Table of Contents

Volume 6, Issue 3

  March 2010

  Pages 225 - 282

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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 225
http://dx.doi.org/10.4161/hv.6.3.11604
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LETTER

Open Access Article

Apropos: A heat-stable hepatitis B vaccine formulation

Subhash C. Arya and Nirmala Agarwal
Page 226
http://dx.doi.org/10.4161/hv.6.3.11022
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NEWS & POLICY

Open Access Article

Immunotherapeutic vaccine extends life of prostate cancer patients

Eva M. Riedmann
Pages 227 - 231
http://dx.doi.org/10.4161/hv.6.3.11613
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Open Access Article

Prevenar 13 authorized in Europe

Eva Riedmann
Pages 227 - 231
http://dx.doi.org/10.4161/hv.6.3.11614
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Open Access Article

Rotavirus vaccine could save millions of children worldwide

Eva Riedmann
Pages 227 - 231
http://dx.doi.org/10.4161/hv.6.3.11615
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Open Access Article

New Malaria vaccine proves promising in Mali children

Eva Riedmann
Pages 227 - 231
http://dx.doi.org/10.4161/hv.6.3.11616
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Open Access Article

Travelers’ Diarrhea patch: efficacy trial in India

Eva Riedmann
Pages 227 - 231
http://dx.doi.org/10.4161/hv.6.3.11617
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Open Access Article

Stabilization of vaccines: Lessons learned

Debra Kristensen and Dexiang Chen
Pages 227 - 231
http://dx.doi.org/10.4161/hv.6.3.11618
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PORTRAIT OF A LEADING VACCINOLOGIST

Open Access Article

How pediatricians can contribute to the development of vaccines

Nicola Principi
Pages 232 - 234
http://dx.doi.org/10.4161/hv.6.3.11605
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BOOK REVIEW

Open Access Article

Immunity against mucosal pathogens

Jennelle Kyd
Pages 235 - 236
http://dx.doi.org/10.4161/hv.6.3.10016
Abstract | PDF

Immunity against mucosal pathogens-Editor: Michael Vajdy

This book highlights the importance of the close interactions of the mucosal immune system with the systemic immune system and the breadth of pathogens and the diversity of pathogenesis associated with infections at mucosal surfaces. The pathogens detailed in the book epitomize the challenges that confront mucosal immunologists and infectious disease researchers. The reader will gain significant insights into these challenges and approaches that researchers attempting to understand mucosal immunology and host-bacterial interactions take to develop effective therapeutic and prophylactic approaches to infection.




REVIEW

Open Access Article

ISCOMATRIX™ vaccines: Safety in human clinical studies

Andrew McKenzie, Marli Watt and Charmaine Gittleson
Pages 237 - 246
http://dx.doi.org/10.4161/hv.6.3.10754
Abstract | PDF

ISCOMATRIX™ adjuvant is a component of a variety of developmental vaccines. To evaluate the safety profile of ISCOMATRIX™ adjuvant we have pooled and analyzed the safety data obtained from a number of vaccine development programs. Overall, the ISCOMATRIX™ vaccines from studies included in the analysis were found to be safe and well tolerated, with no vaccine related deaths or Serious Adverse Events. A greater proportion of subjects who received ISCOMATRIX™ vaccines experienced local and systemic reactogenicity compared with subjects who received placebo or active comparator, however this reactogenicity was generally mild, self-limiting and of short duration. Similar safety profiles were seen for each of these vaccines. To date, the ISCOMATRIX™ vaccines have not been associated with events suggestive of autoimmune or allergic disorders. Specifically, analysis of the ISCOMATRIX™ adjuvant adverse event database showed that there was no clustering of symptoms to suggest an allergic or autoimmune syndrome. Additionally, there were no reported autoimmune diagnoses and no events of anaphylaxis per se reported in any of the studies. Generally ISCOMATRIX™ adjuvant did not adversely affect safety laboratory parameters and there was no clinically significant difference observed between studies or treatment groups. Studies using ISCOMATRIX™ vaccines are ongoing and we continue to proactively analyze the safety of ISCOMATRIX™ adjuvant.




RESEARCH PAPERS

Open Access Article

Molecular characterization of human rotavirus vaccine strain CDC-9 during sequential passages in vero cells

Mathew D. Esona, Kimberly Foytich, Yuhuan Wang, Gary Shin, Gang Wei, Jon R. Gentsch, Roger I. Glass and Baoming Jiang
Pages 247 - 253
http://dx.doi.org/10.4161/hv.6.3.10409
Abstract | PDF

We have developed several candidate human rotavirus vaccine strains with common serotypes via adaptation in Vero cells, adhering to the Good Laboratory Practice (GLP) guidelines. We sequenced the entire genome of a G1P[8] strain CDC-9 in original stool and passaged materials from Vero cells and examined its genetic relatedness to the prototype human rotavirus KU and other strains. With the exception of VP3 gene which was closely related to that of strain DS-1, the culture-adapted CDC-9 strain shared moderate to high nt (range 83.4%-95.1%) and deduced aa (range 81.3%-97.9%) sequence identities with the KU and other G1P[8] strains. Alignments of the deduced aa sequences of 11 gene segments of the wild-type and culture-adapted CDC-9 showed complete sequence identity in genes encoding NSP2, NSP3, NSP4, VP1, VP2, VP3, and VP7, a single aa change in genes coding for NSP1, NSP5, and VP6 and several scattered aa changes in the VP4 gene during the passage in Vero cells. Two of the VP4 aa substitutions (385 and 388) are within sites associated with neutralization resistant mutants selected by cross-reactive monoclonal antibodies. Although some sequence changes were evident, we do not know if these changes contribute to the possible attenuation of this strain. Further testing of this vaccine strain in clinical trials is justified.

Open Access Article

Immunogenicity of a live-attenuated human rotavirus RIX4414 vaccine with or without buffering agent

Angkool Kerdpanich, Kulkanya Chokephaibulkit, Veerachai Watanaveeradej, Nirun Vanprapar, Sriluck Simasathien, Nopaorn Phavichitr, Hans L Bock, Silvia Damaso, Yanee Hutagalung and Htay-Htay Han
Pages 254 - 262
http://dx.doi.org/10.4161/hv.6.3.10428
Abstract | PDF

Aim: The lyophilized form of the human rotavirus RIX4414 vaccine (Rotarix™) is usually reconstituted with a liquid calcium carbonate (CaCO3) buffer and administered orally. However, errors in the reconstitution could occur (e.g. reconstituted with water instead of CaCO3 buffer) or the buffer might be temporarily unavailable in few instances. This study was conducted to evaluate the immunogenicity of the RIX4414 vaccine if the vaccine was reconstituted with other agents (e.g. water) instead of CaCO3 buffer. Methods: Healthy infants aged 6–12 weeks, received two oral doses of the RIX4414 vaccine/placebo, reconstituted either with injectable water or CaCO3 buffer according to a 0, 2 month schedule. Seroconversion rates in terms of anti-rotavirus Immunoglobulin A (anti-RV IgA) antibody levels (cut off: ≥ 20U/ml by ELISA) and vaccine take were calculated 2 months post-Dose 2. Solicited and unsolicited symptoms reported during the 15- and 31-day follow-up period after each dose and serious adverse events (SAEs) reported during the entire study period were recorded. Results: There was no statistical difference detected between RIX4414 vaccine reconstituted with buffer or water in vaccine take or in seroconversion rate. The anti-RV IgA seroconversion rate 2 months post-Dose 2 was 84.7% (95% CI: 78.1–90.0) for the group with buffer and 78.6% (95% CI: 71.2–84.8) for the group with water. Solicited and unsolicited symptoms reported were similar across groups. No vaccine related SAEs were reported. Conclusion: Administration of RIX4414 vaccine in the absence of CaCO3 buffer was shown to be well tolerated and immunogenic in Thai infants.

Open Access Article

Booster vaccination against pertussis in Chinese children at six years of age using reduced antigen content diphtheria-tetanus-acellular pertussis vaccine (Boostrix™)

Fengcai Zhu, Shumin Zhang, Qiming Hou, Yiju Zhang, Yinghua Xu, Xiao Ma, Xidong Lu, Hongxing Pan, Dengfeng Chen, Gunasekaran Ramakrishnan, Richard Zhao, Haiwen Tang, Olivier Van Der Meeren and Hans L Bock
Pages 263 - 269
http://dx.doi.org/10.4161/hv.6.3.10503
Abstract | PDF

Pertussis continues to circulate in Chinese communities and older children, adolescents and adults are sources of infection for unprotected infants. Two studies conducted in Jiangsu Province in the People’s Republic of China assessed the immunogenicity, reactogenicity and safety of Boostrix™, a combined reduced antigen content diphtheria-tetanus-acellular pertussis vaccine (dTpa) when administered as a booster dose to children 6−8 years of age. Immunogenicity was assessed before and one month after vaccination in a subset. Reactogenicity was assessed over a 4-day follow-up using diary cards. A total of 690 Chinese subjects were enrolled. Boostrix™ was well tolerated. One month after the booster dose, 100% of dTpa recipients had seroprotective antibody concentrations against diphtheria and tetanus. The percentage of subjects with a response against pertussis antigens (using locally defined cut-offs) was 91.9% for pertussis toxoid, 98.8% for filamentous hemagglutinin, and 100% for pertactin. The exploratory analysis showed no statistically significant differences between dTpa or diphtheria-tetanus vaccine in terms of the percentage of subjects with seroprotective antibodies against diphtheria or tetanus. These studies demonstrate that Boostrix™ is well tolerated and immunogenic when administered as a booster dose to 6−8 year old Chinese children previously immunized with a combined diphtheria-tetanus-pertussis vaccine. Introduction of dTpa into the routine Chinese immunization schedule would provide booster vaccination against pertussis without the addition of further injections into the Chinese vaccination schedule and is likely to promote improved pertussis control in older children.

Open Access Article

Impact of wastage on single and multi-dose vaccine vials: Implications for introducing pneumococcal vaccines in developing countries

Divya Parmar, Elaine M Baruwa, Patrick Zuber and Souleymane Kone
Pages 270 - 278
http://dx.doi.org/10.4161/hv.6.3.10397
Abstract | PDF

Introduction: Pneumococcal conjugate vaccines are expensive relative to those in the EPI systems of low-income countries. The current single-dose presentation costs more to store in the cold chain relative to multi-dose presentations but also has lower wastage rates. It is, therefore, important to determine the optimal balance of vial size and storage costs after adjusting for wastage. Objectives: To project the cost implications of wastage when vaccine wastage rates vary across vial sizes using country specific wastage data. Methods: For each potential vial size, we estimated cold chain costs and the cost of wasted vaccine doses using country level wastage data and projections of the price per dose of vaccine and cold chain storage. Results: Only 19 (26%) of 72 GAVI eligible countries had analyzable wastage data at WHO/HQ. The median wastage rates for single, 2- and 10-dose vials were 5%, 7% and 10% respectively. However wastage varied between 1%-10%, 1%-27% and 4%-44% for single, 2- and 10-dose vials respectively. The increased variance for multi-dose vial wastage implied wastage costs potentially greater than the savings realized from lower storage volumes. Conclusions: The optimal vial-size for PCV is dependent upon country specific wastage rates but few countries have these data. There may be a role for both single and multi-dose vials that is best determined by local management and storage capacities making local wastage data critical. Without effective wastage monitoring and control there is a risk that wastage costs will possibly exceed the savings from multi-dose vials’ lower storage costs.




COMMENTARIES

Open Access Article

High titer human immunoglobulin as a specific therapy against West Nile virus encephalitis

David Ben Nathan, Itzchak Samina and Nadav Orr
Pages 279 - 281
http://dx.doi.org/10.4161/hv.6.3.10298
Abstract | PDF

WN virus is a mosquito-borne disease found most commonly in Africa, west Asia, and the Middle East, where up to 40% of the human population possesses antibodies. It is an emerging disease in the United States, since 1999 and has spread all over the US and Canada. The virus is maintained in nature in a mosquito-bird-mosquito cycle (primarily Culex), with human horses and other animals serving as incidental hosts. WN infection in humans is usually asymptomatic or involves flu like illness but can develop to severe meningo-encephlitis, with symptoms including cognitive dysfunctions, muscle weakness, paralysis and even death. Elderly and depressed immunity factors are at greatest risk of developing severe neurological disease. Studies in animal models have enhanced significantly the understanding of the viral and host factors that determine the pathogenesis and outcome of WNV disease. Currently, vaccines are available for animal use but there is no effective anti-viral therapy or human vaccine for WNV infection. Passive administration of antibodies produced from selected donors has been showed promising results in animal models.

Open Access Article

The enemy is sometimes us

Stanley Plotkin
Page 282
http://dx.doi.org/10.4161/hv.6.3.11388
Abstract | PDF

Read original paper in Health Affairs 2005; 24:631-4.