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J Immunol 2002 Oct 1;169(7):3908-13
 

Critical components of a DNA fusion vaccine able to induce protective cytotoxic T cells against a single epitope of a tumor antigen.

Rice J, Buchan S, Stevenson FK

Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals Trust, Southampton, United Kingdom.

[Medline record in process]
 

DNA vaccines can activate immunity against tumor Ags expressed as MHC class I-associated peptides. However, priming of CD8(+) CTL against weak tumor Ags may require adjuvant molecules. We have used a pathogen-derived sequence from tetanus toxin (fragment C (FrC)) fused to tumor Ag sequences to promote Ab and CD4(+) T cell responses. For induction of CD8(+) T cell responses, the FrC sequence has been engineered to remove potentially competitive MHC class I-binding epitopes and to improve presentation of tumor epitopes. The colon carcinoma CT26 expresses an endogenous retroviral gene product, gp70, containing a known H2-L(d)-restricted epitope (AH1). A DNA vaccine encoding gp70 alone was a poor inducer of CTL, and performance was not significantly improved by fusion of full-length FrC. However, use of a minimized domain of FrC, with the AH1 sequence fused to the 3' position, led to rapid induction of high levels of CTL. IFN-gamma-producing epitope-specific CTL were detectable ex vivo and these killed CT26 targets in vitro. The single epitope vaccine was more effective than GM-CSF-transfected CT26 tumor cells in inducing an AH1-specific CTL response and equally effective in providing protection against tumor challenge. Levels of AH1-specific CTL in vivo were increased following injection of tumor cells, and CTL expanded in vitro were able to kill CT26 cells in tumor bearers. Pre-existing immunity to tetanus toxoid had no effect on the induction of AH1-specific CTL. These data demonstrate the power of epitope-specific CTL against tumor cells and illustrate a strategy for priming immunity via a dual component DNA vaccine.

PMID: 12244189, UI: 22229551

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J Immunol 2002 Oct 1;169(7):3837-46
 

DNA-encoded fetal liver tyrosine kinase 3 ligand and granulocyte macrophage-colony-stimulating factor increase dendritic cell recruitment to the inoculation site and enhance antigen-specific CD4(+) T cell responses induced by DNA vaccination of outbred animals.

Mwangi W, Brown WC, Lewin HA, Howard CJ, Hope JC, Baszler TV, Caplazi P, Abbott J, Palmer GH

Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA. waitham@vetmed.wsu.edu

[Medline record in process]
 

DNA-based immunization is a contemporary strategy for developing vaccines to prevent infectious diseases in animals and humans. Translating the efficacy of DNA immunization demonstrated in murine models to the animal species that represent the actual populations to be protected remains a significant challenge. We tested two hypotheses directed at enhancing DNA vaccine efficacy in outbred animals. The first hypothesis, that DNA-encoding fetal liver tyrosine kinase 3 ligand (Flt3L) and GM-CSF increases dendritic cell (DC) recruitment to the immunization site, was tested by intradermal inoculation of calves with plasmid DNA encoding Flt3L and GM-CSF followed by quantitation of CD1(+) DC. Peak DC recruitment was detected at 10-15 days postinoculation and was significantly greater (p < 0.05) in calves in the treatment group as compared with control calves inoculated identically, but without Flt3L and GM-CSF. The second hypothesis, that DNA encoding Flt3L and GM-CSF enhances immunity to a DNA vector-expressed Ag, was tested by analyzing the CD4(+) T lymphocyte response to Anaplasma marginale major surface protein 1a (MSP1a). Calves immunized with DNA-expressing MSP1a developed strong CD4(+) T cell responses against A. marginale, MSP1a, and specific MHC class II DR-restricted MSP1a epitopes. Administration of DNA-encoding Flt3L and GM-CSF before MSP1a DNA vaccination significantly increased the population of Ag-specific effector/memory cells in PBMC and significantly enhanced MSP1a-specific CD4(+) T cell proliferation and IFN-gamma secretion as compared with MHC class II DR-matched calves vaccinated identically but without Flt3L and GM-CSF. These results support use of these growth factors in DNA vaccination and specifically indicate their applicability for vaccine testing in outbred animals.

PMID: 12244180, UI: 22229542

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J Immunol 2002 Sep 1;169(5):2545-52
 

Role of IL-12-independent and IL-12-dependent pathways in regulating generation of the IFN-gamma component of T cell responses to Salmonella typhimurium.

John B, Rajagopal D, Pashine A, Rath S, George A, Bal V

National Institute of Immunology, New Delhi, India.

Clearance of facultative intracellular pathogens such as Salmonella requires IFN-gamma from CD4 T cells. Mechanisms linking intracellular pathogen recognition with induction of IFN-gamma-producing T cells are still poorly understood. We show in this study that IL-12 is not required for commitment to the IFN-gamma-producing T cell response in infection with Salmonella typhimurium, but is needed for its maintenance. The IL-12-independent signals required for commitment depend on events during the first hour of infection and are related to Ag presentation. Even transient attenuation of Ag presentation early during infection specifically abrogates the IFN-gamma component of the resulting CD4 T cell response. The IL-12 needed for maintenance is also better induced by live rather than dead bacteria in vivo, and this difference is due to specific suppression of IL-12 induction by dead bacteria. Presence of exogenous IL-4 down-modulates IL-12 production by macrophages activated in vitro. Furthermore, macrophages from IL-4-null mice secrete high levels of both IL-12 and IL-18 in response to stimulation in vivo even with dead bacteria, but this does not lead to induction of IFN-gamma-secreting T cells in response to immunization with dead S. typhimurium. Early IL-4 is contributed by triggering of CD4 NK T cells by dead, but not live, bacteria. Thus, Ag presentation-related IL-12-independent events and IL-4-sensitive IL-12-dependent events play crucial complementary roles in the generation of the IFN-gamma-committed CD4 T cell component of the immune response in Salmonella infection.

PMID: 12193724, UI: 22181520

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JAMA 2002 Sep 18;288(11):1337-8
 

Sewage yields clues to SV40 transmission.

Vastag B

Publication Types:
 

• News

PMID: 12234213, UI: 22220564

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Pediatr Infect Dis J 2002 Sep;21(9):854-859
 

Impact of a birth dose of hepatitis B vaccine on the reactogenicity and immunogenicity of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b combination vaccination.

Pichichero ME, Blatter MM, Reisinger KS, Harrison CJ, Johnson CE, Steinhoff MC, Senders SD, Rothstein EP, Willems P, Howe BJ

[Record supplied by publisher]
 

OBJECTIVES To assess the impact of a birth dose of hepatitis B vaccine (HepB) on the reactogenicity and immunogenicity of a novel diphtheria-tetanus-acellular pertussis (DTaP)- HepB-inactivated poliovirus (IPV)/ type b (Hib) combination vaccine administered subsequently at 2, 4 and 6 months of age.METHODS Neonates ( = 550) were randomized into two groups with regard to receipt of HepB at birth. All subjects in both groups received DTaP-HepB-IPV/Hib at 2, 4 and 6 months of age. Solicited local and general adverse events were recorded for 8 days after each dose. Antibodies to hepatitis B surface antigen were measured 1 month after the third dose of DTaP-HepB-IPV/Hib in a subset of 170 infants; titers of at least 10 mIU/ml were considered protective.RESULTS The DTaP-HepB-IPV/Hib combination vaccine was well-tolerated in both groups. Of the infants who received a birth dose of HepB, 22.6% had severe (Grade 3) reactions after any of the three doses of DTaP-HepB-IPV/Hib combination vaccine compared with 23.2% of subjects who did not receive a birth dose of HepB (difference, -0.5%; 90% confidence interval, -7.4 to 6.1). Antibody to hepatitis B surface antigen titers were >/=10 mIU/ml for all tested infants. Geometric mean titers were 2996.2 and 1240.1 mIU/ml with and without a birth dose of HepB, respectively.CONCLUSIONS A HepB birth dose does not increase the reactogenicity of a combination DTaP-HepB-IPV/Hib vaccine administered at 2, 4 and 6 months of age, and all tested subjects achieved protective anti-HBs titers (>/=10 mIU/ml), although geometric mean titers were higher when a birth dose of HepB was given.

PMID: 12352809

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Pediatr Infect Dis J 2002 Sep;21(9):826-830
 

Consequences of delayed measles vaccination in Germany.

Siedler A, Hermann M, Schmitt HJ, Von Kries R

[Record supplied by publisher]
 

BACKGROUND In recent surveillance data there are still many cases of measles and even local epidemics in Germany. We studied whether delayed measles vaccination contributes to this situation.METHODS Vaccine coverage data in children <3 years of age were assessed by a telephone survey. Three data sources for measles surveillance were analyzed: official measles notifications; sentinel data; and official hospital discharge diagnoses.RESULTS After the time recommended for completion of measles vaccination at Month 15, only 22% of German children had received their first vaccine dose. This percentage increased to 77% at the age of 24 months and to 87% at 36 months of age. According to all three surveillance instruments, the number of measles cases was highest in children age 1 to 4 years with a peak in the second year of life.CONCLUSIONS More than 50% of measles cases in 1-year-old children would be prevented if presently observed vaccine coverage rates in the third year of life could be achieved 12 months earlier. Delayed measles vaccination is responsible for a large number of measles cases still occurring in the German population, where measles has not yet been eliminated. If vaccination were delivered according to the recommended time schedule, the incidence of measles would be considerably reduced.

PMID: 12352803

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Pediatr Infect Dis J 2002 Sep;21(9):822-826
 

Standard and alternative regimens of Haemophilus influenzae type b conjugate vaccine (polyribosylribitol phosphate-tetanus toxoid conjugate vaccine) elicit comparable antibody avidities in infants.

Campbell JD, Lagos R, Levine MM, Losonsky GA

[Record supplied by publisher]
 

BACKGROUND Haemophilus influenzae type b conjugate vaccines are relatively expensive in the developing world. Previous study of the type b conjugate vaccine polyribosylribitol phosphate-tetanus toxoid conjugate vaccine showed that two dose and fractional three dose schedules elicit protective antibody concentrations equivalent to three full doses.METHODS Antibody avidity was measured in 73 of these vaccinees with a modified enzyme-linked immunosorbent assay using NH SCN as the chaotrope. Avidity index (AI) is the molarity causing a 50% reduction in OD.(4) (405)RESULTS The postprimary series AI was similar for all dosing regimens. Preboost AI was highest in those receiving three half-doses, although there was no statistical difference among groups. Rises in avidity from age 8 to 12 months were also similar among regimens. Our data support the equivalence of anti-polyribosylribitol phosphate IgG avidity in infants primed with these alternative regimens.CONCLUSIONS Given the known correlation of avidity with assays of bacterial killing and memory priming, these potentially more economical alternative schedules should be studied in the developing world.

PMID: 12352802

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Pediatr Infect Dis J 2002 Sep;21(9):810-816
 

Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than five years of age for prevention of pneumonia.

Black SB, Shinefield HR, Ling S, Hansen J, Fireman B, Spring D, Noyes J, Lewis E, Ray P, Lee J, Hackell J

[Record supplied by publisher]
 

OBJECTIVE To determine the effectiveness of the Wyeth heptavalent pneumococcal conjugate vaccine against clinical and radiograph-confirmed pneumonia in children.METHODS The heptavalent CRM pneumococcal conjugate vaccine (PCV) was given to infants at 2, 4, 6 and 12 to 15 months of age in a randomized, double blind trial. Children were randomized to receive either the CRM PCV (vaccine group) or the meningococcal type C CRM conjugate vaccine (control group). The primary outcome of this trial was invasive pneumococcal disease. In addition children with the clinical diagnosis of pneumonia in the study population were identified through review of automated inpatient, emergency and outpatient databases. The subset of the cohort of these children who had chest radiographs obtained at the time of diagnosis was identified, and the original reading of their radiographs by the radiologist was obtained from automated databases. Rates of clinically diagnosed pneumonia, of pneumonia with a radiograph obtained regardless of result, of pneumonia with positive radiograph (consolidation, empyema or parenchymal infiltrate) and of pneumonia with only perihilar infiltrates were compared between vaccinated and nonvaccinated groups. In addition risk of disease pneumonia was evaluated by race and ethnicity.(197) (197) (197)RESULTS The incidence of a first pneumonia episode in the control group was 55.9 per 1000 person-years. A radiograph was obtained in 61% of episodes, a positive radiograph in 21% and perihilar findings in an additional 5%. In per protocol follow-up of children given PCV, first episodes of all clinically diagnosed pneumonia were reduced by 4.3% [95% confidence interval (CI), -3.5, 11.5%, = 0.27], episodes with a radiograph were reduced by 9.8% (CI 0.1, 18.5%, < 0.05) and episodes with a positive radiograph were reduced by 20.5% (CI 4.4, 34.0, = 0.02). In the intent to treat analysis including all episodes after randomization, episodes with a positive radiograph were reduced by 17.7%, =.01). The greatest impact was in the first year of life with a 32.2% reduction and a 23.4% reduction in the first 2 years, but only a 9.1% reduction in children >2 years of age. Asians, blacks and Hispanics were at higher risk of pneumonia than were whites, but there was no evidence of ethnic variation in PCV effectiveness. Ten of the 11 cases of pneumococcal pneumonia with a positive blood culture were in the control group.CONCLUSION The pneumococcal conjugate vaccine tested was effective in reducing the risk of pneumonia in young children.

PMID: 12352800

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Vaccine 2002 Oct 4;20(29-30):3613
 

Immune responses against SIV envelope glycoprotein, using recombinant SV40 as a vaccine delivery vector.

McKee H, Strayer D

Department of Pathology and Cell Biology, Jefferson Medical College, 251 Jefferson Alumni Hall, 1020 Locust Street, 19107, Philadelphia, PA, USA

[Medline record in process]
 

Vaccination protocols using viral gene delivery vectors have often generated relatively weak responses, largely owing to difficulties in boosting immune responses effectively following the primary injection. Because recombinant gene delivery vectors derived from SV40 permit multiple inoculations, to yield incremental immune responses, we tested the use of rSV40s to deliver lentiviral envelope antigens for immunization. An rSV40 carrying SIVmac239 envelope glycoprotein gp130 cDNA (SV(gp130)) was given multiple times to BALB/c mice, with or without a prior priming inoculation using vaccinia virus carrying the same SIV envelope cDNA (VVenvSIV). Sera from these mice were tested for antibodies binding gp130, applying a novel cell-based ELISA protocol that used as targets cloned P815 cells stably transfected with plasmid-derived gp130 cDNA. The same gp130-expressing clone of P815 cells, labeled with 51Cr was used as targets for direct lymphocyte-mediated cytolytic assays using spleen and popliteal lymph node cells as effectors. After six inoculations with SV(gp130), mice made detectable anti-gp130 antibody responses, but high levels of splenic and popliteal lymph node cytotoxic activity were apparent after as few as three injections of SV(gp130) (>40% specific lysis). A single primary inoculation with VVenvSIV preceding SV(gp130) boosts significantly enhanced antibody responses against SIV gp130, but had little effect on cytotoxic lymphocyte responses. Thus, rSV40 vectors may be useful vehicles for delivering lentiviral envelope antigens to elicit protective humoral and cell-mediated immune responses.

PMID: 12297408, UI: 22234470

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Vaccine 2002 Oct 4;20(29-30):3598
 

Immunological monitoring during therapeutic vaccination as a prerequisite for the design of new effective therapies: induction of a vaccine-specific CD4+ T-cell proliferative response in chronic hepatitis B carriers.

Jung M, Gruner N, Zachoval R, Schraut W, Gerlach T, Diepolder H, Schirren C, Page M, Bailey J, Birtles E, Whitehead E, Trojan J, Zeuzem S, Pape G

Medical Department II, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, 81377, Munich, Germany

[Medline record in process]
 

We characterized the anti-viral T-cell response in 22 chronically infected patients, who participated in a European multi-center randomized placebo-controlled, double-blind study therapeutic vaccination trial with pre-S1, pre-S2 and S antigenic components of the hepatitis B virus (HBV). It induced a significant HBsAg-specific T-cell proliferation and the production of Th2-cytokines (i.e. IL-5). A specific induction of Th1-lymphokines was not detectable although this has been demonstrated in this study in response to the nucleocapsid protein (HBcAg). Further analysis indicated that this approach does not activate HBV-specific CD8+ T-lymphocytes as detected by ELISPOT-assay. Our results might explain why a specific therapeutic vaccine, although safe and well-tolerated is not always able to break tolerance leading to the clearance of the hepatitis B virus.

PMID: 12297407, UI: 22234469

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Vaccine 2002 Oct 4;20(29-30):3576
 

Generation and characterization of six single VP4 gene substitution reassortant rotavirus vaccine candidates: each bears a single human rotavirus VP4 gene encoding P serotype 1A[8] or 1B[4] and the remaining 10 genes of rhesus monkey rotavirus MMU18006 or bovine rotavirus UK.

Hoshino Y, Jones R, Chanock R, Kapikian A

Epidemiology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 50, Room 6308, 50 South Drive MSC 8026, 20892-8026, Bethesda, MD, USA

[Medline record in process]
 

The global disease burden of rotavirus diarrhea in infants and young children has stimulated interest in the biological and clinical characteristics of these agents, leading to intensive efforts to develop a vaccine. A rhesus rotavirus (RRV)-based quadrivalent vaccine ("RotaShield") was licensed and administered to about 1 million infants and found to be highly effective. However, it was withdrawn because of a link with intussusception. This vaccine was developed according to a modified "Jennerian" approach in which one of the two major outer capsid proteins (VP7) shares neutralization specificity with one of the four epidemiologically important human rotavirus serotypes. The other outer capsid protein (VP4) is derived solely from RRV and is distinct from the VP4 of the four human rotavirus serotypes of epidemiologic importance. In an effort to further increase the immunogenicity of the existing VP7-based RRV quadrivalent vaccine, we generated three single VP4 gene substitution reassortant rotavirus candidate vaccines, each of which bears a single human rotavirus VP4 gene encoding P serotype 1A[8] or 1B[4] specificity while the remaining 10 genes are derived from the rhesus rotavirus. By incorporating one or two of these strains into the quadrivalent vaccine, a pentavalent or hexavalent RRV-based vaccine could be formulated thus providing antigenic coverage not only for VP7 serotype 1, 2, 3 and 4 but also for VP4 serotype 1A[8] or 1B[4], thus possibly augmenting its immunogenicity. Similarly, three single VP4 gene (P1A[8] or P1B[4]) substitution reassortants have also been generated in a background of 10 bovine (UK) rotavirus genes for addition to a second generation UK-based quadrivalent vaccine.

PMID: 12297404, UI: 22234466

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Vaccine 2002 Oct 4;20(29-30):3569
 

An experimental vaccine for calf pneumonia caused by Mycoplasma bovis: clinical, cultural, serological and pathological findings.

Nicholas R, Ayling R, Stipkovits L

Mycoplasma Group, Department of Bacterial Diseases, Veterinary Laboratories Agency (Weybridge), Addlestone, KT15 3NB, Surrey, UK

[Medline record in process]
 

A single dose of vaccine for Mycoplasma bovis pneumonia, inactivated with saponin, was inoculated subcutaneously into 3-4 week-old calves. The calves were challenged 3 weeks later with a virulent strain of M. bovis on two occasions within 24h using the aerosol route. The calves were monitored for clinical signs and serological responses then post mortemed 3 weeks after challenge. The vaccine was shown to be highly immunogenic in calves and did not cause adverse effects. Vaccinated calves showed few clinical signs while all unvaccinated calves developed signs of pneumonia. There was a significant decrease in body weight gain in unvaccinated calves compared to vaccinates and a significant increase in lung lesions and rectal temperatures in unvaccinated calves. The vaccine also reduced the spread of M. bovis to internal organs. In conclusion the M. bovis vaccine produced a significant level of protection against a large virulent challenge.

PMID: 12297403, UI: 22234465

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Vaccine 2002 Oct 4;20(29-30):3560
 

Dual action ectoparasite vaccine targeting 'exposed' and 'concealed' antigens.

Trimnell A, Hails R, Nuttall P

CEH Institute of Virology and Environmental Microbiology, Mansfield Road, OX1 3SR, Oxford, UK

[Medline record in process]
 

Blood-feeding ectoparasites, such as mosquitoes, sandflies and ticks, transmit many disease agents. Their control relies on large-scale, repeated use of chemical pesticides. An alternative, targeted and environmentally friendly approach is to develop anti-ectoparasite vaccines. We describe a vaccine to control ticks that targets an 'exposed' tick saliva antigen and cross-reacts with 'concealed' tick midgut antigens. Ticks feeding on immunised animals induced a cutaneous inflammatory response and increased antibody titer, while engorged ticks died following damage to their midgut. This dual action, acting at the feeding site and in the midgut, offers a self-sustaining strategy for ectoparasite control boosted by natural infestations.

PMID: 12297402, UI: 22234464

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Vaccine 2002 Oct 4;20(29-30):3551
 

The difficult quest for data on "vanishing" vaccine-preventable infections in Europe: the case of measles in Flanders (Belgium).

Beutels P, Van Damme P, Van Casteren V, Gay N, De Schrijver K, Meheus A

Centre for the Evaluation of Vaccination, Epidemiology and Community Medicine, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium

[Medline record in process]
 

We aimed to describe the impact of vaccination on the epidemiology of measles infection in Flanders (Belgium), to document probable vaccination coverage based on this evidence, compare these epidemiological data with those generated by a mathematical model and estimate the costs of morbidity from measles. In contrast to previous analyses, we included the costs of long-term care for sequelae due to encephalitis and subacute sclerosing panencephalitis (SSPE). We estimated the direct health care costs per average measles case at 227, 212, 210, 200 and 194 for the age groups of 0-4, 5-9, 10-14, 15-19 and >/=20 years, respectively. Excluding long-term care lowers these estimates by 22-51%, depending on the age group. By including indirect time costs, we arrive at total costs per measles case of 320, 305, 210, 200 and 625, respectively. In addition to registering vaccination coverage more rigorously in the future, it seems necessary to undertake seroprevalence studies to document the age-specific immunity to measles. By using such information, current vaccination strategies can be adapted to prevent future outbreaks and to help eliminate measles from Europe in an efficient way. We noted throughout that many of the data sources are flawed. Better and accessible data bases are required to improve the reliability of similar studies in the future.

PMID: 12297401, UI: 22234463

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Vaccine 2002 Oct 4;20(29-30):3535
 

Comparison of the bioactivity of reference preparations for assaying Bordetella pertussis toxin activity in vaccines by the histamine sensitisation and Chinese hamster ovary-cell tests: assessment of validity of expression of activity in terms of protein concentration.

Xing D, Das R, Newland P, Corbel M

Division of Bacteriology, National Institute for Biological Standards and Control, Blanche Lane South Mimms, Hertfordshire, EN6 3QG, Potters Bar, UK

[Medline record in process]
 

Pertussis toxin (PT) in its detoxified form is an important antigenic component of both acellular and whole cell pertussis vaccines. Limits on the content of active PT in acellular vaccines are set in official monographs (EP, WHO, USP) and evidence of compliance is therefore, required by regulatory authorities. The two assay methods which are currently used by most manufacturers and official national control laboratories to monitor residual PT activity in acellular pertussis vaccines (and also in whole cell vaccines) are histamine sensitising (HIST) assays and Chinese hamster ovary (CHO) cell assays. Currently, different reference preparations of PT are used by individual laboratories for these tests. We therefore organised an international collaborative study to examine, by these two assay methods, two freeze-dried purified preparations of PT, one preparation in ampoules coded JNIH-5 and one preparation in ampoules coded 90/518, together with in-house reference (IHR) preparations in current use. Data from this study confirm that both JNIH-5 and 90/518 show biological activity both in HIST assays and in CHO-cell assays. Both HSD50 and ED50 values obtained in this study differ significantly between laboratories and thus show that biological activity is not determined by the nominal masses of preparations. Estimates of relative potency of 90/518 in terms of JNIH-5 per ampoule for the HIST assays do not differ significantly between laboratories. The overall mean estimates of relative potency of 90/518 in terms of JNIH-5 do not differ significantly between the two methods. Data from this study further indicate that the biological activity of different preparations was not directly related to their stated protein content. The use of protein content to indicate the level of PT activity in different preparations would give misleading results. Thus, use of a common standard is shown to greatly improve between laboratory agreement of estimates.

PMID: 12297399, UI: 22234461

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Vaccine 2002 Oct 4;20(29-30):3532
 

Effect of Pneumovax((R)) II vaccination in high-risk individuals on specific antibody and opsonic capacity against specific and non-specific antigen.

Huo Z, Miles J, Harris T, Riches P

Department of Biochemistry and Immunology, St. George's Hospital Medical School, Cranmer Terrace, SW17 0RE, London, UK

[Medline record in process]
 

Pneumovax((R)) II vaccine has been used in many countries including the UK for adults in high-risk groups to prevent pneumococcal infections. However, its effectiveness has been a controversial issue. In this study, the specific antibody concentration and opsonic capacity of serum against specific and non-specific antigens were measured in 16 high-risk adults vaccinated with Pneumovax((R)) II. The results indicated that 38% of these individuals could make an antibody response to specific antigens post-vaccination; vaccination had a clear effect in increasing the opsonic capacity of serum against specific pneumococcal antigen (S14 serotype) in 31% of patients, but did not have any effect against non-specific antigen. The specific antibody concentration did not significantly positively correlate with the opsonic capacity of serum. Therefore, it is concluded that the protective effect of Pneumovax((R)) II vaccination against a specific serotype in high-risk individuals will only be around 30%.

PMID: 12297398, UI: 22234460

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Vaccine 2002 Oct 4;20(29-30):3509
 

Physico-chemical and immunological examination of the thermal stability of tetanus toxoid conjugate vaccines.

Ho M, Mawas F, Bolgiano B, Lemercinier X, Crane D, Huskisson R, Corbel M

Bacteriology Division, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Herts., EN6 3QG, Potters Bar, UK

[Medline record in process]
 

The thermal stability of meningococcal C (MenC)- and Haemophilus influenzae b (Hib)-tetanus toxoid (TT) conjugate vaccines was investigated using spectroscopic and chromatographic techniques and immunogenicity assays in animal models. In this stability study, both the bulk concentrate and final fills were incubated at -20, 4, 23, 37 or 55 degrees C for 5 weeks or subjected to cycles of freeze-thawing. The structural stability, hydrodynamic size and molecular integrity of the treated vaccines were monitored by circular dichroism (CD), fluorescence and nuclear magnetic resonance (NMR) spectroscopic techniques, size exclusion chromatography (FPLC-SEC), and high performance anion exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD). Only storage at 55 degrees C for 5 weeks caused some slight unfolding and modification in the tertiary structure of the carrier protein in the MenC-TT conjugate. Substantial loss of saccharide content from the MenC conjugates was observed at 37 and 55 degrees C. Unexpectedly, the experimental immunogenicity of MenC-TT vaccine adsorbed to Alhydrogel was significantly reduced only by repeated freeze-thawing, but not significantly decreased by thermal denaturation. Neither the molecular integrity nor the immunogenicity of the lyophilised Hib-TT vaccines was significantly affected by freeze-thawing or by storage at high temperature. In conclusion, the MenC- and Hib-TT conjugate vaccines were relatively stable when stored at higher temperatures, though when MenC-TT vaccine was adsorbed to Alhydrogel, it was more vulnerable to repeated freeze-thawing. When compared with CRM(197) conjugate vaccines studied previously using similar techniques, the tetanus toxoid conjugates were found to have higher relative thermal stability in that they retained immunogenicity following storage at elevated temperatures.

PMID: 12297396, UI: 22234458

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Vaccine 2002 Oct 4;20(29-30):3485
 

Vaccination of puppies born to immune dams with a canine adenovirus-based vaccine protects against a canine distemper virus challenge.

Fischer L, Tronel J, Pardo-David C, Tanner P, Colombet G, Minke J, Audonnet J

Merial SAS, Biological Discovery Research, 254 rue Marcel Merieux, 69007, Lyon, France

[Medline record in process]
 

None of the currently available distemper vaccines provides a satisfactory solution for the immunization of very young carnivores in the face of maternal-derived immunity. Since mucosal immunization with replication-competent adenovirus-based vaccines has been proven effective in the face of passive immunity against the vector, it has the potential to provide a solution for the vaccination of young puppies born to canine distemper virus (CDV)-immune dams. We report the engineering and the characterization of two replication-competent canine adenovirus type 2 (CAV2)-based vaccines expressing, respectively, the CDV hemagglutinin (HA) and fusion (F) antigens. We first demonstrated that the intranasal vaccination with a mixture of both recombinant CAV2s provides an excellent level of protection in seronegative puppies, confirming the value of replication-competent adenovirus-based vectors for mucosal vaccination. In contrast, intranasal immunization with the same vaccine of puppies born to CDV- and CAV2-immune dams, failed to activate specific and protective immune responses. We hypothesized that an active CAV2 infection occurred while puppies were in close contact with the vaccinated dams in the breeding units and that the resulting active mucosal immunity interfered with the intranasal administration of CAV2-based CDV vaccine. However, when puppies born to CDV- and CAV2-immune dams were vaccinated subcutaneously with the CAV2-based CDV vaccine, significant seroconversion and solid protective immunity were triggered despite pre-existing systemic immunity to the vector. This latter result is surprising and suggests that subcutaneous vaccination with a replication-competent recombinant CAV2 may be an efficient strategy to overcome both passive and active adenovirus specific immunity in the dog. From a practical point of view, this could pave the way for an original strategy to vaccinate young puppies in the face of maternal-derived immunity.

PMID: 12297394, UI: 22234456

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Vaccine 2002 Oct 4;20(29-30):3472
 

A novel hepatitis B vaccination regimen for adolescents: two doses 12 months apart.

Heron L, Chant K, Jalaludin B

South Western Sydney Public Health Unit, Liverpool Hospital, Locked Bag 7017, NSW 1871, Sydney, Australia

[Record supplied by publisher]
 

BACKGROUND: Two- and three-dose hepatitis B vaccinations for adolescents are usually administered using dosing schedules of 6 months duration. This does not suit all circumstances. A 12-month schedule would be useful in schools and settings where only annual vaccination is the most practical option.AIM: To examine the efficacy of a 12-month dosing interval for two-dose hepatitis B vaccination of adolescents.SUBJECTS: Four hundred and fifty-eight healthy first-year high school (Year 7) students.VACCINATION REGIMEN: Engerix-B (GlaxoSmithKline Biologicals) 20&mgr;g: two doses, 12 months apart.SERUM COLLECTION: #1, same day as first vaccine dose given; #2, >1 month after second vaccine dose.RESULTS: Of the 458 children: 15 did not provide serum #1, 17 had prior vaccination, 2 had prior infection, 18 moved, 7 failed to provide serum #2, 12 withdrew (only 1 cited vaccine adverse reactions as the reason). Three hundred and eighty-seven (210 males, 177 females) aged 11.8-14.2 years (mean: 12.9+/-0.42 years) at entry completed both injections 321-381 days (mean: 359+/-10.7 days) apart and supplied serum #2, 30-57 days (mean: 41+/-5.6 days) after the second vaccine dose.Anti-HBs responses: 379 of the 387 subjects (97.9%; 95% CI: 95.9-99.1%) achieved anti-HBs >/=10mIU/ml (range 10-170,460mIU/ml, geometric mean concentration (GMC) 4155mIU/ml-95% CI of mean: 3381-5106mIU/ml). Sex was the only determinant of anti-HBs concentration (206 males: GMC 3073mIU/ml-95% CI: 2285-4134mIU/ml; 173 females: GMC 5944mIU/ml-95% CI: 4508-7851mIU/ml; P=0.001).CONCLUSION: A high seroprotection rate and GMC were achieved using two 20&mgr;g doses of Engerix-B administered 12 months apart. These results are similar to those achieved by others using 6-month three- and two-dose regimens in adolescents.

PMID: 12297392

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Vaccine 2002 Oct 4;20(29-30):3465
 

Mice vaccinated with the O-antigen of Francisella tularensis LVS lipopolysaccharide conjugated to bovine serum albumin develop varying degrees of protective immunity against systemic or aerosol challenge with virulent type A and type B strains of the pathogen.

Conlan J, Shen H, Webb A, Perry M

National Research Council Canada, Institute for Biological Sciences, Ont., K1A OR6, Ottawa, Canada

[Medline record in process]
 

The purpose of this study was to evaluate the efficacy of a vaccine consisting of the O-polysaccharide of the lipopolysaccharide (LPS) of Francisella tularensis chemically conjugated to bovine serum albumin. The results show that conjugation preserved both the antigenicity and immunogenicity of the polysaccharide moiety. Mice vaccinated with the glyco-conjugate, but not with BSA alone, were completely protected against an intradermal challenge with a highly virulent type B strain of F. tularensis, and partially protected against an aerosol challenge with the same strain. However, such vaccination failed to protect against an aerosol challenge with a virulent type A strain of the pathogen. The results suggest that the O-antigen of F. tularensis could be considered as a potential component of a subunit vaccine against type B, but not type A strains of F. tularensis.

PMID: 12297391, UI: 22234453

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Vaccine 2002 Oct 4;20(29-30):3456
 

Enhancement of human papillomavirus (HPV) type 16 E6 and E7-specific T-cell immunity in healthy volunteers through vaccination with TA-CIN, an HPV16 L2E7E6 fusion protein vaccine.

de Jong A, O'Neill T, Khan A, Kwappenberg K, Chisholm S, Whittle N, Dobson J, Jack L, St Clair Roberts J, Offringa R, van der Burg S, Hickling J

Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, P.O. Box 9600, 2300 RC, Leiden, The Netherlands

[Record supplied by publisher]
 

TA-CIN is a vaccine that comprises the human papillomavirus (HPV) type 16 L2, E6 and E7 as a single fusion protein. In a mouse model, TA-CIN effectively prevented outgrowth of HPV16-positive tumour cells. To assess the safety and immunogenicity of TA-CIN, a dose escalating (26, 128, 533&mgr;g), double blind and placebo-controlled phase I study was conducted in 40 healthy volunteers. TA-CIN was administered without adjuvant by intramuscular injection on weeks 0, 4 and 8. No serious adverse events of the vaccination were reported during the study. Both IgG antibodies and proliferative responses against TA-CIN were elicited at all three doses. More importantly, T-cell immunity against the HPV16 E6 and E7 oncoproteins was detected by IFNgamma ELISPOT in 8/11 evaluable subjects vaccinated with the 533&mgr;g dose.

PMID: 12297390

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Vaccine 2002 Oct 4;20(29-30):3443
 

Characterization of protective immune responses induced by nasal influenza vaccine containing mutant cholera toxin as a safe adjuvant (CT112K).

Watanabe I, Hagiwara Y, Kadowaki S, Yoshikawa T, Komase K, Aizawa C, Kiyono H, Takeda Y, McGhee J, Chiba J, Sata T, Kurata T, Tamura S

Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, 162-8640, Tokyo, Japan

[Record supplied by publisher]
 

Immune responses induced by a nasal influenza vaccine with a mutant cholera toxin (CT112K), known to be a safe adjuvant, were characterized in BALB/c mice to confirm the most suitable regimen of this vaccine for humans. Mice received a primary intranasal administration of the adjuvant (0.1&mgr;g)-combined PR8 vaccine (0.1&mgr;g) and a secondary administration of the PR8 vaccine alone (0.1&mgr;g) 4 weeks later. Two weeks after the secondary immunization, the mice were infected with a nonlethal or a lethal dose of PR8 viruses. Nasal and lung wash virus titers 1 or 3 days after infection indicated that complete protection could be provided by secondary immune responses, which had an immediate effect of preventing infection 2 weeks after the secondary immunization. In this two-dose regimen, high levels of secondary IgA, IgG and IgM antibody-forming cell (AFC) responses were induced in the nasal-associated lymphoid tissue and the spleen. In parallel with the AFC responses, high levels of nasal wash anti-PR8 HA IgA, and lung and serum IgG antibody (Ab) responses were induced 2 weeks after the secondary immunization. The two-dose regimen also induced accelerated delayed-type hypersensitivity responses, which exhibited almost the same peak height as that in the case of the primary response. In addition, the two-dose regimen induced a low memory cell activity of cytotoxic T lymphocytes, detected by in vitro culture of spleen cells. Thus, the immediate effect of preventing infection was mainly provided by the secondary Ab responses. Moreover, the levels of nasal wash IgA Abs correlated well with cross-protection against infection with variant viruses in the upper respiratory tract (RT). These results suggest that the major protective factors among Ab and T cell-mediated immune responses, which are induced by the two-dose regimen using CT112K-combined vaccines, are the cross-reactive IgA Abs in the upper RT and the less cross-reactive IgG Abs in the lower RT, and that the two-dose regimen is a suitable vaccination condition for humans.

PMID: 12297389

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Vaccine 2002 Oct 4;20(29-30):3431
 

Immune response to an indigenously developed hepatitis-B (Shanvac-B) vaccine in a tribal community of India.

Murhekar M, Murhekar K, Arankalle V, Sehgal S

Regional Medical Research Centre, Indian Council of Medical Research, Post Bag 13, 744-101, Andaman and Nicobar Islands, Port Blair, India

[Medline record in process]
 

Hepatitis-B infection is highly endemic among the primitive tribes of Andaman and Nicobar Islands, India. A pilot project of hepatitis-B vaccination using indigenously developed (Shanvac-B) was initiated among the Nicobarese tribe in Car Nicobar Island. The 936 individuals negative for HBsAg and anti-HBs were administered three doses of the vaccine at 0, 1 and 6 months. The vaccine was found to be safe and efficacious with sero-protection rates of 49.1, 86.9 and 96.7% after first, second and third dose. Considering the high endemicity of the infection and small number of the tribal population, it is necessary to initiate hepatitis-B vaccination programme for this community. Since the vaccine was found to be cost-effective, it could be adopted for hepatitis-B vaccination in this community.

PMID: 12297387, UI: 22234449

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Vaccine 2002 Feb 22;20(11-12):1660-9
 

Immunogenicity of the Brucella melitensis recombinant ribosome recycling factor-homologous protein and its cDNA.

Cassataro J, Velikovsky CA, Giambartolomei GH, Estein S, Bruno L, Cloeckaert A, Bowden RA, Spitz M, Fossati CA

Facultad de Farmacia y Bioquimica, Instituto de Estudios de la Inmunidad Humoral (IDEHU), Universidad de Buenos Aires (UBA), Junin 956, 1113 Buenos Aires, Argentina.

A study was conducted to evaluate the immunogenicity of the Brucella melitensis ribosome recycling factor (RRF)-homologous protein (CP24). The CP24 gene was cloned, expressed in Escherichia coli and purified. The resulting purified recombinant protein (rCP24) produced delayed-type hypersensitivity (DTH) reactions in B. melitensis-infected mice but not in naive controls. Thus, we decided to characterise the immune responses generated with DNA vaccination (pcDNACP24) or immunisation with the rCP24 in adjuvant. Animals injected with pcDNACP24 exhibited a dominance of IgG2a to IgG1 while mice injected with rCP24 developed a higher response of IgG1 than IgG2a. Both immunisation protocols were capable of eliciting CP24-specific gamma interferon (IFN-gamma) producing cells. Spleen cells from pcDNACP24-immunised mice did not produce interleukin (IL)-4, IL-10 or up-regulation of IL-2 mRNA. Cells from rCP24-immunised mice produced IL-10, up-regulated IL-2 mRNA but did not produce IL-4. Neither immunisation with purified CP24 nor injection of pcDNACP24 protected mice against challenge with live smooth B. melitensis. However, the potential of CP24 for a Brucella diagnostic test based on an in vitro antigen (Ag)-specific IFN-gamma production or DTH test would be worth testing.

PMID: 11858876, UI: 21848605

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Vaccine 2002 Feb 22;20(11-12):1653-9
 

Nasal mucosal immunogenicity for the horse of a SeM peptide of Streptococcus equi genetically coupled to cholera toxin.

Sheoran AS, Artiushin S, Timoney JF

Gluck Equine Research Center, University of Kentucky, Lexington, KY 40546-0099, USA.

The intranasal immunogenicity of cholera toxin (CT) genetically coupled to peptide sequence aa236-334 (F3) of the SeM protein of Streptococcus equi was studied in five young adult Welsh ponies. All ponies made rapid CTB- and SeMF3-specific serum antibody responses following the first immunization. Specific nasal IgA responses were detected in two ponies 14 days after the first immunization, in another two 14 days after a second immunization on day 14, and in all ponies 28 days after a third immunization on day 42. SeMF3-specific antibody responses in sera and nasal washes were dominated by IgGb and IgA, respectively, and remained elevated for at least 140 days. Strong serum IgGa and IgG(T) responses were also observed. These antibody responses were qualitatively similar to those induced during recovery from equine strangles. Antibody responses in mucosal secretions were boosted in some ponies by immunizations subsequent to the first immunization, but antibodies in serum were never boosted. In vitro survival of S. equi was significantly reduced by SeMF3-specific antibodies in sera obtained 14 days after the second immunization but survival increased in sera collected following subsequent immunizations, possibly due to absence of synthesis of high affinity antibodies. Finally, the susceptibility of all immunized ponies to commingling challenge by S. equi indicated either that SeMF3 lacks protective epitopes or that the antibodies induced by the chimera were not at effective levels.

PMID: 11858875, UI: 21848604

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Vaccine 2002 Feb 22;20(11-12):1631-9
 

Early protection against homologous challenge after a single dose of replication-defective human adenovirus type 5 expressing capsid proteins of foot-and-mouth disease virus (FMDV) strain A24.

Moraes MP, Mayr GA, Mason PW, Grubman MJ

US Department of Agriculture, Agricultural Research Service, Plum Island Animal Disease Center, North Atlantic Area, P.O. Box 848, Greenport, NY 11944-0848, USA.

Previously we demonstrated that two doses of a replication-defective human adenovirus serotype 5 (Ad5) carrying the capsid (P1) and 3C protease coding regions of a laboratory strain of FMDV (A12) completely protected five of six swine challenged with homologous virus. The objective of the current study was to evaluate the efficacy of one dose of an Ad5-vectored vaccine expressing the P1 coding region of an FMDV field strain. A replication-defective Ad5 containing the P1 coding region of FMDV A24 and the 3C coding region of A12 (Ad5A24) was constructed and evaluated for its ability to induce neutralizing antibodies and protect swine against homologous challenge after a single vaccination. Animals were challenged 7, 14 or 42 days after vaccination. Control groups included animals inoculated with commercial vaccine or phosphate-buffered saline. All vaccinated swine were completely protected against homologous challenge at 7, 14 or 42 days after vaccination. Based on these results, we conclude that a single inoculation of Ad5-vectored vaccines could be used as a tool to control FMD in outbreak situations.

PMID: 11858872, UI: 21848601

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Vaccine 2002 Feb 22;20(11-12):1618-23
 

Immunogenicity of chi4127 phoP- Salmonella enterica serovar Typhimurium in dogs.

McVey DS, Chengappa MM, Mosier DE, Stone GG, Oberst RD, Sylte MJ, Gabbert NM, Kelly-Aehle SM, Curtiss R

Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA. d_scott_mcvey@groton.pfizer.com

Salmonellae are commonly isolated from dogs. The number of dogs infected with Salmonella spp. is surprisingly high and greater than the incidence of clinical disease would suggest. Salmonellosis is common in greyhound kennels. Morbidity can approach 100% in puppies and the mortality ranges to nearly 40%. To date, there has been little effort to evaluate the feasibility of a vaccine for control of this disease in dogs. In the studies described here, an attenuated strain of Salmonella enterica serovar Typhimurium (Se Typhimurium), chi4127, was capable of establishing a limited infection in dogs. The chi4127-attenuated salmonellae efficiently stimulated protective immune responses in serotype homologous, direct, oral challenge experiments. Morbidity in the wild-type-challenged dogs was 8.3% in immunized dogs but 100% in the non-vaccinated controls. In (9/12) control dogs, the disease involved both gastrointestinal and respiratory tracts with high fever (>40.2 degrees C) that persisted through 5 days after challenge. Serum IgG response against S. typhimurium lipopolysaccharide (LPS) significantly increased (P<0.01) in vaccinated dogs and in non-vaccinated dogs after challenge. The non-vaccinated dogs had 3 to 4 logs higher numbers of Se Typhimurium in splenic and hepatic tissue than did the vaccinated dogs. This particular attenuated strain has potential for use as a vaccine for canine salmonellosis.

PMID: 11858870, UI: 21848599

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Vaccine 2002 Feb 22;20(11-12):1579-85
 

Intranasal inoculation of a recombinant influenza virus containing exogenous nucleotides in the NS segment induces mucosal immune response against the exogenous gene product in mice.

Takasuka N, Enami M, Itamura S, Takemori T

Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan.

To establish a mucosal vaccine system, we evaluated the immunogenicity of a recombinant influenza virus, designated NS2Acat, in which the chloramphenicol acetyltransferase (CAT) reporter gene is fused in frame to the NS1 gene in the NS gene segment. The NS2Acat replicated slightly within the lungs in BALB/c mice after intranasal administration, accompanying expression of the CAT and the viral HA mRNA. NS2Acat induced delayed-type hypersensitivity (DTH) and sensitized the CAT-specific T lymphocytes in the regional lymph nodes, which proliferated and synthesized several cytokines in vitro upon antigenic challenge. These results suggest that NS2Acat is capable of eliciting a respiratory immune response against the fused gene product.

PMID: 11858865, UI: 21848594

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Vaccine 2002 Feb 22;20(11-12):1571-8
 

Immunization of T-cell deficient mice against polyomavirus infection using viral pseudocapsids or temperature sensitive mutants.

Heidari S, Vlastos A, Ramqvist T, Clark B, Griffin BE, Garcia MI, Perez M, Amati P, Dalianis T

Division of Experimental Oncology, Cancer Centre Karolinska, Karolinska Hospital, SE-17176 Stockholm, Sweden. shirin.heidari@mtc.ki.se

A murine experimental model system aimed at developing potential vaccines to papovavirus infection in immunosuppressed individuals was explored. A VP1-pseudocapsid based on the major capsid protein of the murine polyomavirus A2 strain and a mutant, M17-pseudocapsid as well as four temperature sensitive (ts)-mutants were used as immunogens. T-cells deficient CD4-/-8-/- mice were immunized four times with each immunogen and then together with non-immunized control mice challenged with polyomavirus. In contrast to all control mice, only half of the immunized mice exhibited presence of polyoma DNA when assayed by PCR. The results indicate that pseudocapsids and ts-mutant immunization may potentially protect mice with an impaired T-cell function from polyomavirus infection.

PMID: 11858864, UI: 21848593

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Vaccine 2002 Feb 22;20(11-12):1563-70
 

Protective efficacy of a plasmid DNA encoding Japanese encephalitis virus envelope protein fused to tissue plasminogen activator signal sequences: studies in a murine intracerebral virus challenge model.

Ashok MS, Rangarajan PN

Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.

We report the construction of chimeric DNA vaccine vectors in which secretory signal sequence derived from tissue plasminogen activator (TPA) was fused to the full length (pCMVTE) or 398 amino terminal amino acids (pCMVTdeltaE) of Japanese encephalitis virus (JEV) envelope (E) protein. Transfection studies indicate that E protein expressed from pCMVTdeltaE-transfected cells but not pCMVTE-transfected cells is secreted into the culture medium. Analysis of the potency of various DNA vaccine constructs in a murine intracerebral (i.c.) JEV challenge model indicates that pCMVTdeltaE confers the highest level (71%) of protection. Immunization with pCMVTdeltaE induces a mixed Th1 and Th2 T helper cell response while immunization with plasmids encoding nonsecretory forms of E protein induces a Th1 T helper response. Only low levels (<1:20) of virus neutralizing antibody titres were observed in DNA vaccinated mice which did not increase further after i.c. JEV challenge. Thus, immunization with a plasmid encoding secretory E protein results in an altered cytokine response and better protection against i.c. JEV challenge than that conferred by immunization with plasmids encoding nonsecretory forms of E protein. We also demonstrate that unlike peripheral JEV challenge, i.c. JEV challenge does not result in an increase in anamnestic antibody response suggesting that other components of immune system such as cytotoxic T cells and T helper cells contribute to protection against i.c. JEV challenge of DNA vaccinated mice.

PMID: 11858863, UI: 21848592

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Vaccine 2002 Feb 22;20(11-12):1532-40
 

Application of heat killed Mycobacterium bovis-BCG into the lung inhibits the development of allergen-induced Th2 responses.

Major T, Wohlleben G, Reibetanz B, Erb KJ

Centre for Infectious Diseases, University of Wurzburg, Rontgenring 11, 97070 Wurzburg, Germany.

We have previously reported that an infection of the lung with BCG-inhibited ovalbumin (OVA)-induced airway eosinophilia. In the current study, we investigated if the intranasal application of heat killed (HK)-BCG or purified protein derivative (PPD) from Mycobacterium tuberculosis had the same effect. For this purpose we treated mice intranasally with either live BCG, HK-BCG or PPD and analyzed if the mice developed airway eosinophilia after immunization and intranasal challenge with OVA. Our results clearly showed that an intranasal vaccination with live and HK-BCG but not PPD, given 4 or 8 weeks prior to allergen airway challenge, resulted in a strong suppression of airway eosinophilia. The inhibition of airway eosinophilia correlated with reduced levels of IL-5 production by T cells from the lymph node of the lungs and a strong reduction in Th2 cell numbers present in the airways of OVA-challenged mice. Furthermore, HK-BCG-induced suppression of airway eosinophilia was strongly reduced in IFN-gamma deficient mice. HK-BCG in contrast to live BCG may also be a promising candidate for a prospective asthma vaccine in humans since negative side effects due to mycobacterial infection can be ruled out.

PMID: 11858859, UI: 21848588

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Wkly Epidemiol Rec 2002 Sep 13;77(37):305-11
 

Vaccines and biologicals. Recommendations from the Strategic Advisory Group of Experts.

[Medline record in process]
 

PMID: 12298104, UI: 22234825

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