Table of Contents

Volume 2, Issue 5

  September/October 2006

  Pages 195 - 229

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 Issue Catalogue (MARC XML)

RESEARCH PAPERS

Open Access Article

A Fluorescent Peptide Substrate for Measuring the ADP-Ribosylation Activity of the Cholera Toxin A-Subunit

Chun-Ting Yuen and Sjoerd Rijpkema
Pages 195 - 199
http://dx.doi.org/10.4161/hv.2.5.3105
Abstract | PDF

Vibrio cholerae serogroups O1 and O139 Bengal produce cholera toxin (CT) a typical AB5 bacterial toxin comprising an ADP-ribosylation enzyme A-subunit (CTA) and a carbohydrate binding B-subunit (CTB). DUKORALR the inactivated oral cholera vaccine has recently been licensed for use in the European Union. This vaccine contains killed whole cells of V. cholerae and 1 mg of purified recombinant CTB (rCTB). DUKORAL^R has a good safety profile and there has been no indication that active CT is present. Nevertheless, an assay that confirms the absence of active CTA in the vaccine is advantageous to ensure vaccine safety. Conventional assays such as the Y-cell assay can not detect biologically active amounts of CT in DUKORAL^R because of the large amount of rCTB present. We have developed an assay based on a fluorescently labelled 11-mer peptide substrate that detects CTA activity despite the presence of excess rCTB.

Open Access Article

Comparison of Safety and Immunogenicity of Purified Chick Embryo Cell Rabies Vaccine (PCECV) and Purified Vero Cell Rabies Vaccine (PVRV) Using the Thai Red Cross Intradermal Regimen at a Dose of 0.1 ML

Shampur N. Madhusudana, Thitamaranahalli V. Sanjay, Bangalore J. Mahendra, M.K. Sudarshan, Doddabele H. Ashwath Narayana, Anand Giri, Kader Muhamuda, Vasanthapuram Ravi, Hoshang B. Vakil and Cladius Malerczyk
Pages 200 - 204
http://dx.doi.org/10.4161/hv.2.5.3197
Abstract | PDF

Intradermal (ID) vaccination with modern cell culture rabies vaccines is a means to significantly reduce the cost of post-exposure prophylaxis as compared to intramuscular vaccination. In this study we evaluated the efficacy, immunogenicity and tolerability of PCECV and PVRV administered ID in doses of 0.1 mL per site according to the 2-site Thai Red Cross (TRC) regimen. Patients with WHO category III exposure to suspect or laboratory proven rabid animals were administered either PCECV (n=58) or PVRV (n=52) ID at a dose of 0.1 mL per site on days 0, 3 and 7 and at one site on days 30 and 90. Serum samples were withdrawn on days 0, 14, 30, 90, and 180 and rabies virus neutralizing antibody (RVNA) titers were determined by rapid fluorescent focus inhibition test (RFFIT). Patients who were exposed to laboratory confirmed rabid animals were followed up for one year after exposure. All 110 patients developed RVNA titers above 0.5 IU/mL by day 14. Adequate titers >0.5 IU/mL were maintained up to day 180. Both vaccines induced equivalent RVNA titers at all time points and were well tolerated. Five subjects who were bitten by laboratory confirmed rabid dogs were alive and healthy one year after exposure. As demonstrated, PCECV and PVRV are both immunogenic, efficacious and well tolerated when administered in the TRC post-exposure prophylaxis regimen in ID doses of 0.1 mL as recommended by WHO guidelines. The use of PCECV in this regimen may prove more economical in developing countries like India.

Open Access Article

Safety and Immunogenicity of a Combination: Measles, Mumps, Rubella and Varicella Vaccine (ProQuad®)

Barbara J. Kuter, Michelle L. Hoffman Brown, Jonathan Hartzel, Wendy R. Williams, Karen A. Eves, Steve Black, Henry Shinefield, Keith S. Reisinger, Colin D. Marchant, Bradley J. Sullivan, Marci Thear, Stephanie Klopfer, Jin Xu, Jacqueline O. Gress, Florian Schödel and Study Group for ProQuad®
Pages 205 - 214
http://dx.doi.org/10.4161/hv.2.5.3246
Abstract | PDF

Background: A combination measles, mumps, rubella, and varicella vaccine (ProQuad®, Merck & Co., Inc, West Point, PA) was evaluated in 5 clinical trials. Use of ProQuad® would result in fewer injections for children and would facilitate universal immunization against all 4 diseases. Objective: To describe the combined results obtained from the studies conducted during the clinical development program for ProQuad®. Methods: A total of 5833 healthy children, 12-23 months of age, and 399 healthy children, 4-6 years of age, received 1 or 2 doses of ProQuad® in 5 controlled clinical trials. M-M-R®II and VARIVAX® were used as the control for most studies. Safety was evaluated for 6 weeks postvaccination and immunogenicity was assessed 6 weeks after each dose by a sensitive assay (ELISA or gpELISA). Results: A single dose of ProQuad® in 12- to 23-month-old children was shown to be as immunogenic as a single dose of M-M-R®II and VARIVAX® and was generally well tolerated. ProQuad® can be used concomitantly with other vaccines (hepatitis B and Haemophilus influenzae b). A higher rate of fever was reported after 1 dose of ProQuad® compared to M-M-R®II and VARIVAX®, but fever episodes were transient without long-term sequelae. Both a 2-dose regimen of ProQuad® in 12- to 23-month-olds and use of ProQuad® in place of M-M-R®II at 4-6 years were shown to be immunogenic and well tolerated. The incidence of adverse experiences following a second dose of ProQuad® was lower than that following the initial dose. Conclusions: A single dose of ProQuad® is as immunogenic as M-M-R®II and VARIVAX® and is well tolerated in a 1- or 2-dose schedule. ProQuad® should easily fit into the routine immunization schedule.

Open Access Article

Fever as a Marker of Reactogenicity of an Acellular Pertussis-Containing Hexavalent Vaccine (HEXAVAC®) in a Large-Scale, Open, Randomized Safety Study in Healthy French Infants

Philippe Reinert, Michael Watson, Anne Fiquet, Stéphane Thomas and Anne Schuyleman
Pages 215 - 221
http://dx.doi.org/10.4161/hv.2.5.3220
Abstract | PDF

Objective: New multivalent vaccines simplify childhood immunisation schedules and can increase vaccination coverage. However, they must have a reactogenicity profile which is acceptable and comparable with that of previously available vaccines. The objective of this trial was to assess the incidence of fever of 40.0°C or higher following vaccination with HEXAVAC® or concomitant PENTACOQ® and HBVAXPRO™.
Study design: This was an open, randomised, pragmatic, post-licensure multicentre trial performed in France. Infants were randomly assigned to receive either a single injection of a hexavalent, aP-containing vaccine (HEXAVAC®) or separate injections of a pentavalent, wP-containing vaccine (PENTACOQ®) and Hepatitis B vaccine (HBVAXPRO™) at 2, 3 and 4 months of age. Both groups received a HEXAVAC® booster at 12-18 months of age.
Results and discussion: 7151 infants were enrolled in 389 centres. During the combined 3-day periods following the primary series injections, the incidence of fever of 40.0°C or higher with HEXAVAC® was not greater than with [PENTACOQ® and HBVAXPRO™]. The incidence of fever at thresholds of 38.0°C, 38.5°C, 39.0°C and 39.5°C was significantly lower in the HEXAVAC group. The vaccine attributable risk for fever of 40.0°C following the booster injection with HEXAVAC® was statistically acceptable.
Conclusion: The incidence of fever of 40.0°C higher in this study was very low and similar in both groups (HEXAVAC® or [PENTACOQ® + HBVAXPRO™] as a 3-dose primary series). Fever ≥ 38.0°C and ≤ 39.5°C was significantly less frequent following administration of HEXAVAC®. The incidence of fever of 40.0°C or higher following a HEXAVAC® booster dose was low in all infants studied.





SHORT REPORT

Open Access Article

Preclinical Evaluation of a Chimeric Malaria Vaccine Candidate in Montanide ISA 720®: Immunogenecity and Safety in Rhesus Macaques

Jan A.M. Langermans, Meike Hensman, Marcel van Gijlswijk, Dongmei Zhang, Weiqing Pan, Birgitte K. Giersing, Emily Locke, F. Dubovsky, Janet Wittes and A.W. Thomas
Pages 222 - 226
http://dx.doi.org/10.4161/hv.2.5.3276
Abstract | PDF

Several malarial antigens are in development as potential vaccine candidates as part of a concerted effort to control the disease, which kills more than one million people per year. Although some antigens have demonstrated an impact against the malaria parasite, Plasmodium falciparum, many researchers hypothesize that a combination of antigens will be required to generate high levels of efficacy against clinical disease. PfCP2.9 is a chimeric protein that includes MSP119 and domain III of AMA1 [AMA1 (III)] of Plasmodium falciparum in a single recombinant molecule. The antigen, formulated in Seppic’s ISA 720 adjuvant, is approaching Phase I clinical testing in humans.




COMMENTARY

Open Access Article

Delivering Papillomavirus Vaccines When and Where They’re Most Needed

Ian H. Frazer
Pages 227 - 229
http://dx.doi.org/10.4161/hv.2.5.3345
Abstract | PDF