Table of Contents

Volume 5, Issue 6

  June 2009

  Pages 363 - 434

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 Issue Catalogue (MARC XML)

EDITOR'S CORNER

Open Access Article

Letter from the Editor


Page 363
PDF




PORTRAIT OF A LEADING VACCINOLOGIST

Open Access Article

From therapeutic monoclonal antibodies to therapeutic vaccines for cancer

Neil L. Berinstein
Pages 364 - 367
PDF




MEETING REPORTS

Open Access Article

Investing in vaccines for developing countries: how public–private partnerships can confront neglected diseases

Mansour Yaïch
Pages 368 - 369
http://dx.doi.org/10.4161/hv.5.6.8172
Abstract | PDF

This commentary discusses the barrier of vaccine price on sustainable immunization programs in developing countries and offers examples of new mechanisms driven by public–private partnerships to overcome issues of affordability. These mechanisms include Advance Market Commitments with vaccine manufacturers, which take a demand-pull approach to ensure increased production of available vaccines or development of new vaccines for neglected diseases. A second approach applies a supply-push mechanism, such as technology transfer to developing-country manufacturers. A public–private partnership that set long-term, maximum public-sector pricing to increase access of a Japanese encephalitis vaccine for the developing world is highlighted. Lessons learned from this experience can be applied to address common obstacles to new vaccine introduction in resource-limited countries, including issues of affordability, manufacturing capacity, equity in access, and quality assurance.

Open Access Article

WVC Australia 2008: The next generation of vaccines

Ian D. Gust
Pages 370 - 372
http://dx.doi.org/10.4161/hv.5.6.7712
Abstract | PDF

The self-titled “World Vaccine Congress”, organized by the commercial conference organizer Terrapin, was held before a small audience in Sydney from October 13 – 15, 2008.




REVIEWS

Open Access Article

Recent advance in immunotherapies for Alzheimer disease, with special reference to DNA vaccination

Yoshio Okura and Yoh Matsumoto
Pages 373 - 380
http://dx.doi.org/10.4161/hv.5.6.7815
Abstract | PDF

Alzheimer’s disease (AD) is the most common cause of dementia characterized by progressive neurodegeneration.  Based on the amyloid cascade hypothesis, several immunotherapies for AD have been developed as curative treatment.  In 1999, Schenk et al. reported for the first time that amyloid beta (Aβ) deposits in AD model mice could be reduced by active vaccination with Aβ peptide.  Although clinical trials with the Aβ peptide were halted due to the development of meningoencephalitis in some treated patients, the vaccine therapy was judged to be effective on the basis of clinical and pathological analyses.  Passive immunization using humanized anti-Aβ monoclonal antibodies is also under clinical trials; however they have some problems to be solved.  As other strategies, DNA vaccines have been developed as immunotherapies for AD, which is simple, easily modified and can be administered without adjuvant.  DNA vaccines were developed by several groups including our laboratory, which induced Aβ reduction in AD model mice without side effects.  DNA vaccination may be open up new avenue of vaccine therapies for AD in the near future.

Open Access Article

Potential adjuvantic properties of innate immune stimuli

Hemamali J. Warshakoon, Jennifer D. Hood, Matthew R. Kimbrell, Subbalakshmi Malladi, Wen Yan Wu, Nikunj Shukla, Geetanjali Agnihotri, Diptesh Sil and Sunil A. David
Pages 381 - 394
http://dx.doi.org/10.4161/hv.5.6.8175
Abstract | PDF

Toll-like receptors (TLRs) are a family of conserved pattern recognition receptors (PRRs) that recognize pathogen associated molecular patterns and serve as primary sensors of the innate immune system. Ten members of the TLR family have so far been identified in the human genome. The ligands for these receptors are structurally highly conserved microbial molecules such as lipopolysaccharides (LPS) (recognized by TLR4), lipopeptides (TLR2 in combination with TLR1 or TLR6), flagellin (TLR5), single stranded RNA (TLR7 and TLR8), double-stranded RNA (TLR3), CpG motif-containing DNA (TLR9), and profilin present on uropathogenic bacteria (TLR 11). Complementing the TLRs are the nucleotide-binding domain (NOD), leucine rich repeat containing family (or Nod-like Receptors, NLRs), which detect muramylpeptides released from bacterial peptidoglycan (PGN) in the intracytoplasmic compartment, as well as the retinoic-acid-inducible protein 1 (RIG-I-like receptors; RLRs) which sense single-stranded RNA of viral origin. The activation of PRRs by their cognate ligands leads to production of inflammatory cytokines, up-regulation of MHC molecules and co-stimulatory signals in antigen-presenting cells as well as activating natural killer cells, in addition to priming and amplifying antigen-specific T-, and B-cell effector functions. Thus, these stimuli serve to link innate and adaptive immunity and can therefore be exploited as powerful adjuvants in eliciting both primary and anamnestic immune responses. This review summarizes what is currently known about the immunopotentiatory and adjuvantic activities of innate immune stimuli.




RESEARCH PAPERS

Open Access Article

Effect of a novel birth intervention and reminder-recall on on-time immunization compliance in high-risk children

Surabhi Vora, Lisa Verber, Sandra Potts, Tynisha Dozier and Robert S. Daum
Pages 395 - 402
http://dx.doi.org/10.4161/hv.5.6.7282
Abstract | PDF

Objectives: Profound racial/ethnic immunization rate disparities exist among young children in Chicago.  We created BIRTH PIP, a program combining immunization education at birth with ongoing reminder-recall, to achieve greater than 90% on-time adherence with AAP/ACIP immunization recommendations among inner-city children aged 0-35 months.  The study also examines the cost of this effort.


Study Design: Outreach workers met with post-partum mothers who were English speaking, Chicago residents and receiving Medicaid, to provide immunization education and determine a contact strategy.  Parents were reminded of each well-child appointment. Those missing appointments were re-contacted and rescheduled.  Home visits were made when there was no contact by phone and mail.  Enrollees and immunizations were tracked until all recommended immunizations were received.  On-time immunization rates were compared with city-wide immunization data.  Costs were calculated by assessing outreach worker effort and other programmatic costs.


Results: A total of 400 neonates were enrolled.  At all examined time points, on-time immunization rates exceeded city-wide data.  Of those completing the program, 92% of children had 100% compliance with prescribed immunizations by 24 months.  No child required follow-up past 29 months.  Retention was an important problem, primarily due to pre-set eligibility requirements.  Mean cost per child to complete recommended immunizations was $288.  Compliant families were less expensive to maintain.


Conclusions: BIRTH PIP is effective in improving immunization rates in underserved children.  Economies of scale will decrease the per child cost.  Preventing even a few cases of vaccine-preventable illness would likely render this initiative cost-effective.

Open Access Article

Immunization champions: Characteristics of general practitioners associated with better immunization delivery

Felicity Goodyear-Smith, Helen Petousis-Harris and Nikki Turner
Pages 403 - 411
http://dx.doi.org/10.4161/hv.5.6.8356
Abstract | PDF

Our aim was to describe characteristics of general practitioners (GPs) working in practices that achieve higher immunisation coverage and more timely delivery. We conducted computer-assisted telephone interviews with randomly selected GPs from randomly selected practices. Most GPs believed immunisation to be important and were confident about their knowledge of immunisation although assessment revealed their knowledge to be incomplete. A minority considered six weeks is too young to immunise. Greater GP knowledge and confidence in their knowledge was associated with higher practice immunisation coverage, whereas immunisation delivery was more timely at practices where GPs perceived parental access difficulties a barrier.

Open Access Article

Medical pediatric inpatients and outpatients are at risk of influenza and pneumococcal disease

F. Andrew I. Riordan and Shazia Adalat
Pages 412 - 413
http://dx.doi.org/10.4161/hv.5.6.7835
Abstract | PDF

Influenza and pneumococcal vaccines are recommended for certain risk groups. All children admitted to the children’s wards or attending children’s outpatients were studied for these risk factors. Risk factors for influenza were present in 78 (41%) of 193 admissions and 93 (27%) of 348 outpatients. Risk factors for pneumococcal infection were present in 22 (11.5%) admissions and 42 (12%) outpatients. Only 29 of these children had been given influenza (n=19) or pneumococcal (n=10) vaccines. Pediatricians could improve the coverage of influenza and pneumococcal vaccines by identifying children with risk factors in hospital discharge summaries and outpatient clinic letters.

Open Access Article

Immunogenicity, reactogenicity and safety of human rotavirus vaccine (RIX4414) in Indian infants

Anil Narang, Anuradha Bose, Anand Nilkanth Pandit, Phalguni Dutta, Gagandeep Kang, Sujit Kumar Bhattacharya, Sanjoy Datta, Suryakiran P.V., Andrée Delem, Htay Htay Han and Hans Ludwig Bock
Pages 414 - 419
http://dx.doi.org/10.4161/hv.5.6.8176
Abstract | PDF

Aim: This study was undertaken to assess the immunogenicity, reactogenicity and safety of two doses of an oral live-attenuated human rotavirus vaccine, strain RIX4414 (Rotarix™) in an Indian setting.
Patients and Methods: Healthy infants (N=363), approximately 8 weeks of age were enrolled to receive two doses of RIX4414 vaccine (n=182) or placebo (n=181) separated by one month. To assess the immune response, blood samples were taken before vaccination and one month post-dose 2 of RIX4414/placebo. Solicited symptoms were collected for 8-days post each dose and safety data was collected throughout the study.
Results: The seroconversion rate observed one month post-dose 2 in the RIX4414 group 58.3% [95% CI: 48.7; 67.4] was significantly higher when compared to the placebo group 6.3%; [95% CI: 2.5; 12.5]. The reactogenicity and safety profile was similar for both groups.
Conclusions: Two doses of RIX4414 (Rotarix™) were immunogenic, had a good safety profile and were well-tolerated when administered to healthy Indian infants.


Open Access Article

Epidemiology of typhoid and paratyphoid fever hospitalizations in Spain (1997-2005)

Ruth Gil, José Luis Álvarez, Camelia Gómez, Alejandro Álvaro and Ángel Gil
Pages 420 - 424
http://dx.doi.org/10.4161/hv.5.6.8228
Abstract | PDF

Background and Objective: This epidemiological survey was undertaken to estimate the burden of hospitalizations for typhoid and paratyphoid fever in Spain over a nine-year period (1997-2005).
Patients and Methods: Hospital discharges for typhoid or paratyphoid fever reported during a nine-year period in Spanish hospitals were obtained from the national surveillance system for hospital data, which is maintained by the Ministry of Health and covers more than 97% of Spanish hospitals.
Results: There were 1,106 hospitalizations for typhoid and paratyphoid fever during the study period. The annual hospitalization rate was 0.31 cases per 100,000 population. The mortality and case fatality rates were 0.003 per 100,000 population and 0.9%, respectively. The average length of hospitalization was 10.19 days. These hospitalizations impose an annual direct cost of € 334,000.
Conclusions Preventive measures are vital to reduce the occurrence of typhoid fever and avoid new outbreaks. Effective prevention would result in large cost savings to the National Health Care System.


Open Access Article

A comparison of immunogenicity and safety of indigenously developed liquid (DTwPHB-Hib) pentavalent combination vaccine (Shan 5) with Easyfive (Liq) and Tritanrix + Hiberix (Lyo) in Indian infants administered according to the EPI schedule

Raman Rao, Mandeep S. Dhingra, Sandeep Bavdekar, Narendra Behera, Subhash R. Daga, Ashok K. Dutta, Ritabrata Kundu, Padmanabha Maiya, Pravakar Mishra, Raju Shah, Sankaranarayan Shuba, Vinoo Tibrewala, Shaloo Pandhi and Arul Mani Rajamani
Pages 425 - 429
http://dx.doi.org/10.4161/hv.5.6.7816
Abstract | PDF

The study was planned to assess and compare the immune response and safety of an indigenous DTPwHB-Hib pentavalent liquid combination vaccine (Shan 5) with Easyfive and Tritanrix HB + Hiberix, the two available pentavalent combination vaccines. Four hundred infants were randomized to receive three doses of either Shan 5 or one of the two comparators. Antibody analysis was performed prior to and four to six weeks post third vaccine dose. Solicited local and systemic events upto three days and unsolicited adverse events in the 30 days follow up period after each dose were recorded. A total of 365 subjects completed the study. Four to six weeks after third dose, 98.32% of the subjects in Shan 5 group had seroprotective Anti PRP-T IgG antibody concentrations (≥0.15 µg/mL) as compared to 100% and 98.94% subjects in Tritanrix HB + Hiberix and Easyfive groups respectively. Seroprotective levels for Anti-HBs (≥10 mIU/mL) were observed in 97.77%, 97.83% and 98.94% subjects in Shan 5, Tritanrix HB + Hiberix and Easyfive groups respectively. Comparable immune responses were observed for the three other components (D, T and P) in all the groups. Four Serious Adverse Events (SAEs) were reported (three with Shan 5 and one with Easyfive), all unrelated to the respective vaccines. Most commonly reported adverse events in all the groups were pain at injection site, mild fever (< 103° F) and minor swelling at injection site. The study proved that Shan 5 was safe and immunogenic compared to the two other licensed vaccines.




COMMENTARY

Open Access Article

Influenza vaccination in children with cancer receiving chemotherapy

Susanna Esposito, Valerio Cecinati, Fabio Giovanni Russo and Nicola Principi
Pages 430 - 432
http://dx.doi.org/10.4161/hv.5.6.7942
Abstract | PDF

Influenza has a significant clinical impact on pediatric cancer patients because it causes frequent febrile episodes and respiratory tract infections, possibly severe complications, delays in chemotherapy administration, and even death, all of which supports the importance of prevention and the widespread use of influenza vaccination. Results from clinical studies show that influenza vaccination can be considered safe in children undergoing chemotherapy and, although weaker than in healthy children, the immune response seems to be sufficient in patients with leukemia or solid tumors even if it is less in children receiving chemotherapy than in those who are not. However, there is an urgent need for universally accepted guidelines concerning the type of vaccine that leads to the best immunological results, the number of administrations, and their timing in relation to the severity of immunosuppression and chemotherapy schedules. Such recommendations, together with a clear demonstration of vaccine efficacy, are also needed to increase influenza vaccination coverage in this high-risk category of patients.