Table of Contents

Volume 7, Issue 1

  January 2011

  Pages 1 - 131

Special Focus on Type-1 Diabetes Vaccines

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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 1
http://dx.doi.org/10.4161/hv.7.1.14923
Abstract | PDF




Open Access Article

Human Vaccines awards Top Reviewer of the Year

Ronald W. Ellis and Eva M. Riedmann
Pages 2 - 5
http://dx.doi.org/10.4161/hv.7.1.14926
Abstract | PDF







NEWS, POLICY AND PROFILES

Open Access Article

News

Eva M. Riedmann
Pages 6 - 9
http://dx.doi.org/10.4161/hv.7.1.14924
Abstract | PDF

Bavarian in talks with potential Prostvac partners Sanofi Pasteur advances intradermal flu vaccine candidate WHO launches cheap meningitis vaccine in Africa Bionor continues development of its HIV vaccine Vacc-4x New way to predict dominant seasonal flu strain Promising Phase II results for Celldex brain cancer vaccine Breakthrough in cancer vaccine research FDA Advisory Committee Supports Approval of GARDASIL® for prevention of anal cancer and AIN in both men and women

Open Access Article

A universal influenza vaccine: Where are we in the pursuit of this “Holy Grail”?

Wayne Rudolph and Tamar Ben Yedidia
Pages 10 - 11
http://dx.doi.org/10.4161/hv.7.1.14925
Abstract | PDF







MEETING REPORT

Open Access Article

Second National Immunization Congress 2010: Addressing vaccine financing for the future in the US

Angela K. Shen, Elizabeth Sobzcyk, Anna Buchanan, Lauren Wu and Sarah Duggan-Goldstein
Pages 12 - 18
http://dx.doi.org/10.4161/hv.7.1.13949
Abstract | PDF

At the 2nd National Immunization Congress held in Chicago, IL, from August 31-September 2, 2010, partners from government, provider groups, academia, and manufacturers gathered to discuss the progress made and the future of financing child, adolescent, and adult vaccines. The meeting is a continuation of a solution-oriented vaccine financing dialogue held in February 2007 at the 1st Immunization Congress. The need for this forum arose from concerns that increased costs of immunization could hinder the ability of current financing and delivery systems to maintain access without financial barriers. Preventive care and additional financial coverage for vaccines are key points in federal health reform but some populations, especially adolescents and adults, could continue to experience challenges in accessing vaccines. Congress participants discussed adequate reimbursement in the public and private sectors for vaccine delivery and the potential financial resources, data, and infrastructure needed to increase vaccine uptake in the US. Participants agreed that partners from all sectors – manufacturers, providers, public health, employers, payors, insurers, and consumers – will collectively need to leverage their efforts to address financial gaps not covered by health care reform law to ensure the preventive benefits of vaccines are fully realized for all Americans.




SPECIAL FOCUS REVIEWS

Open Access Article

Type 1 diabetes vaccine development: Animal models vs. humans

Tobias Boettler and Matthias von Herrath
Pages 19 - 26
http://dx.doi.org/10.4161/hv.7.1.12641
Abstract | PDF

The loss of tolerance towards self-antigens on pancreatic β-cells is the hallmark of type 1 diabetes that ultimately causes destruction of the islets of Langerhans, loss of blood glucose control and severe long-term complications. One major aspect that contributes to the emergence of autoreactivity may be the interplay of several microbial agents with the immune system that, depending on its nature, may promote autoreactivity or confer protection. Since there is no curative treatment available that can be safely administered to the increasing number of patients suffering from this disease, the development of a vaccine that prevents autoreactivity or re-introduces immune regulation once autoreactivity occurs is of great interest, particularly because other treatment options almost entirely depend on general immunosuppression. Here, we will discuss recent developments in vaccine discovery and, since a majority of the available information is derived from animal models, will focus on the question, how these observations may be translated to a therapy for human type 1 diabetes.

Open Access Article

Genetic vaccination for re-establishing T-cell tolerance in type 1 diabetes

Mark C. Johnson, Bo Wang and Roland Tisch
Pages 27 - 36
http://dx.doi.org/10.4161/hv.7.1.12848
Abstract | PDF

Type 1 diabetes (T1D) is a T-cell mediated autoimmune disease resulting in the destruction of the insulin-secreting β cells. Currently, there is no established clinical approach to effectively suppress long-term the diabetogenic response. Genetic-based vaccination offers a general strategy to reestablish β-cell specific tolerance within the T-cell compartment. The transfer of genes encoding β-cell autoantigens, anti-inflammatory cytokines and/or immunomodulatory proteins has proven to be effective at preventing and suppressing the diabetogenic response in animal models of T1D. The current review will discuss genetic approaches to prevent and treat T1D with an emphasis on plasmid DNA- and adeno-associated virus-based vaccines.

Open Access Article

Multifunctional dendritic cell-targeting polymeric microparticles: Engineering new vaccines for type 1 diabetes

Benjamin G. Keselowsky, Chang Qing Xia and Michael Clare-Salzler
Pages 37 - 44
http://dx.doi.org/10.4161/hv.7.1.12916
Abstract | Full Text | PDF




Open Access Article

Does immune-tolerance treatment with Alum-formulated GAD65 protect insulin-production in the pancreatic islet β cells?

Helena Elding Larsson and Åke Lernmark
Pages 45 - 49
http://dx.doi.org/10.4161/hv.7.1.14488
Abstract | PDF

Type 1 diabetes is a serious chronic disease in which the pancreatic islet beta cells are destroyed by autoimmunity specifically directed to intracellular autoantigens. Still undefined environmental factors are likely to initiate the disease process. One of the autoantigens is glutamic acid decarboxylase (GAD65) and attempts are made to induce immunological tolerance against this autoantigen. Alum-formulated GAD65 (Diamyd^®) has been given subcutaneously in two injections with one month apart to recent onset type 1 diabetes patients with positive GAD65 autoantibodies. The injections were found to preserve residual β-cell function without treatment related serious adverse events. Phase III studies in children with recent onset type 1 diabetes are ongoing along with a study (DIAPREV-IT) aimed at testing whether Diamyd^® may prevent the clinical onset of diabetes in non-diabetic children with GAD65 autoantibodies and at least one more islet autoantibody. Future studies may include investigation of Diamyd^® in combination with other immunomodulating autoantigens.

Open Access Article

Regulatory and policy issues for T1DM immunotherapy

Alexander Fleming
Pages 50 - 55
http://dx.doi.org/10.4161/hv.7.1.14527
Abstract | PDF

The development of immunotherapies for T1DM has lagged the development T2DM drugs, but with more clarity around regulatory requirements, large pharmaceutical companies have recently entered the field to support late stage programs. This clarity around regulatory expectations has emerged because of the convergence among regulators and clinical experts in how efficacy of these therapies should be assessed. The key agreement is that the primary efficacy endpoint for treatments directed at the underlying autoimmune cause of T1DM should be endogenous insulin secretion as reflected by standardized C-peptide measurements. Important secondary endpoints include glycemic control, total daily insulin dose, and hypoglycemia rates. Most T1DM therapeutic development efforts are directed at new onset disease, which represents a small proportion of the entire T1DM population. A new frontier in T1DM therapeutic development is emerging around combination treatment of established T1DM, a population that far outnumbers those with new onset T1DM. Fully effective therapies of new onset or established T1DM will almost certainly require a combination of two or more therapies. A T1DM prevention vaccine will not be feasible until after extensive experience with the agent as a treatment of new onset and/or established T1DM.




SHORT REPORT

Open Access Article

H1N1 influenza A outbreak among young medical staff members who received single dose of non-adjuvanted split-virion 2009 H1N1 vaccine

Mamiko Ohara, Masaharu Tsubokura, Hosokawa Naoto , Masahiro Kami and Takahiro Mochizuki
Pages 56 - 57
http://dx.doi.org/10.4161/hv.7.1.13459
Abstract | PDF

We experienced an H1N1 influenza A outbreak among medical staff members who had received a vaccination. To investigate the preventive effects of the H1N1 influenza vaccine on the H1N1 influenza A infection, we examined the data on the medical staff members and patients with confirmed H1N1 influenza A or influenza-like illness retrospectively. Approximately half of the young individuals under 30 years of age developed H1N1 influenza A, while the diagnosis was established in 3% of medical staff over the age of 30 and 0.9% of patients with a median age of 67. The mechanism for association between age and the risk of H1N1 infection is unclear; however, it might have been associated with an age-related increase in the prevalence of neutralizing antibody titers against the 2009 H1N1 influenza A as indicated by previous reports. This study showed that current Japanese H1N1 influenza A vaccine program using one dose of non-adjuvant split-virion 2009 H1N1 vaccine with 7.5 μg hemagglutinin had a limited preventive effect on H1N1 influenza A infection in adults under 30 years of age.




RESEARCH PAPERS

Open Access Article

Assessment of the safety, tolerability and kinetics of the immune response to A/H1N1v vaccine formulations with and without adjuvant in healthy pediatric subjects from 3 through 17 years of age

Adriano Arguedas, Carolina Soley, Arturo Abdelnour, Victor Sales, Kelly Lindert, Giovanni Della Cioppa and Ralf Clemens
Pages 58 - 66
http://dx.doi.org/10.4161/hv.7.1.13411
Abstract | PDF

Background: The recent global A/H1N1v pandemic led to major efforts to develop effective vaccines against the novel virus, while global demand and limited production capacity focused attention on dose sparing and schedules. Methods: An open-label phase III study of immunogenicity and safety of novel A/H1N1v vaccines included 392 Costa Rican children in two pediatric cohorts (3–8 and 9–17 years). They received two doses, of either an MF59®-adjuvanted formulation containing 7.5 μg antigen or non-adjuvanted formulations containing 15 or 30 μg antigen, three weeks apart. Immunogenicity was assessed as hemagglutination inhibition (HI) titers using the CBER licensure criteria. Results: All three vaccines elicited immune responses in 9–17 year-olds meeting CBER criteria three weeks after one dose; responses were not enhanced by second dose. In 3–8 year-olds only the adjuvanted vaccine met the CBER criteria after one dose, but all three vaccines met criteria after second dose. All vaccines were well tolerated; no related Serious Adverse Events (SAE) and few severe solicited reactions were reported. MF59-adjuvanted vaccine was associated with more reports of injection site pain and tenderness and overall systemic solicited reactions, most notably in older subjects, all of which decreased after the second dose. Conclusion: One dose of non-adjuvanted A/H1N1v vaccine is adequate in 9–17 year-olds, but younger children require either one dose of MF59-adjuvanted vaccine or two doses of non-adjuvanted vaccine to achieve protective titers. Enhanced immunogenicity with MF59 is associated with a small increase in reactogenicity, but no safety issues.

Open Access Article

Correlates of receiving recommended adolescent vaccines among adolescent females in North Carolina

Paul L. Reiter, Annie-Laurie McRee, Sami L. Gottlieb and Noel T. Brewer
Pages 67 - 73
http://dx.doi.org/10.4161/hv.7.1.13500
Abstract | PDF

Background. Immunization is a successful and cost-effective method for preventing disease, yet many adolescents do not receive recommended vaccines. We assessed correlates of uptake of three vaccines (tetanus booster, meningococcal, and human papillomavirus [HPV] vaccines) recommended for adolescent females. Methods. We examined cross-sectional data from 647 parents of 11-20 year-old females from North Carolina who completed the Carolina HPV Immunization Measurement and Evaluation (CHIME) Project follow-up survey in late 2008. Analyses used ordinal and binary logistic regression. Results. Only 17% of parents indicated their daughters had received all three vaccines. Eighty-seven percent of parents indicated their daughters had received tetanus booster vaccine, 36% reported vaccination against meningococcal disease, and 36% reported HPV vaccine initiation. Daughters aged 13-15 years (OR=1.70, 95% CI: 1.09–2.64) or 16-20 years (OR=2.28, 95% CI: 1.51–3.44) had received a greater number of these vaccines compared to daughters aged 11-12 years. Daughters who had preventive care visits in the last year (OR=4.81, 95% CI: 3.14–7.34) or whose parents had at least some college education (OR=1.90, 95% CI: 1.29–2.80) had also received a greater number of these vaccines. Conclusions. Few daughters, particularly 11-12 years olds, had received all three vaccines recommended for adolescent females. Ensuring annual preventive care visits and increasing concomitant administration of adolescent vaccines may help increase vaccine coverage.

Open Access Article

Immunogenicity of a human rotavirus vaccine (RIX4414) after storage at 37°C for seven days

Angkool Kerdpanich, Kulkanya Chokephaibulkit, Veerachai Watanaveeradej, Nirun Vanprapar, Sriluck Simasathien, Nopaorn Phavichitr, Hans Ludwig Bock, Silvia Damaso, Yanee Hutagalung and Htay-Htay Han
Pages 74 - 80
http://dx.doi.org/10.4161/hv.7.1.13412
Abstract | PDF

Aim: The lyophilized formulation of the human rotavirus vaccine, RIX4414 (RotarixTM), is recommended to be stored at 2°C–8°C for optimal immunogenicity. In some settings with inadequate infrastructure for vaccine storage, unforeseen circumstances may cause cold chain breakage, resulting in the vaccine to be left at ambient temperatures. This study evaluated the heat stability of lyophilized RIX4414 vaccine in terms of immunogenicity when stored at tropical room temperature (37°C) for 7 days before reconstitution.
Results: There was no statistically significant difference detected between RIX4414 vaccine stored at 2°C–8°C (Group RIX4414_control, n = 171) and that stored at 37°C for 7 days (Group RIX4414_37°C, n = 47) in terms of seroconversion rate and vaccine take. The anti-rotavirus IgA seroconversion rate 2 months post-Dose 2 was 84.7% (95% CI: 78.1%–90%) and 87.8% (95% CI: 73.8%–95.9%) in Groups RIX4414_control and RIX4414_37°C, respectively. None of the 25 infants in placebo group seroconverted. The vaccine take in the respective vaccine groups were 88% (95% CI: 82.1%–92.5%) and 93.5% (95% CI: 82.1%–98.6%) and Geometric Mean Concentrations (GMCs) were 134.4 U/mL (95% CI: 104.5–172.9) and 163.7 U/mL (95% CI: 98.9–271.1).
Methods: Healthy infants aged 6–12 weeks, received two oral doses of either the RIX4414 vaccine stored at 2°C–8°C, RIX4414 vaccine stored at 37°C for 7 days or placebo, according to a 0, 2 month schedule. Seroconversion rates in terms of anti-rotavirus IgA antibody levels (cut off: ≥20 U/mL by ELISA), anti-rotavirus IgA antibody GMCs and vaccine take were calculated 2 months post-Dose 2.
Conclusion: Lyophilized RIX4414 vaccine stored at 37°C for 7 days before reconstitution has similar immunogenicity as the vaccine stored at 2°C–8°C. These results supported the use of RIX4414 in settings where the vaccine might be exposed to higher than the recommended storage temperatures.

Open Access Article

Immunologic non-inferiority of a newly licensed inactivated trivalent influenza vaccine versus an established vaccine: A randomized study in US adults

James D. Campbell, Christopher V. Chambers, Rebecca C. Brady, Michael C. Caldwell, Nathan L. Bennett, Marc A. Fourneau, Varsha K. Jain and Bruce L. Innis
Pages 81 - 88
http://dx.doi.org/10.4161/hv.7.1.13553
Abstract | PDF

A trivalent inactivated influenza vaccine (Fluarix^™, GlaxoSmithKline Biologicals) was licensed under US accelerated approval regulations. We performed a randomized, observer-blind, post-approval study to demonstrate its immunological non-inferiority versus an established US-licensed vaccine (primary endpoint). Adult (including elderly) subjects received a single injection of newly-licensed vaccine (n=923) or established vaccine (n=922). Serum hemagglutination-inhibition titers were determined pre-vaccination and 21-28 days after vaccination. Non-inferiority was assessed by post-vaccination geometric mean titer (GMT) ratio (upper 95% confidence interval [CI] ≤1.5) and difference in seroconversion rate (upper 95% CI ≤0.1) for all three vaccine strains. Safety was monitored for 6 months. The newly-licensed vaccine was non-inferior to the established vaccine in all subjects (≥18 years) and in elderly subjects (≥65 years). Adjusted GMT ratios (established/newly-licensed) against the H1N1, H3N2 and B strains were 0.65 (95% CI: 0.58, 0.73), 0.93 (0.83, 1.04) and 1.13 (1.03, 1.25) for all subjects and 0.75 (0.67, 0.85), 0.95 (0.82, 1.09) and 1.13 (1.00, 1.27) for elderly subjects. Corresponding values for the differences in seroconversion rate (established minus newly-licensed) were -0.12 (-0.16, -0.07), -0.02 (-0.06, 0.03) and 0.01 (-0.04, 0.06) for all subjects and -0.11 (-0.16, -0.05), -0.02 (-0.07, 0.04) and 0.02 (-0.04, 0.08) for elderly subjects. The most common adverse events with both vaccines were injection site pain, fatigue and headache, and no serious adverse events or deaths were considered related; there were no clinically relevant differences between the vaccines. In conclusion, the newly-licensed vaccine was well tolerated and immunologically non-inferior to the established vaccine for all three vaccine strains in the whole population and the elderly.

Open Access Article

Seasonal and 2009 H1N1 influenza vaccine uptake, predictors of vaccination, and self-reported barriers to vaccination among secondary school teachers and staff

Lisa M. Gargano, Julia E. Painter, Jessica M. Sales, Christopher Morfaw, LaDawna M. Jones, Dennis Murray, Gina M. Wingood, Ralph J. DiClemente and James M. Hughes
Pages 89 - 95
http://dx.doi.org/10.4161/hv.7.1.13460
Abstract | PDF

Objective: Teachers, like healthcare workers, may be a strategic target for influenza immunization programs. Influenza vaccination is critical to protect both teachers and the students they come into contact with. This study assessed factors associated with seasonal and H1N1 influenza vaccine uptake among middle- and high-school teachers. Methods: Participants were recruited from two counties in rural Georgia. Data were collected from surveys in September 2009 and May 2010. Multivariate logistic regression was used to assess the association between teachers’ attitudes toward seasonal and H1N1 influenza vaccination and vaccine uptake. Results: Seventy-eight percent of teachers who planned to receive seasonal influenza vaccine and 36% of those who planned to receive H1N1 influenza vaccine at baseline reported that they did so. Seasonal vaccine uptake was significantly associated with perceived severity (odds ratio [OR] 1.57, P=0.05) and self-efficacy (OR 4.46, P=0.006). H1N1 vaccine uptake was associated with perceived barriers (OR 0.7, P=0.014) and social norms (OR 1.39, P=0.05). The number one reason for both seasonal and H1N1 influenza vaccine uptake was to avoid getting seasonal/H1N1 influenza disease. The number one reason for seasonal influenza vaccine refusal was a concern it would make them sick and for H1N1 influenza vaccine refusal was concern about vaccine side effects. Conclusions: There is a strong association between the intention to be vaccinated against influenza (seasonal or 2009 H1N1) and actual vaccination uptake. Understanding and addressing factors associated with teachers’ influenza vaccine uptake may enhance future influenza immunization efforts.

Open Access Article

Cost of acute hospitalization and post-discharge follow-up care for meningococcal disease in the US

Keith L. Davis, Derek Misurski, Jacqueline M. Miller, Timothy J. Bell and Bela Bapat
Pages 96 - 101
http://dx.doi.org/10.4161/hv.7.1.13692
Abstract | PDF

The combined costs of acute hospitalization and post-discharge follow-up care in patients with meningococcal disease have not been widely documented. In this study, data were retrospectively analyzed from three large databases of hospital discharge records and commercial insurance claims in the US. Cases of meningococcal disease were defined as admissions with an ICD-9-CM diagnosis code in the range of 036.x. From the 2005 HCUP Nationwide Inpatient Sample, 349 (weighted N=1,710) meningococcal-related hospitalizations were identified with a mean facility cost (in 2009 dollars) of $19,526 per admission. Similar estimates ($18,119 and $20,066, respectively) were obtained from 268 admissions identified in the LifeLink (formerly PharMetrics) database during 1999-2007 and from 1,058 hospitalizations in the Perspective Comparative Database (PCD) during 2000-2007. Using insurance claims from LifeLink, we estimated that payers incur an additional $26,178 in non-facility (professional and other ancillary) costs during the course of a meningococcal admission, as well as $22,230 in additional medical and pharmacy expenses for post-discharge care during the ensuing year. The majority of follow-up costs ($14,637) were attributed to repeat hospitalizations. Mean length of stay for meningococcal disease was consistently estimated across databases at 8 to 9 days. Data from the PCD further suggested that meningococcal disease carries, on average, nearly 2 days of intensive care unit utilization. In conclusion, hospital admissions for meningococcal disease are costly to payers. These costs are heightened when non-facility services and post-discharge care are also considered. Awareness of the full cost burden of meningococcal disease is needed when evaluating vaccination programs targeting the disease.

Open Access Article

Haemophilus influenzae vaccine candidate outer membrane protein P6 is not conserved in all strains

Arthur Chang, Ravinder Kaur, Lea Vacca Michel, Janet R. Casey and Michael Pichichero
Pages 102 - 105
http://dx.doi.org/10.4161/hv.7.1.13351
Abstract | PDF

An outer membrane protein of nontypeable Haemophilus influenzae (NTHi), P6, is a vaccine candidate because it has been characterized as conserved among all H. influenzae strains. Among 151 isolates from children, age 6 to 30 months, evaluating NTHi nasopharyngeal (NP) and oropharyngeal (OP) colonization and tympanocentesis confirmed acute otitis media we identified 14 strains (9.3%) that had variant protein sequences of P6. One atypical omp P6 isolate had sequence mutations in the binding site of a proposed major antigenic epitope of omp P6 identified by monoclonal antibody 7F3. Eight strains (5.3%) had non-homologous variations in amino acids that could result in significant changes to the protein structure of P6, and 5 other strains had amino acid substitutions at four previously described key residue sites. These results show that NTHi omp P6 is not invariant in its structure among respiratory isolates from children.




COMMENTARIES

Open Access Article

Lactococcus lactis-based vaccines: Current status and future perspectives

Mohammed Bahey-El-Din and Cormac GM Gahan
Pages 106 - 109
http://dx.doi.org/10.4161/hv.7.1.13631
Abstract | PDF

Lactococcus lactis offers significant potential as a platform for the delivery of vaccines especially via mucosal routes of administration. The organism has an established history of safe use in the food industry and is highly amenable to genetic manipulation, with many systems available for efficient production of secreted and surface-expressed proteins. Here we describe the benefits of using this organism as a vaccine delivery platform and outline how L. lactis based antigen delivery may be improved. Finally we discuss the safe use of L. lactis vectors and outline the potential for use of biological containment systems and killed lactococcal preparations.

Open Access Article

Sublingual vaccination

Cecil Czerkinsky, Nicolas Çuburu, Mi-Na Kweon, Fabienne Anjuere and Jan Holmgren
Pages 110 - 114
http://dx.doi.org/10.4161/hv.7.1.13739
Abstract | PDF

The sublingual route has been used for many years to deliver drugs and small molecules to the bloodstream. Surprisingly, the potential of this route for delivering vaccines has received very little if any attention until recently. During the past few years, a number of laboratories have documented the efficacy of sublingual immunization for inducing a broad range of immune responses in different experimental animal systems using a variety of antigens, including soluble proteins, inert particulate antigens (killed viruses, virus-like particles, bacterial extracts) as well as live-attenuated viruses. In most cases, systemic and mucosal immune responses, including humoral and cytotoxic T-cell responses were induced in both mucosal and extra-mucosal tissues. Overall, sublingual immunization was comparable to nasal immunization regarding the magnitude, breadth, and anatomic dissemination of the induced immune responses. Importantly, and contrary to nasal administration, sublingual administration did not redirect antigens and/or adjuvants to the brain. Here we review the results of pre-clinical studies using animal models of respiratory, intestinal and genital infections. These promising results provide a foundation for testing the approach in humans.

Open Access Article

The 2009 H1N1 influenza pandemic: A case study of how modeling can assist all stages of vaccine decision-making

Bruce Y. Lee and Ann E. Wiringa
Pages 115 - 119
http://dx.doi.org/10.4161/hv.7.1.13740
Abstract | PDF

During the 2009 H1N1 influenza pandemic nearly every decision associated with new vaccine development and dissemination occurred from the Spring of 2009, when the novel virus first emerged, to the Fall of 2009, when the new vaccines started reaching the thighs, arms and noses of vaccinees. In many ways, 2009 served as a crash course on how mathematical and computational modeling can assist all aspects of vaccine decision-making. Modeling influenced pandemic vaccine decision-making, but not to its fullest potential. The 2009 H1N1 pandemic demonstrated that modeling can help answer questions about new vaccine development, distribution, and administration such as (1) is a vaccine needed, (2) what characteristics should the vaccine have, (3) how should the vaccine be distributed, (4) who should receive the vaccine and in what order and (5) when should vaccination be discontinued? There is no need to wait for another pandemic to enhance the role of modeling, as new vaccine candidates for a variety of infectious diseases are emerging every year. Greater communication between decision makers and modelers can expand the use of modeling in vaccine decision-making to the benefit of all vaccine stakeholders and health around the globe.

Open Access Article

Non-specific and sex-differential effects of routine vaccines: What evidence is needed to take these effects into consideration in low-income countries?

Peter Aaby and Christine S. Benn
Pages 120 - 124
http://dx.doi.org/10.4161/hv.7.1.13848
Abstract | PDF

None of the original vaccines used in the child immunization programmes in low-income countries, including BCG, diphtheria-tetanus-pertussis (DTP), oral polio vaccine (OPV), and measles vaccine (MV), were tested for their overall effect on child mortality before being introduced. It was assumed that the effect on overall child mortality would be equivalent to the proportion of deaths caused by the targeted disease(s) (1). However, this is no longer a tenable assumption. Many studies have shown that these routine vaccines may have more general effects on the immune system than merely protecting against the targeted disease, i.e. so-called non-specific effects (NSE) (2). The NSE may well be more important for overall child survival than the lives saved by specific disease prevention (2-4). The WHO´s Global Advisory Committee on Vaccine Safety (GACVS) has recently stated that it will keep a watch on the non-specific effects (NSE) of vaccination. GACVS indicated that “conclusive evidence for or against non-specific effects of vaccines on mortality, including a potential deleterious effect of DTP vaccination on children’s survival as has been reported in some studies, was unlikely to be obtained from observational studies” (5). By insisting on new RCTs to provide conclusive evidence, GACVS is making it very difficult if not impossible to test the NSEs of the currently recommended vaccines. It would usually be considered unethical to test currently recommended vaccines as part of a trial withholding these vaccines from some children (6).

Open Access Article

Design-around biotechnology patents: An analysis of US Federal Circuit decisions shows the possibility of designing around biotechnology patents

Shyh-Jen Wang
Pages 125 - 128
http://dx.doi.org/10.4161/hv.7.1.13943
Abstract | PDF

In order to demonstrate the possibility of design-around for patents, we reviewed 40 no-infringement cases out of all 4,760 Federal Circuit Court of Appeals (CAFC) cases decided from 2001 to 2009. Based on this analysis, designing around a biotechnology patent first requires a thorough reading of the patent specification and prosecution history. These written descriptions offer explicit directions about claim meanings or the scope being disclaimed. By statute, claims recite and define the structure or acts of an invention, and serve as tools to determine whether or not a patent is infringed. The next procedure would include omitting a part or property from the claim, reversing the action used in the claim, or changing the claim’s structure or range to prevent the new design from falling within the scope of the claim. However, cases where patent infringement was found demonstrated that changing the structure or range not recited in the claim, such as enlarging the diameter, reducing concentration or alerting the shape, still falls within the scope of the patent. Although the 40 cases analyzed in this study were not related to vaccines, the thought process can serve as a guideline for patents related to vaccine development.




LETTERS

Open Access Article

Comment on “Forecasting dengue vaccine demand in disease endemic and non-endemic countries” Amarasinghe et al; Human Vaccines 2010; 6:9, 745-753.

Nicholas Miller
Pages 129 - 130
http://dx.doi.org/10.4161/hv.7.1.14142
Abstract | PDF

Recent forecasts of dengue travel vaccine demand, while worthy, might be improved by modelling future travel flows, and by accounting for incremental reductions in demand at the different points in the sequence of events leading to travel vaccine purchase. In particular, we suggest that an alternative method of projecting dengue travel vaccine uptake would account for (1) future flows of travellers from all non-endemic source to all endemic destination countries, based on data that are comparable between countries, and corrected for double-counting and other sources of error; (2) the proportion of such travellers that seek premedical travel advice within a timescale compatible with the probable dengue vaccine schedule; (3) the proportion of these travellers that will present with a combination of risk factors (above and beyond destination country) sufficient to prompt a physician to prescribe a dengue vaccine; and (4) the proportion of these travellers that actually purchase a vaccine when advised to do so.

Open Access Article

Reply letter

Ananda Amarasinghe, Ole Wichmann, Harold S. Margolis and Richard T. Mahoney
Page 131
http://dx.doi.org/10.4161/hv.7.1.14267
Abstract | PDF

We acknowledge the comments by N. Miller¹ on our estimates of the potential dengue vaccine demand among international travelers.² We agree that the number of travelers in 2015-20 would be the appropriate baseline from which to generate vaccine demand for this group and would be comparable to what we used for dengue endemic countries. While projections for this time horizon are much more reliable for country populations, they are much more difficult to estimate for international traveler arrivals since these events are substantially influenced by global financial and local political developments.