Tick-Borne Encephalitis (TBE) Vaccination in Children: Advantage of the Rapid Immunization Schedule (i.e., days 0, 7, 21)
Tick-borne encephalitis (TBE) is an important, vaccine-preventable arthropod-borne disease, causing severe illness in children too. In order to evaluate the immune response to different licensed primary immunization schedules, a total of 294 children aged 1 to 11 years of age were enrolled in a randomized, controlled, multi-center trial. The subjects were vaccinated with the pediatric formulation of a TBE vaccine (Encepur children) according to the conventional schedule (Group C; N=73, vaccination on days 0, 28 and 300), the modified conventional schedule (Group M; N=139, vaccination on days 0, 21 and 300), or the rapid schedule (Group R; N=82, vaccination on Days 0, 7 and 21). Antibody titers as measured by neutralization-test (NT) and ELISA were determined on Days 0, 42, 180, 300, and 321. The demographic data of the study groups were similar. Most subjects (97%-100%) reached an NT titer of at least 1:10 on Day 42. On Day 42, the highest NT geometric mean titers (GMTs) were reached in Group C. In Group C and Group M, titers declined up to Day 300. Until Day 300, the highest NT-GMTs were maintained in Group R, notably without a decline compared to Day 42. Group M reached titers similar to Group R on Day 42, but these titers declined by 50% up to Day 180. Similar to the NT, on Day 42 highest geometric mean concentrations (GMCs) as measured by ELISA across all groups were reached in Group C. In all groups, titers declined until Day 300. On Day 300, GMC ELISA of Group R was higher compared to Group C and Group M. To conclude, the rapid immunization schedule in children not only provides fast protection but also leads to stable titers as measured by NT for at least 300 days after vaccination.
Reduced Production of RNA Transcripts from Individual DNA Plasmids Given in a Multivalent DNA Vaccine Formula
We conducted transient transfection studies using two DNA vaccines constructs encoding
two Plasmodium falciparum surface proteins, PfCSP and PfSSP2, and UM449 melanoma cells to
determine transcription and translation efficiencies. Plasmids were transfected individually or in
combination with an empty control plasmid with and without a functional CMV IE promoter.
Western blot analysis using NSF1, a monoclonal antibody specific for PfCSP, and UM449 cell
lysate revealed an abrogation in expression of PfCSP when a plasmid carrying the Pfcsp gene
was co-transfected with an empty control plasmid with a functional CMV IE promoter. When a
control plasmid without a functional CMV IE promoter was substituted in the expression study,
normal levels of PfCSP were detected by Western blot. Total RNA was isolated following
transfection and reverse transcriptase quantitative (RTQ)-PCR was performed. Levels of Pfcsp
and Pfssp2 transcripts decreased significantly when co-transfected with a control plasmid
containing a functional CMV IE promoter while transcript levels of Pfcsp and Pfssp2 were
significantly higher in cells co-transfected with a control plasmid without a functional CMV IE
promoter. The presence of multiple copies of a functional CMV IE promoter leads to a decrease
in expression of malaria antigens present in a multivalent vaccine mixture when transfected in
A Clinical Study to Assess the Safety and Immunogenicity of Attenuated Measles Vaccine Administered Intranasally to Healthy Adults
Background: Despite the availability of a safe and effective vaccine for over four decades, measles remains one of the most common infectious disease killers of children in the world. Mucosal administration of currently licensed measles vaccine has been proposed to address issues of needle safety and improve vaccine uptake.
Methods: Healthy adult volunteers were randomized to receive live-attenuated monovalent measles virus vaccine (Moraten Berna) via the standard subcutaneous (SQ) or the experimental intranasal (IN) route in a randomized, double-masked fashion. Safety, reactogenicity, immunogenicity, and shedding were assessed.
Results: Safety, reactogenicity, and viral shedding were not significantly different in the two study groups. Immunogenicity was markedly lower in the group of volunteers that received vaccine via the IN route. Plaque reduction neutralization (PRN) geometric mean titers (GMT) were 125 (95% confidence interval [CI] 68-228) milli International Units per milliliter (mIU/mL) on day 28 in recipients of IN vaccine versus 645 (95% CI 468-889) mIU/mL in recipients of vaccine SQ; p<0.001 by Mann-Whitney Rank Sum. 50 % of measles non-immune individuals mounted titers above the protective threshold of PRN 200 mIU/mL after IN administration versus 100% of volunteers who received the vaccine SQ.
Conclusion: Intranasal administration of live-attenuated measles vaccine was safe and well tolerated, but failed to mount significant immune responses when compared to subcutaneous administration. It is possible that higher doses or smaller particle size are necessary for successful intranasal measles vaccination and boosting.
Post-Licensure Safety of the Meningococcal Group C Conjugate Vaccine
Passive surveillance reports of adverse events following meningococcal group C conjugate vaccine (MCCV) in the United Kingdom suggested a possible increased risk convulsions and purpura. To investigate this further, hospital admissions for convulsions and purpura were obtained for the period November 1999 to September 2003 in children from the South East of England and these were linked to vaccine records for MCCV, Diphtheria/Tetanus/Pertussis vaccine (DTP) and Measles/Mumps/Rubella vaccine (MMR). A total of 1,715 children with convulsions and 363 with purpura were successfully linked to vaccination records. The self-controlled case-series method was then used to investigate whether there was any epidemiological evidence of an increased risk of convulsions or purpura following vaccination. The results showed that there was no evidence of an increased relative incidence (RI) of convulsions in the two weeks following MCCV with RI estimates (95% confidence intervals) of 0.57 (0.36-0.86), 1.03 (0.62-1.69) and 0.81 (0.51-1.30) for children aged <1, 1, 2-17 years respectively. There was also no increased relative incidence of purpura in the 4 weeks following MCCV, with an overall RI of 1.15 (0.80-1.67). There was evidence of an increased risk of convulsions and idiopathic thrombocytopenic purpura following MMR vaccination as previously documented.