Manchester Conference Centre, December 2007


Martin J. Guppy and David N. Baxter
Pages 284 - 290
http://dx.doi.org/10.4161/hv.5.5.7410
Abstract | PDF

The annual National Immunization Conference (NIC) for Health Care Workers (HCW) was first held in 1989 with the aim of providing an update on current vaccine issues and new developments for any health worker involved with immunization. The conference has grown each year and continues to be of particular interest to Clinical Medical Officers, General Practitioners, Health Visitors, Practice Nurses, Occupational Health Practitioners, Paediatricians, Microbiologists, School Nurses and District Immunization Co-ordinators. Invited speakers are nationally and internationally renowned experts in their fields and there are usually around 150 delegates, mainly from the UK. The conference is organized by the University of Manchester Medical School and administration is carried out by the Stockport Foundation Trust Post-graduate Medical Department. Although the conference scientific program is largely concentrated on the use of vaccines as prophylactic agents, presentations around therapeutic immunization (exclusively in cancer treatment) have also been made recognizing that this is an area of growing interest and potential. The conference format combines presentations with extended periods of open discussion. The conclusions reached over the course of the conference are summarized here whilst conference video material for the past three conferences is freely available online as a learning resource (medicine.manchester.ac.uk).




REVIEWS

Open Access Article

Vaccines and vaccination strategies against human cutaneous leishmaniasis

Ifeoma Okwor and Jude Uzonna
Pages 291 - 301
http://dx.doi.org/10.4161/hv.5.5.7607
Abstract | PDF

One might think that the development of a vaccine against cutaneous leishmaniasis would be relatively straightforward because the type of immune response required for protection is known and natural immunity occurs following recovery from primary infection. However, there is as yet no effective vaccine against the disease in humans. Although vaccination in murine studies has yielded promising results, these vaccines have failed miserably when tested in primates or humans. The reasons behind these failures are unknown and remain a major hurdle for vaccine design and development against cutaneous leishmaniasis. In contrast, recovery from natural, deliberate or experimental infections results in development of long-lasting immunity to re-infection. This so called infection-induced resistance is the strongest anti-Leishmania immunity known. Here, we briefly review the different approaches to vaccination against cutaneous leishmaniasis and argue that vaccines composed of genetically modified (attenuated) parasites, which induce immunity akin to infection-induced resistance, may provide best protection against cutaneous leishmaniasis in humans.

Open Access Article

Vaccines targeting IgE in the treatment of asthma and allergy

Zhikang Peng
Pages 302 - 309
http://dx.doi.org/10.4161/hv.5.5.7442
Abstract | PDF

Allergic diseases including asthma are characterized by an increase of serum IgE levels. Since IgE was discovered in 1966, it has been considered to be the most important biological target in the treatment of allergy and asthma. Indeed, recent studies reveal that IgE, through its high affinity IgE receptors (FcεRI), is now considered a critical regulator of Th2 responses. This is supported by the great success of the anti-IgE monoclonal antibody (mAb) in the treatment of allergy and asthma. Nonetheless, adverse reactions such as anaphylaxis, urticaria, and serum sickness have been reported with this therapy and repeated injections at extremely high costs are required to maintain effectiveness.
To overcome these disadvantages, a new strategy using vaccines against IgE that may offer long-term efficacy with fewer adverse effects is being investigated. This article reviews IgE’s role in allergy and asthma, currently used anti-IgE mAb omalizumab, and the advantages, types, effectiveness, and development stages of vaccines against IgE. This review also discusses concerns with the vaccine strategy.




RESEARCH PAPERS

Open Access Article

Safety and immunogenicity of diphtheria-tetanus-pertussis vaccine and hepatitis B vaccine as a new tetravalent combination (DTwP/HB) administered alone and at separate sites (DTwP & HB) including comparison with standard commercially available combination vaccine in Indian infants 6-14 weeks of age

Hitt J. Sharma, Ashok K. Dutta, Surekha M. Joshi, Sushma Malik, Subodh Bhardwaj, Gajanan S. Namjoshi and Sameer S. Parekh
Pages 310 - 314
http://dx.doi.org/10.4161/hv.5.5.6909
Abstract | PDF

An open, comparative study was conducted at two tertiary care hospitals in India to assess immunogenicity and reactogenicity following administration of the DTwP/HB combination vaccine (Q-Vac) alone and DTwP and HB (Genevac B) vaccines at separate sites. These vaccines manufactured by Serum Institute of India Ltd (SIIL), Pune were compared with DTwP/HB vaccine (Tritanrix HB) manufactured by Glaxo SmithKline (GSK) in infants aged 6 - 14 weeks. The sample size comprised 447 infants who received DTwP/HB vaccine (Group A – 150, SIIL) or DTPw & HB (Group B – 147, SIIL) vaccines at separate sites or DTPw/HB vaccine (Group C – 150, GSK), in a dose of 0.5 ml intra-muscularly. Pre and postvaccination IgG antibodies were determined by ELISA. Postvaccination, in Group A sero-protection was 99.3%, 100%, 96%, and 100% to Diphtheria, Tetanus, Pertussis and HBs components respectively. In Group B (n=147) it was 98.6%, 100%, 95.9% and 99.3% and in Group C (n=150), it was 96%, 99.3%, 93.3% and 98.6% to D, T, P and HBs component of the vaccine. Postvaccination, geometric mean titres for each component were comparable across three groups by analysis of variance (ANOVA). Adverse events observed were within the range quoted in literature and no Serious Adverse Event (SAE) was observed. Reactogenicity profile in all three groups was comparable. Q-Vac vaccine manufactured by SIIL was found to be safe and immunogenic. Hepatitis B component did not interfere with the immune response to DTwP components of the vaccine.

Open Access Article

Safety of Tdap-IPV given one month after Td-IPV booster in healthy young adults: A placebo-controlled trial

Jean Beytout, Odile Launay, Nicole Guiso, Anne Fiquet, Martine Baudin, Patrick Richard, Charles Baptiste and Benoît Soubeyrand
Pages 315 - 321
http://dx.doi.org/10.4161/hv.5.5.6911
Abstract | PDF

Background: In France, the only vaccines available for use as a pertussis booster in adults are combined vaccines containing adsorbed tetanus, diphtheria (adult formulation), acellular pertussis and inactivated poliovirus (Tdap-IPV). Adults may require a pertussis booster relatively soon after having received vaccines containing tetanus-diptheria antigens (Td)(occupational or familial circumstances as new job, childbirth in recent past or future), although the safety of Tdap-IPV when administered soon after vaccination with Td is undocumented.

Methods: In this randomized, double-blind, multi-centre study, we assessed the safety of Tdap-IPV administered 1 month after vaccination with tetanus, diphtheria (adult formulation), inactivated poliovirus vaccination (Td-IPV) in healthy adults vaccinated according to the French vaccination calendar (seven tetanus-diphtheria vaccinations by age 18 years). Subjects received either Td-IPV (n = 249) or placebo (n = 251) followed 1 month later by Tdap-IPV. Any adverse events (AEs) were recorded.

Results: The safety of Tdap-IPV was similar when Tdap-IPV vaccine was administered 1 month after either Td-IPV or placebo: at 7 days, 85.1% versus 93.4% subjects reported at least one reaction at the injection site, mainly pain (82.6% versus 92.1%); 40.5% versus 45.0%, at least one systemic AE (mainly headache: 26.4% versus 26.0%); fever concerned 1.7% of both groups. No serious vaccine-related AEs were reported. Both safety profiles corresponded to documented product characteristics.

Conclusions: Tdap-IPV may be administered to adults 1 month after Td-IPV without exacerbating post-vaccination side-effects.

Open Access Article

Towards development of stable formulations of a live attenuated bacterial vaccine: A preformulation study facilitated by a biophysical approach

Yuhong Zeng, Haihong Fan, Gary Chiueh, Binh Pham, Russ Martin, David Lechuga-Ballesteros, Vu L. Truong, Sangeeta B. Joshi and C. Russell Middaugh
Pages 322 - 331
http://dx.doi.org/10.4161/hv.5.5.7559
Abstract | PDF

Development of optimal formulation conditions stabilizing live attenuated bacterial vaccines is impeded by traditional methods used for viability measurement. To facilitate preformulation studies of such vaccines, spectroscopic techniques capable of providing real-time and high throughput information have been employed to obtain a global stability profile for a live attenuated Ty21a bacterial typhoid vaccine over a wide range of pH (4 to 8) and temperature (10 to 85°C). Using the data obtained from fluorescence and circular dichroism techniques, an empirical phase diagram (EPD) has been subsequently constructed, which suggests that Ty21a cells exist in at least 4 apparent physical phases related to different viability states, with the most stable phase at pH 6 and 7 at temperatures below 30°C.  A slightly basic pH (pH 8) appears to decrease the fluidity of the cell membrane, whereas acidic pH conditions are detrimental to membrane integrity over the entire temperature range. Based on the above stability profile, a fluorescence-based high throughput screening assay has been developed to test the stabilizing effects of various compounds at different concentrations. Amongst other promising stabilizers, 10% sucrose and 0.15 M glutamic acid display the greatest protective effects, with an increase of about 10°C in the transition temperature of Ty21a cells. Preliminary studies have also been performed on foam dried formulations as an alternative approach to further stabilize Ty21a cells. The data show that 10% sucrose and trehalose both increase the in-process and storage stabilities of the cells.

Open Access Article

Safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for cervical cancer prevention: A pooled analysis of 11 clinical trials

Dominique Descamps, Karin Hardt, Bart Spiessens, Patricia Izurieta, Thomas Verstraeten, Thomas Breuer and Gary Dubin
Pages 332 - 340
http://dx.doi.org/10.4161/hv.5.5.7211
Abstract | PDF

A pooled analysis of the safety of the human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine Cervarix™ (GlaxoSmithKline) was performed in a cohort of almost 30000 girls and women aged ≥10 years, 16142 who received at least one dose of the HPV-16/18 vaccine and 13811 who received one of three controls [Al(OH)3 or hepatitis A vaccine (720 or 360 EU)]. Data are available for a total of 45988 vaccine doses. Solicited local and general symptoms were recorded for 7 days after each dose. Serious adverse events (SAEs), pregnancies, medically significant conditions (MSCs) and new onset of chronic diseases (NOCDs), including new onset of autoimmune diseases (NOADs), were proactively monitored. Data were analyzed by vaccine group according to age (10–14, 15–25 and >25 years) and reporting period (Months 0–7, Months 7–12 and >Month 12). Rates of solicited local and general symptoms were higher in the HPV-16/18 vaccine group than in the control groups. However, compliance with the 3-dose schedule was high and did not differ between groups (93.4% for HPV-16/18 vaccine group versus 92.5% for pooled controls). No clinically relevant differences were seen between the HPV-16/18 vaccine and pooled control groups in rates of SAEs (2.8% versus 3.1%), MSCs (19.4% versus 21.4%), NOCDs (1.7% in both groups) or NOADs (0.4% versus 0.3%). Similarly, no differences in pregnancy outcomes or rates of withdrawals due to AEs or SAEs were observed between groups. In conclusion, analysis of this large database shows the HPV-16/18 AS04-adjuvanted cervical cancer vaccine to have a favorable safety profile in women of all ages.

Open Access Article

Antibodies to tetanus, diphtheria and pertussis among healthy adults vaccinated according to the French vaccination recommendations

Odile Launay, Christine Toneatti, Claire Bernède, Elisabeth Njamkepo, Karine Petitprez, Annie Leblond, Sylvie Larnaudie, Catherine Goujon, Marie-Noelle Ungeheuer, Faïza Ajana, Christian Raccurt, Jean Beytout, Christian Chidiac, Damien Bouhour, Didier Guillemot and Nicole Guiso
Pages 341 - 346
http://dx.doi.org/10.4161/hv.5.5.7575
Abstract | PDF

In this sero-epidemiological study, we investigated humoral immunity to three vaccine-preventable diseases—tetanus, diphtheria and pertussis—among 331 adults (aged 18–60 years) attending vaccination centres for travellers and who had been vaccinated according to national recommendations in France. Serological results showed that the percentage of subjects with antibodies to diphtheria and tetanus decreases with age. Results also confirmed surveillance data on vaccination in France, with 7.6% of the study population (13.4% of those aged 18–29 years) having recently acquired a pertussis infection. These results confirm the importance of following French recommendations for regular boosters for tetanus and diphtheria among adults. They also indicate the need for better implementation of the current recommendations for pertussis-vaccine boosters in adults.

Open Access Article

Proteomic study via a non-gel based approach of meningococcal outer membrane vesicle vaccine obtained from strain CU385: A road map for discovering new antigens

Jeovanis Gil, Lázaro H. Betancourt, Gretel Sardiñas, Daniel Yero, Olivia Niebla, Maité Delgado, Darien García, Rolando Pajón, Aniel Sánchez, Luis J. González, Gabriel Padrón, Concepción Campa, Franklin Sotolongo, Ramón Barberá, Gerardo Guillén, Luis Herrera and Vladimir Besada
Pages 347 - 356
http://dx.doi.org/10.4161/hv.5.5.7367
Abstract | PDF

This work presents the results from a study of the protein composition of outer membrane vesicles from VA-MENGOC-BC^® (Finlay Institute, Cuba), an available vaccine against serogroup B Neisseria meningitidis. Proteins were identified by means of SCAPE, a 2DE-free method for proteome studies. More than one hundred proteins were detected by tandem liquid chromatography-mass spectrometry analysis of fractions enriched in peptides devoid of histidine or arginine residues, providing a detailed description of the vaccine. A bioinformatic analysis of the identified components resulted in the identification of 31 outer membrane proteins and three conserved hypothetical proteins, allowing the cloning, expression, purification and immunological study of two of them (NMB0088 and NMB1796) as new antigens.




COMMENTARY

Open Access Article

Viral hepatitis: Some reflections on a personal journey

Ian Gust
Pages 357 - 360
http://dx.doi.org/10.4161/hv.5.5.8234
Abstract | PDF

The pathway to understanding a new field is often more fraught with issues than it appears from later accounts.  The series of coincidences that led to my involvement in the field of viral hepatitis and the circuitous pathway leading to the development of the first hepatitis A vaccine is described from a personal perspective.