Table of Contents

Volume 3, Issue 1

  January/February 2007

  Pages 1 - 36

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 Issue Catalogue (MARC XML)

REVIEW

Open Access Article

Biological Feasibility of Developing Prophylactic Vaccines for Viral Pathogens: Incubation Period as a Critical Parameter

David C. Kaslow
Pages 1 - 7
http://dx.doi.org/10.4161/hv.3.1.3519
Abstract | PDF

Vaccines for sixteen major human viral pathogens have been approved for use in humans. For most other major human viral pathogens, the absence of an efficacious prophylactic vaccine is not for lack of effort. To identify the key parameters of biologic feasibility that determine “certainty-of-success” for developing prophylactic vaccines for major human viral pathogens, basic characteristics of viruses, such as primary genomic structure, route of transmission, and durability of viral infection were reviewed. These basic characteristics of viruses simply do not associate with successful vaccine development, so one must look elsewhere for characteristics predictive of successful vaccine development. Herein existing data are put forth in a way that demonstrates the impact of the combined effect of incubation period and broadly protective, relative immunogenicity on the “certainty-of-success” of developing effective vaccines for thirty viral pathogens. Both incubation period and broadly protective, relative immunogenicity appear to have accounted for much of the past successes in vaccine development, and may be useful in predicting where near term successes are most apt to occur.




RESEARCH PAPERS

Open Access Article

Therapeutic Vaccination with Epidermal Growth Factor (EGF) in Advanced Lung Cancer: Analysis of Pooled Data from Three Clinical Trials

Gisela González, Tania Crombet, Elia Neninger, Carmen Viada and Agustín Lage
Pages 8 - 13
http://dx.doi.org/10.4161/hv.3.1.3537
Abstract | PDF

We have undertaken the analysis of pooled data from three pilot clinical trials of vaccination with Epidermal Growth Factor (EGF) in patients with advanced non small cell lung cancer (NSCLC), addressing particularly the issue of the relationship between immunization and survival. Eighty-three patients with advanced disease were included in 3 pilot clinical trials and vaccinated with the EGF Vaccine. The trials were designed to evaluate the immunogenicity and safety of the vaccine using different adjuvants, cyclophosphamide pre-treatment or not, and different dosage levels of the vaccine. The vaccine elicited specific anti-EGF antibody titers in 83% of subjects, and 49% developed a good anti-EGF antibody response. The adjuvant, the vaccine dose, and cyclophosphamide pre-treatment significantly influenced immunogenicity. Patients that seroconverted survived significantly longer than patients who did not. Good antibody responders survived significantly longer than poor responders. Pooled results from these trials confirm that vaccination with EGF is safe and immunogenic in advanced NSCLC patients. The association between good antibody responses and survival consistently appeared in every single trial independently of the specific trial designs. Although these were small pilot non-randomized clinical trials not intended to confirm therapeutic effect, the survival of the pooled patient population was statistically greater compared with 163 control patients receiving standard treatment.

Open Access Article

Cost-Effectiveness of Adjuvanted Influenza Vaccination of Healthy Children 6 to 60 Months of Age

Monia Marchetti, Ursula M. Kuehnel, Giorgio L. Colombo, Susanna Esposito and Nicola Principi
Pages 14 - 22
http://dx.doi.org/10.4161/hv.3.1.3657
Abstract | PDF

This study estimated the health and economic outcomes of universal administration of a adjuvanted influenza vaccine to healthy pre-school children, as compared with current immunisation practice. A Markov model simulated a cohort of 3 million children and their households undergoing 5 influenza seasons. Assuming a vaccine uptake rate of 30%, at the current acquisition cost of €5.50 per vaccine dose influenza vaccination (two doses for unprimed children) of 6- to 60-month- (5-year) old children averted more than 1 million clinical influenza episodes and saved €63 million, from the perspective of the Italian society. From the perspective of the Italian health care service, influenza vaccination of 6- to 60- and of 6- to 24-month-old children cost €10,000 and €13,333 per quality-adjusted life year (QALY) saved, respectively. Administration of a adjuvanted influenza vaccine to children aged 6 to 60 months was highly cost-effective for the health care service and cost saving for the society.

Open Access Article

Estimating the Number of Deaths with Rotavirus as a Cause in England and Wales

Mark Jit, Richard Pebody, Mark chen, Nick Andrews and John Edmunds
Pages 23 - 26
http://dx.doi.org/10.4161/hv.3.1.3748
Abstract | PDF

The precise number of deaths due to rotavirus infection in England and Wales is difficult to determine because mortality is usually low and reported simply as death due to gastrointestinal disease. We have used two independent methods to estimate this figure. Firstly, we obtained records from the Office for National Statistics of deaths in children with any mention of gastroenteritis. For deaths with uncertain aetiology, we estimated the proportion attributable to rotavirus using a linear model with monthly laboratory reports of gastrointestinal micro-organisms as predictors. Secondly, we calculated the case-fatality ratio of records in Hospital Episode Statistics with rotavirus indicated, and applied this ratio to an estimate of the actual number of rotavirus hospital admissions. The two methods gave estimates of 3.8 and 3.2 rotavirus deaths a year respectively.

Open Access Article

Long-Term Thermal Stability of Group C Meningococcal Polysaccharide-Tetanus Toxoid Conjugate Vaccine

Shwu-Maan Lee, Robert Petermann, Quallyna Porte, Greg Berezuk, Brian Crowe and John Shirtz
Pages 27 - 32
http://dx.doi.org/10.4161/hv.3.1.3749
Abstract | PDF

The stability of vaccines during storage and handling is a prerequisite for optimal potency at the time of immunization. Meningococcal group C conjugate vaccines have been successfully incorporated in mass immunization programs, however, thus far no long-term real-time stability studies of these vaccines have been reported. Stability of de-O-acetylated group C meningococcal polysaccharide coupled to tetanus toxoid (GCMP-TT) was evaluated in real time on the basis of immunogenicity and physiochemical properties. The vaccine is formulated as a 0.5 mL suspension containing 10 microgram GCMP conjugated to 10-20 microgram of TT adsorbed on 0.5 mg aluminum in saline. The single dose syringes were stored under refrigeration (5 ± 3 {degree sign}C) and at room temperature (25 ± 2 {degree sign}C) for up to 42 months and at elevated temperature (40 ± 2 {degree sign}C) for up to 6 months. At both refrigerated and room temperatures, no time-dependent change in animal potency was detectable through 42 months. After the 9 months maximum recommended storage period at room temperature, 96% of the baseline serum bactericidal antibody (SBA) titer was maintained. Time-dependent decreases in SBA level and anti-GCMP-TT IgG level were observed at 40 ± 2 {degree sign}C. No changes in GCMP-TT adsorption and pH occurred in all the studies. Loss of integrity increased over 6 months at 40 ± 2 {degree sign}C (p = 0.004). Free sugar content did not change over 36 months under refrigeration. GCMP-TT retained immunogenicity and physicochemical properties under refrigeration and at room temperature (25 ± 2 {degree sign}C) for up to 42 months.

Open Access Article

Influenza Vaccination Coverage and Predictors for Vaccination Among Spanish Healthcare Workers

Rodrigo Jiménez-García , Pilar Carrasco-Garrido, Valentin Hernandez-Barrera and Angel Gil de Miguel
Pages 33 - 36
http://dx.doi.org/10.4161/hv.3.1.3750
Abstract | PDF

This study aimed to examine influenza vaccination status and predictors for vaccine receipt among Spanish healthcare workers. A descriptive cross-sectional study was conducted using individualized data provided by the 2001 and 2003 National Health Surveys. Adults were classified as HCWs if they were employed in a healthcare occupation or in a healthcare industry setting. Influenza coverage was significantly higher among HCWs versus non-HCWs (18.2% vs. 10.9%), after adjusting for potential confounders, the likelihood of being vaccinated remained higher among HCWs (OR =2.38 CI 95% 1.91-2.96). Older age and suffering a high risk medical condition were independent predictors for vaccination among HCWs. We conclude that influenza vaccination coverages among Spanish HCWs are much underneath the desirable level. Efforts should be tailored to individuals, institutions, and healthcare systems to dramatically increase HCWs immunization rates in Spain.