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Infect Immun 2002 Aug;70(8):4621-7
 

Effects of Oral Vaccination and Immunomodulation by Cholera Toxin on Experimental Helicobacter pylori Infection, Reinfection, and Gastritis.

Raghavan S, Svennerholm AM, Holmgren J

Department of Medical Microbiology and Immunology and Goteborg University Vaccine Research Institute, Goteborg University, S 41346 Goteborg, Sweden.

[Medline record in process]
 

Therapeutic vaccination is an attractive strategy to control infection and disease caused by Helicobacter pylori. In mice infected with H. pylori we have studied the protective effect of oral immunization with an H. pylori lysate preparation given together with the mucosal adjuvant cholera toxin (CT), both against the initial infection and against a later reinfection challenge. We have also examined the effects of treatment with the CT adjuvant alone on H. pylori infection and reinfection. Specific immunization with lysate was found to result in a sixfold reduction of the extent (bacterial load) of the primary infection and also to provide similar levels of protection against reinfection. However, these effects were associated with severe postimmunization gastritis. In contrast, oral treatment with CT alone at the time of initial infection, while unable to suppress the initial infection, gave rise to a 20-fold reduction in bacterial load upon reinfection without causing any associated gastric inflammation. Both the infected animals that were specifically immunized and those that were treated with CT only displayed increased in vitro proliferative responses of mononuclear cells to H. pylori antigens. Antibody levels in response to H. pylori were on the other hand only marginally increased after treatment with CT, whereas they were markedly elevated after immunization with lysate plus CT, with a rise in both (Th2-driven) immunoglobulin G1 (IgG1) and, especially, (Th1-driven) IgG2a antibodies. The results illustrate the complex balance between protection and harmful inflammation after postinfection vaccination against H. pylori as studied in a mouse model.

PMID: 12117975, UI: 22112912

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Infect Immun 2002 Aug;70(8):4600-8
 

Quantitative priming with inactivated pertussis toxoid vaccine in the aerosol challenge model.

Bruss JB, Siber GR

Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.

[Medline record in process]
 

Serum antibodies to pertussis toxin (PT) have been shown to be protective against severe pertussis disease, although a specific level of anti-PT antibody that correlates with protection has not been demonstrated. Current animal models such as the intracerebral challenge model have significant limitations in correlating protection to a specific level of anti-PT antibody. This study examines the protective effects of priming with tetranitromethane-inactivated pertussis toxoid (PTx) vaccine in the aerosol challenge model and whether a measurable response to a priming dose of PTx is enough to initiate a protective secondary response when challenged with infection. The correlation of priming with markers of illness such as leukocytosis, weight loss, bacterial proliferation, and mortality after established infection with Bordetella pertussis was explored. BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. Data were analyzed according to the primary immunologic response, differentiating responders (anti-PT immunoglobulin G [IgG] >/=1 microg/ml) from nonresponders (anti-PT IgG <1 microg/ml). Mice that showed evidence of priming on the day of aerosol challenge were able to mount a secondary response to the challenge with a >/=2-fold rise in anti-PT IgG antibody by day 7 and a >/=10-fold rise by day 14 post-aerosol challenge. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge.

PMID: 12117973, UI: 22112910

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Infect Immun 2002 Aug;70(8):4471-6
 

High-Level Expression of the Malaria Blood-Stage Vaccine Candidate Plasmodium falciparum Apical Membrane Antigen 1 and Induction of Antibodies That Inhibit Erythrocyte Invasion.

Kocken CH, Withers-Martinez C, Dubbeld MA, Van Der Wel A, Hackett F, Blackman MJ, Thomas AW

Department of Parasitology, Biomedical Primate Research Centre, 2280 GH Rijswijk, The Netherlands. Division of Parasitology. Division of Protein Structure, National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom.

[Medline record in process]
 

Apical membrane antigen 1 (AMA-1) is a highly promising malaria blood-stage vaccine candidate that has induced protection in rodent and nonhuman primate models of malaria. Authentic conformation of the protein appears to be essential for the induction of parasite-inhibitory antibody responses. Here we have developed a synthetic gene with adapted codon usage to allow expression of Plasmodium falciparum FVO strain AMA-1 (PfAMA-1) in Pichia pastoris. In addition, potential N-glycosylation sites were changed, exploiting the lack of conservation of these sites in Plasmodium, to obtain high-level secretion of a homogeneous product, suitable for scale-up according to current good manufacturing procedures. Purified PfAMA-1 displayed authentic antigenic properties, indicating that the amino acid changes had no deleterious effect on the conformation of the protein. High-titer antibodies, raised in rabbits, reacted strongly with homologous and heterologous P. falciparum by immunofluorescence. In addition, purified immunoglobulin G from immunized animals strongly inhibited invasion of red blood cells by homologous and, to a somewhat lesser extent, heterologous P. falciparum.

PMID: 12117958, UI: 22112895

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Infect Immun 2002 Aug;70(8):4414-23
 

Molecular cloning and characterization of genes for Shigella sonnei form I O polysaccharide: proposed biosynthetic pathway and stable expression in a live salmonella vaccine vector.

Xu DQ, Cisar JO, Ambulos Jr N Jr, Burr DH, Kopecko DJ

Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.

[Medline record in process]
 

The gene region for biosynthesis of Shigella sonnei form I O polysaccharide (O-Ps) and flanking sequences, totaling >18 kb, was characterized by deletion analysis to define a minimal construct for development of Salmonella-based live vaccine vector strains. Lipopolysaccharide (LPS) expression and DNA sequence studies of plasmid deletion derivatives indicated form I O-Ps expression from a 12.3-kb region containing a putative promoter and 10 contiguous open reading frames (ORFs), one of which is the transposase of IS630. A detailed biosynthetic pathway, consistent with the predicted functions of eight of the nine essential ORFs and the form I O-Ps structure, is proposed. Further sequencing identified partial IS elements (i.e., IS91 and IS630) and wzz upstream of the form I coding region and a fragment of aqpZ and additional full or partial IS elements (i.e., IS629, IS91, and IS911) downstream of this region. The stability of plasmid-based form I O-Ps expression was greater from low-copy vectors than from high-copy vectors and was enhanced by deletion of the downstream IS91 from plasmid inserts. Both core-linked (i.e., LPS) and non-core-linked (i.e., capsule-like) surface expression of form I O-Ps were detected by Western blotting and silver staining of polyacrylamide gel electrophoresis-separated Shigella and Escherichia coli extracts. However, salmonellae, which have a core that is chemically dissimilar to that of shigellae, expressed only non-core-linked surface-associated form I O-Ps. Finally, attenuated Salmonella enterica serovar Typhi live vaccine vector candidates, containing minimal-sized form I operon constructs, elicited immune protection in mice against virulent S. sonnei challenge, thereby supporting the promise of live, oral vaccines for the prevention of shigellosis.

PMID: 12117952, UI: 22112889

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Infect Immun 2002 Aug;70(8):4215-25
 

Immunization with a Polyprotein Vaccine Consisting of the T-Cell Antigens Thiol-Specific Antioxidant, Leishmania major Stress-Inducible Protein 1, and Leishmania Elongation Initiation Factor Protects against Leishmaniasis.

Coler RN, Skeiky YA, Bernards K, Greeson K, Carter D, Cornellison CD, Modabber F, Campos-Neto A, Reed SG

Infectious Disease Research Institute. Corixa Corporation, Seattle, Washington 98104.

[Medline record in process]
 

Development of an effective vaccine against Leishmania infection is a priority of tropical disease research. We have recently demonstrated protection against Leishmania major in the murine and nonhuman primate models with individual or combinations of purified leishmanial recombinant antigens delivered as plasmid DNA constructs or formulated with recombinant interleukin-12 (IL-12) as adjuvant. In the present study, we immunized BALB/c mice with a recombinant polyprotein comprising a tandem fusion of the leishmanial antigens thiol-specific antioxidant, L. major stress-inducible protein 1 (LmSTI1), and Leishmania elongation initiation factor (LeIF) delivered with adjuvants suitable for human use. Aspects of the safety, immunogenicity, and vaccine efficacy of formulations with each individual component, as well as the polyprotein referred to as Leish-111f, were assessed by using the L. major challenge model with BALB/c mice. No adverse reactions were observed when three subcutaneous injections of the Leish-111f polyprotein formulated with either MPL-squalene (SE) or Ribi 529-SE were given to BALB/c mice. A predominant Th1 immune response characterized by in vitro lymphocyte proliferation, gamma interferon production, and immunoglobulin G2A antibodies was observed with little, if any, IL-4. Moreover, Leish-111f formulated with MPL-SE conferred immunity to leishmaniasis for at least 3 months. These data demonstrate success at designing and developing a prophylactic leishmaniasis vaccine that proved effective in a preclinical model using multiple leishmanial antigens produced as a single protein delivered with a powerful Th1 adjuvant suitable for human use.

PMID: 12117930, UI: 22112867

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Infect Immun 2002 Aug;70(8):4009-18
 

Salmonella enterica Serovar Typhi Live Vector Vaccines Delivered Intranasally Elicit Regional and Systemic Specific CD8(+) Major Histocompatibility Class I-Restricted Cytotoxic T Lymphocytes.

Pasetti MF, Salerno-Goncalves R, Sztein MB

Center for Vaccine Development, Department of Pediatrics. Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201.

[Medline record in process]
 

We investigated the ability of live attenuated Salmonella enterica serovar Typhi strains delivered to mice intranasally to induce specific cytotoxic T-lymphocyte (CTL) responses at regional and systemic levels. Mice immunized with two doses (28 days apart) of Salmonella serovar Typhi strain Ty21a, the licensed oral typhoid vaccine, and genetically attenuated mutants CVD 908 (DeltaaroC DeltaaroD), CVD 915 (DeltaguaBA), and CVD 908-htrA (DeltaaroC DeltaaroD DeltahtrA) induced CTL specific for Salmonella serovar Typhi-infected cells in spleens and cervical lymph nodes. CTL were detected in effector T cells that had been expanded in vitro for 7 days in the presence of Salmonella-infected syngeneic splenocytes. A second round of stimulation further enhanced the levels of specific cytotoxicity. CTL activity was observed in sorted alphabeta(+) CD8(+) T cells, which were remarkably increased after expansion, but not in CD4(+) T cells. CTL from both cervical lymph nodes and spleens failed to recognize Salmonella-infected major histocompatibility complex (MHC)-mismatched cells, indicating that the responses were MHC restricted. Studies in which MHC blocking antibodies were used showed that H-2L(d) was the restriction element. This is the first demonstration that Salmonella serovar Typhi vaccines delivered intranasally elicit CD8(+) MHC class I-restricted CTL. The results further support the usefulness of the murine intranasal model for evaluating the immunogenicity of typhoid vaccine candidates at the preclinical level.

PMID: 12117906, UI: 22112843

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J Immunol 2002 Jun 15;168(12):6463-9
 

Resistance to adjuvant arthritis is due to protective antibodies against heat shock protein surface epitopes and the induction of IL-10 secretion.

Ulmansky R, Cohen CJ, Szafer F, Moallem E, Fridlender ZG, Kashi Y, Naparstek Y

Clinical Immunology and Allergy Unit, Hadassah University Hospital, Jerusalem, Israel.

Adjuvant arthritis (AA) is an experimental model of autoimmune arthritis that can be induced in susceptible strains of rats such as inbred Lewis upon immunization with CFA. AA cannot be induced in resistant strains like Brown-Norway or in Lewis rats after recovery from arthritis. We have previously shown that resistance to AA is due to the presence of natural as well as acquired anti-heat shock protein (HSP) Abs. In this work we have studied the fine specificity of the protective anti-HSP Abs by analysis of their interaction with a panel of overlapping peptides covering the whole HSP molecule. We found that arthritis-susceptible rats lack Abs to a small number of defined epitopes of the mycobacterial HSP65. These Abs are found naturally in resistant strains and are acquired by Lewis rats after recovery from the disease. Active vaccination of Lewis rats with the protective epitopes as well as passive vaccination with these Abs induced suppression of arthritis. Incubation of murine and human mononuclear cells with the protective Abs induced secretion of IL-10. Analysis of the primary and tertiary structure of the whole Mycobacterium tuberculosis HSP65 molecule indicated that the protective epitopes are B cell epitopes with nonconserved amino acid sequences found on the outer surface of the molecule. We conclude that HSP, the Ag that contains the pathogenic T cell epitopes in AA, also contains protective B cell epitopes exposed on its surface, and that natural and acquired resistance to AA is associated with the ability to respond to these epitopes.

PMID: 12055266, UI: 22050789

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J Virol 2002 Jul;76(13):6669-77
 

Cross-protection against challenge with Puumala virus after immunization with nucleocapsid proteins from different hantaviruses.

de Carvalho Nicacio C, Gonzalez Della Valle M, Padula P, Bjorling E, Plyusnin A, Lundkvist A

Microbiology and Tumorbiology Center, Box 280, Karolinska Institutet, 171 77 Stockholm, Sweden. cristina.de.carvalho@mtc.kti.se

Hantaviruses are rodent-borne agents that cause hemorrhagic fever with renal syndrome or hantavirus pulmonary syndrome in humans. The nucleocapsid protein (N) is relatively conserved among hantaviruses and highly immunogenic in both laboratory animals and humans, and it has been shown to induce efficient protective immunity in animal models. To investigate the ability of recombinant N (rN) from different hantaviruses to elicit cross-protection, we immunized bank voles with rN from Puumala (PUUV), Topografov (TOPV), Andes (ANDV), and Dobrava (DOBV) viruses and subsequently challenged them with PUUV. All animals immunized with PUUV and TOPV rN were completely protected. In the group immunized with DOBV rN, 7 of 10 animals were protected, while only 3 of 8 animals were protected in the group immunized with ANDV rN, which is more closely related to PUUV rN than DOBV rN. Humoral and cellular immune responses after rN immunization were also investigated. The highest cross-reactive humoral responses against PUUV antigen were detected in sera from ANDV rN-immunized animals, followed by those from TOPV rN-immunized animals, and only very low antibody cross-reactivity was observed in sera from DOBV rN-immunized animals. In proliferation assays, T lymphocytes from animals immunized with all heterologous rNs were as efficiently recalled in vitro by PUUV rN as were T lymphocytes from animals immunized with homologous protein. In summary, this study has shown that hantavirus N can elicit cross-protective immune responses against PUUV, and the results suggest a more important role for the cellular arm of the immune response than for the humoral arm in cross-protection elicited by rN.

PMID: 12050380, UI: 22045645

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J Virol 2002 Jul;76(13):6652-9
 

Regulation of DNA-raised immune responses by cotransfected interferon regulatory factors.

Sasaki S, Amara RR, Yeow WS, Pitha PM, Robinson HL

Division of Microbiology and Immunology, Yerkes National Primate Research Center and Vaccine Research Center, Emory University School of Medicine, 954 Gatewood Road, Atlanta, GA 30329, USA.

Interferon regulatory factor 1 (IRF-1), IRF-3, and IRF-7 have been tested as genetic adjuvants for influenza virus hemagglutinin (HA) and nucleoprotein vaccine DNAs. Cotransfection of HA with IRF-3 and IRF-7 increased CD4 T-cell responses by 2- to 4-fold and CD8 T-cell responses by more than 10-fold. Following intramuscular deliveries of DNA, both CD4 and CD8 T cells were biased towards type 1 immune responses and the production of gamma interferon. Following gene gun bombardments of DNA, both were biased towards type 2 immune responses and the production of interleukin-4. The biases of the T-cell responses towards type 1 or type 2 were stronger for immunizations with IRF-3 as an adjuvant than for immunizations with IRF-7 as an adjuvant. Moderate adjuvant effects for antibody were observed. The isotypes of the antibody responses reflected the method of DNA delivery; intramuscular deliveries of DNA predominantly raised immunoglobulin G2a (IgG2a), whereas gene gun deliveries of DNA predominantly raised IgG1. These biases were enhanced by the codelivered IRFs. Overall, under the conditions of our experiments, IRF-3 had good activity for T cells, IRF-7 had good activity for both antibody and T cells, and IRF-1 had good activity for antibody.

PMID: 12050378, UI: 22045643

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J Virol 2002 Jul;76(13):6568-76
 

Induction of CD8 T-cell-specific systemic and mucosal immunity against herpes simplex virus with CpG-peptide complexes.

Gierynska M, Kumaraguru U, Eo SK, Lee S, Krieg A, Rouse BT

Department of Microbiology, Walters Life Sciences Building, University of Tennessee, Knoxville, TN 37996-0845, USA.

Oligodeoxynucleotides (ODN) containing unmethylated CpG motifs exert powerful adjuvant activity in vivo and in vitro. Administered with antigen they induce a population of antigen-specific CD8+ T cells. In this study we immunized C57BL/6 mice with bioactive CpG ODN combined with an immunodominant epitope derived from herpes simplex virus (HSV) glycoprotein B (amino acids 498 to 505; SSIEFARL) and analyzed the magnitude and durability of the peptide-specific response. The effectiveness of the CD8+ T-cell response as measured by peptide-specific tetramers, peptide-induced intracellular gamma interferon expression, and resistance to systemic and mucosal challenge during the acute and memory phases was compared with the response induced by immunization with recombinant vaccinia virus encoding SSIEFARL as a minigene (VvgB(498-505)). Confirming the reports of others, our results demonstrate that the CpG ODN-peptide approach generates an antigen-specific CD8+ T-cell population, but the frequency of CD8+ T cells is lower than that induced by VvgB(498-505). Nevertheless, the protection level was comparable when mice were systemically and mucosally challenged during the acute phase. However, such responses by both groups waned with time and were functionally less effective. Still, our results indicate that the CpG ODN-peptide immunization system holds promise as a means of selectively inducing a CD8+ T-cell response against HSV.

PMID: 12050369, UI: 22045634

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Lancet 2002 Jul 13;360(9327):148
 

Mass vaccination after a smallpox attack might be best, researchers suggest.

Lawrence D

[Medline record in process]
 

PMID: 12126834, UI: 22126468

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Lancet 2002 Jun 29;359(9325):2255
 

WHO takes another step towards polio eradication.

Ashraf H

Publication Types:
 

• News

PMID: 12103294, UI: 22100122

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Lancet 2002 May 4;359(9317):1564-8
 

First 5 years of measles elimination in southern Africa: 1996-2000.

Biellik R, Madema S, Taole A, Kutsulukuta A, Allies E, Eggers R, Ngcobo N, Nxumalo M, Shearley A, Mabuzane E, Kufa E, Okwo-Bele JM

WHO, Harare, Zimbabwe. biellikr@who.co.zw

BACKGROUND: Measles is the leading cause of vaccine-preventable death in Africa. Regional measles elimination is considered feasible using current vaccines and a series of WHO-recommended strategies. We aimed to interrupt transmission of measles, and to use case-based surveillance to show the effect of such interruption. METHODS: In southern Africa from 1996, seven countries with a total population of approximately 70 million and with relatively high routine vaccination coverage implemented measles elimination strategies. In addition to routine measles immunisation at 9 months of age, these included nationwide catch-up campaigns among children aged 9 months to 14 years, then follow-up campaigns every 3-4 years among children aged 9-59 months, and the establishment of case-based measles surveillance with serological diagnostic confirmation. RESULTS: Nearly 24 million children aged 9 months to 14 years were vaccinated, with overall vaccination coverage of 91%. Reported clinical measles cases declined from 60000 in 1996 to 117 laboratory-confirmed measles cases in 2000. Reported measles deaths declined from 166 in 1996 to zero in 2000. No increase in adverse events was noted after the measles vaccination campaign. CONCLUSION: A reduction in measles mortality and morbidity can be achieved in very low-income countries, in countries that split their vaccination campaigns by geographical area or by age-group of the target population, and where initial routine measles vaccination coverage among infants was <90%, even when prevalence of HIV/AIDS was extremely high. Continued high-level national commitment will be crucial to implementation and maintenance of proven strategies in southern Africa.

PMID: 12047966, UI: 22043543

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MMWR Morb Mortal Wkly Rep 2002 Jun 28;51(25):549-52, 563
 

Hepatitis B vaccination--United States, 1982-2002.

This year marks the 20th anniversary of the implementation in the United States of the world's first vaccine against hepatitis B virus (HBV). In addition to acute disease, persons infected with HBV are at risk for chronic HBV infection and severe morbidity and mortality from cirrhosis and hepatocellular carcinoma. Before 1982, an estimated 200,000-300,000 persons in the United States were infected annually with HBV, including approximately 20,000 children. No practical method of pre-exposure prophylaxis for HBV existed, and the only postexposure prophylaxis available was injection with hepatitis B immune globulin (HBIG).

PMID: 12118536, UI: 22113649

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MMWR Morb Mortal Wkly Rep 2002 Jun 21;51(24):521-4
 

Progress toward poliomyelitis eradication--Pakistan and Afghanistan, January 2000-April 2002.

Since 1988, when the World Health Assembly resolved to eradicate poliomyelitis worldwide, the estimated global incidence of polio has decreased 99%. Pakistan began polio eradication activities in 1994 and Afghanistan in 1997. Although polio remains endemic in the two countries, both the incidence and the geographic distribution of poliovirus have been reduced substantially. This report summarizes progress toward eradicating polio in Pakistan and Afghanistan during January 2000-April 2002. Both countries aim to stop transmission of poliovirus by the end of 2002; however, the unstable security situation in the region might threaten this success.

PMID: 12088141, UI: 22082672

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Science 2002 Jul 19;297(5580):345-7
 

PARASITOLOGY: Enhanced: Malaria--from Infants to Genomics to Vaccines.

Long CA, Hoffman SL

[Medline record in process]
 

Tropical protozoan parasites are the scourge of the developing world, causing devastating diseases, such as malaria, Chagas' disease, and leishmaniasis. These diseases not only are a huge cause of human misery but also are holding back the economic progress of many developing countries. A pair of Perspectives--by Hol and Gelb, and by Long and Hoffman--report the proceedings of two recent Keystone meetings that examined progress in developing new drugs and vaccines to combat these terrible diseases.

PMID: 12130768, UI: 22127093

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Science 2002 Jul 19;297(5580):319-21
 

FOOT-AND-MOUTH DISEASE: Report Urges U.K. to Vaccinate Herds.

Stone R

[Medline record in process]
 

LONDON--Britain's top scientific body has urged the government to abandon its long-standing practice of relying solely on slaughtering animals to combat future outbreaks of foot-and-mouth disease. Instead, in a report released 16 July, a Royal Society panel has concluded that vaccination and improved data collection should result in better control and fewer dead animals.

PMID: 12130760, UI: 22127085

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Vaccine 2002 Jul 26;20(23-24):3034-41
 

The effect of vaccination with a Salmonella Enteritidis aroA mutant on early cellular responses in caecal lamina propria of newly-hatched chickens.

Van Immerseel F, De Buck J, De Smet I, Mast J, Haesebrouck F, Ducatelle R

Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820, Merelbeke, Belgium

[Medline record in process]
 

When newly hatched chicks are inoculated with a Salmonella strain, they induce a rapid onset of resistance to intestinal colonization by other Salmonella strains. The exact mechanism of this early colonization-inhibition is not known. To study host-related contributions to this phenomenon, the kinetics of immune cell infiltration in the caecal wall was analyzed during the first 10 days after vaccination of newly hatched chickens with a Salmonella enterica serovar Enteritidis aroA mutant, and infection 1 day later with a virulent S. enterica serovar Enteritidis strain. These data were correlated with bacterial colonization and clearance of the Salmonella Enteritidis challenge strain. Bacteriological data showed that vaccinated animals had a much lower number of challenge bacteria in their organs and caecal contents the first days post-challenge, relative to unvaccinated animals. Immunohistochemical analysis of the caecal lamina propria revealed that heterophils started infiltrating the caecal lamina propria from 12h post-vaccination. Macrophages and T-lymphocytes started infiltrating from 20h and B-lymphocytes from 24h post-vaccination. These data imply that immune cells already colonized the caecal wall at the time of challenge in vaccinated animals. The presence and activity of these cells in the caecal wall shortly after administration of a Salmonella Enteritidis aroA mutant might contribute to the inhibition of colonization of a virulent Salmonella strain, subsequently administered.

PMID: 12126917, UI: 22127375

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Vaccine 2002 Jul 26;20(23-24):3005-13
 

Influence of maternal antibodies on efficacy of a subunit vaccine: transmission of classical swine fever virus between pigs vaccinated at 2 weeks of age.

Klinkenberg D, Moormann RJ, de Smit AJ, Bouma A, de Jong MC

Quantitative Veterinary Epidemiology, Institute for Animal Science and Health, P.O. Box 65, 8200 AB, Lelystad, The Netherlands

[Medline record in process]
 

This study shows the effectiveness of vaccination with an E2 subunit vaccine against classical swine fever (CSF) in 2-week-old piglets. Half of the piglets were carrying maternally derived antibodies (MDAs) at the time of vaccination. Three and 6 months later, antibody levels were compared between the two treatments. Moreover, reduction of virus transmission was investigated at 3 and 6 months by doing transmission experiments. The vaccine was found to be capable of reducing virus transmission significantly at both time intervals. Maternal immunity reduced vaccination-induced antibody levels after 3 and 6 months and possibly led to a less effective protection against virus transmission after 6 months.

PMID: 12126914, UI: 22127372

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Vaccine 2002 Jul 26;20(23-24):2972-80
 

Nasal vaccination induces the ability to eliminate Candida colonization without influencing the pre-existing antigen-specific IgE Abs: a possibility for the control of Candida-related atopic dermatitis.

Suenobu N, Kweon MN, Kiyono H

Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, 565-0871, Osaka, Japan

[Medline record in process]
 

In some cases of atopic dermatitis (AD), a possible pathological contribution to disease development by Candida albicans (C. albicans) has been suggested. AD patients with severe symptoms showing positive capsulated hydrolic carrier polymer radioallergosorbent test (CAP-RAST) against C. albicans demonstrated significantly higher levels of serum IgE Abs than did AD patients with mild symptoms. Based on the clinical facts, we have postulated that elimination of C. albicans by mucosal vaccination may lead to the restoration of severe symptoms in AD patients. For this purpose, we have developed an allergic murine model. Mice which were systemically challenged with C. albicans-associated antigen, manganese superoxide dismutase (MnSOD) or secreted aspartic proteases 2 (SAP2), together with alum, exhibited hyper IgE Abs. Systemically primed mice were then immunized with MnSOD or SAP2 plus cholera toxin (CT) as mucosal adjuvant through the nasal route. Interestingly, nasally immunized mice showed increased levels of Candida Ag-specific IgA Ab in fecal and nasal washes as well as in saliva samples but unchanged levels in Ag-specific IgE responses. Consistent with the Ab levels, high numbers of Candida Ag-specific IgA Ab-forming cells were induced in mononuclear cells isolated from intestinal lamina propria, nasal passages and salivary glands of nasally vaccinated mice with Ag plus CT. Furthermore, nasal immunization using MnSOD or SAP2 together with CT resulted in the elimination of colonized C. albicans from the intestinal tract. These results also suggest a potential role of mucosal vaccination in the control of C. albicans in patients with allergic diseases, including AD, although more research is needed to establish this therapeutic approach for mucosal vaccination.

PMID: 12126910, UI: 22127368

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Vaccine 2002 Jul 26;20(23-24):2950-6
 

Early phase II trial of human rotavirus vaccine candidate RV3.

Barnes GL, Lund JS, Mitchell SV, De Bruyn L, Piggford L, Smith AL, Furmedge J, Masendycz PJ, Bugg HC, Bogdanovic-Sakran N, Carlin JB, Bishop RF

Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Vic. 3052, Melbourne, Australia

[Medline record in process]
 

A naturally attenuated, human neonatal strain, rotavirus vaccine candidate RV3, was tested in a limited phase II randomized double-blind controlled trial. Doses of 1ml, containing placebo or 6.5x10(5) fluorescent cell forming units (fcfu) of virus in AGMK cells, were given at 3, 5 and 7 months of age. Limited replication in the small intestine is implied by the lack of virus excretion, and by the occurrence of an immune response in only 46% of the infants. However, those who developed an immune response were partially protected against rotavirus disease during the subsequent winter epidemic (protective efficacy 54%), supporting observations of protection induced by natural infection by this strain. Protection appeared to be heterotypic. Further trials are warranted, employing strategies to increase immunogenicity of this human rotavirus candidate vaccine.

PMID: 12126907, UI: 22127365

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Vaccine 2002 Jul 26;20(23-24):2942-9
 

A comparison of safety, tolerability and immunogenicity of Oka/Merck varicella vaccine and VARILRIX in healthy children.

Lau YL, Vessey SJ, Chan IS, Lee TL, Huang LM, Lee CY, Lin TY, Lee BW, Kwan K, Kasim SM, Chan CY, Kaplan KM, Distefano DJ, Harmon AL, Golie A, Hartzel J, Xu J, Li S, Matthews H, Sadoff JC, Shaw A

Queen Mary Hospital, Pokfulum, Hong Kong, PR China

[Medline record in process]
 

This study compared safety, tolerability, and immunogenicity of the Oka/Merck varicella vaccine and VARILRIX [Oka-RIT strain SmithKline Beecham Biologicals] in healthy children 12-24 months of age. Subjects were randomized in this double blind study to receive either a single dose of Oka/Merck varicella vaccine, ( approximately 50,000 plaque forming units (PFU), Group A or approximately 16,000PFU, Group B) or 1 dose of VARILRIX, ( approximately 40,000PFU/dose, Group C). Safety profiles in each treatment group were similar. The proportions of subjects achieving a 6-week postvaccination titer>/=5gpELISA units in Groups A, B or C were 97.1, 95.2 and 85.6%, respectively.

PMID: 12126906, UI: 22127364

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Vaccine 2002 Jul 26;20(23-24):2928-32
 

Long-term pertussis-specific immune responses to a combined diphtheria, tetanus, tricomponent acellular pertussis and hepatitis B vaccine in pre-term infants.

Esposito S, Faldella G, Giammanco A, Bosis S, Friscia O, Clerici M, Principi N

Pediatric Department I, University of Milan, Via Commenda 9, 20122, Milan, Italy

[Medline record in process]
 

Immunoglobulin G (IgG) antibody titres against pertussis antigens, Bordetella pertussis-specific proliferation and cytokine production by peripheral blood mononuclear cells (PBMCs) were evaluated at the age of 5-6 years in 13 children who had been pre-term infants with a gestational age (GA) of </=31 weeks, 10 who had been pre-term infants with a GA of 32-37 weeks, and 15 who had been term infants with a GA of 38-42 weeks. All of the infants had been immunised with a combined diphtheria, tetanus, tricomponent acellular pertussis and hepatitis B vaccine (DTaP-HBV) at 3, 5, and 11 months of post-natal age. Our results show that the long-term immune responses induced by primary pertussis vaccination in the pre-term infants (especially those with a GA of </=31 weeks) were qualitatively and quantitatively lower than those observed in the term infants. In order to maintain an adequate pertussis-specific immune response, in term children a booster at 5-6 years of age may be suggested, whereas in pre-term an earlier booster should be useful.

PMID: 12126904, UI: 22127362

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Vaccine 2002 Jul 26;20(23-24):2921-7
 

Comparison of the efficacy of early versus late viral proteins in vaccination against SIV.

Stittelaar KJ, Gruters RA, Schutten M, van Baalen CA, van Amerongen G, Cranage M, Liljestrom P, Sutter G, Osterhaus AD

Department of Virology, Erasmus Medical Centre Rotterdam, Dr Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands

[Medline record in process]
 

The immune response against early regulatory proteins of simian- and human immunodeficiency virus (SIV, HIV) has been associated with a milder course of infection. Here, we directly compared vaccination with Tat/Rev versus Pol/Gag. Challenge infection with SIVmac32H (pJ5) suggested that vaccination with Tat/Rev induced cellular immune responses that enabled cynomolgus macaques to more efficiently control SIV replication than the vaccine-induced immune responses against Pol/Gag. Vaccination with Tat/Rev resulted in reduced plasma SIV loads compared with control (P=0.058) or Pol/Gag-vaccinated (P=0.089) animals, with undetectable plasma viral loads in two of the four Tat/Rev-vaccinated animals. Therefore, the results warrant further investigation of the early regulatory proteins and their potential for vaccination against HIV.

PMID: 12126903, UI: 22127361

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Vaccine 2002 Jul 26;20(23-24):2913-20
 

Recombinant Lactobacillus johnsonii as a mucosal vaccine delivery vehicle.

Scheppler L, Vogel M, Zuercher AW, Zuercher M, Germond JE, Miescher SM, Stadler BM

Institute of Immunology and Allergology, Inselspital, 3010, Bern, Switzerland

[Medline record in process]
 

Lactobacilli are considered to be safe organisms making them attractive as vehicles for oral vaccination. We report that Lactobacillus johnsonii (Lj) partially survived simulated gastric conditions in vitro, suggesting that it could be used as an oral vaccine delivery vehicle. In order to test this approach, we used the cell wall anchored proteinase PrtB, isolated from Lactobacillus delbrueckii subsp. bulgaricus as a model antigen. Using a new vector system, we demonstrated expression of both proteinase PrtB alone and a mimotope peptide derived from tetanus toxin integrated in the sequence of proteinase PrtB (TTmim-PrtB fusion protein) on the surface of Lj. Oral immunisation of mice with recombinant Lj, expressing the TTmim-PrtB fusion protein induced a systemic IgG response against Lj and recombinantly expressed proteinase PrtB but no antibody response against the tetanus toxin mimotope suggesting that the mimotope was not sufficiently immunogenic to induce an immune response. Interestingly, a proteinase PrtB specific fecal IgA response was also induced, indicating that the proteinase PrtB fusion protein expressed as a cell surface protein on Lj can induce both systemic and local mucosal immune responses.

PMID: 12126902, UI: 22127360

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Vaccine 2002 Jul 26;20(23-24):2906-12
 

Enteric administration of a live attenuated measles vaccine does not induce protective immunity in a macaque model.

Stittelaar KJ, de Swart RL, Vos HW, van Amerongen G, Agafonov AP, Nechaeva EA, Osterhaus AD

Institute of Virology, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands

[Medline record in process]
 

To test the option of oral vaccination with a live attenuated measles vaccine (LAV), we have evaluated the potential of an orally administered enteric-coated tablet containing a candidate LAV (strain Leningrad-16, MV-L16). To this end three groups of two cynomolgus macaques each were vaccinated via different routes with 10(3.8) TCID(50) MV-L16 vaccine: intramuscularly (i.m.), intraintestinally (i.i.) upon laparotomy and via enteric-coated tablets. Upon vaccination, MV-L16 could only be isolated from one of the i.m.-vaccinated monkeys and not from any of the other five. Both the i.m.-infected monkeys and one of the i.i.-infected monkeys developed a MV-specific serum antibody response. Also, MV-specific CD8(+) IFNgamma-producing T cells could be demonstrated in all three monkeys that had seroconverted. Upon challenge with wild-type MV 1 year after vaccination, only these three monkeys proved to be protected. These data do not support the viability of the concept of oral vaccination with LAVs.

PMID: 12126901, UI: 22127359

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Vaccine 2002 Jul 26;20(23-24):2887-98
 

Enhanced immunogenicity of BCG vaccine by using a viral-based GM-CSF transgene adjuvant formulation.

Wang J, Zganiacz A, Xing Z

Department of Pathology and Molecular Medicine, and Division of Infectious Diseases, Health Science Center, Rm. 4H19, Centre for Gene Therapeutics, McMaster University, 1200 Main Street West, Ont., L8N 3Z5, Hamilton, Canada

[Medline record in process]
 

The failure of current BCG vaccine in controlling the global tuberculosis (TB) epidemic highlights an urgent need for improved TB vaccine formulations. In this study, we have investigated the effect of a novel adenoviral granulocyte macrophage-colony stimulating factor (GM-CSF) transgene-based adjuvant formulation (AdGM-CSF) on BCG vaccination in a mouse strain that is genetically weak responders to BCG vaccine. BALB/c mice were immunized subcutaneously (s.c.) with PBS, BCG, or BCG plus AdGM-CSF or control vector Addl70-3, the immunogenicity of BCG vaccine was evaluated by type 1 IFN-gamma production from lymphocytes of various lymphoid tissues upon mycobacterial antigen stimulation ex vivo. While mycobacterial antigen-specific IFN-gamma production was slightly enhanced by co-immunization BCG with Addl70-3 as compared to BCG immunization alone, a marked increase both in the magnitude and longevity of anti-mycobacterial type 1 immunity was observed in the local draining lymph nodes and spleens by immunization with AdGM-CSF-adjuvanted BCG. Furthermore, there was a significant increase in the number of mycobacterial antigen-specific IFN-gamma releasing CD4 T cells in mice immunized with AdGM-CSF-adjuvanted BCG vaccine. Consistent with these enhanced T-cell immunity and memory responses, AdGM-CSF-adjuvanted BCG vaccine significantly improved immune protection against secondary mycobacterial challenge. Our results suggest that GM-CSF transgene-based adjuvant formulation is an effective way to improve the immunogenicity of BCG vaccine.

PMID: 12126899, UI: 22127357

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Vaccine 2002 Jul 26;20(23-24):2873-7
 

Pig chromosome aberrations after vaccination against classical swine fever in field trials.

Genghini R, Tiranti I, Wittouck P

Genetica, Departamento de Produccion Animal, Facultad de Agronomia y Veterinaria, Universidad Nacional de Rio Cuarto, 5800, Rio Cuarto, Argentina

[Medline record in process]
 

Chromosomal aberrations were observed after vaccination against classical swine fever (CSF) in a previous study done on experimental pigs. To determine if the same effect occurs in farm animals, field trials were done with immunized pigs. The cytogenetic analysis was made from lymphocyte cultures of pigs sampled in three farms of Rio Cuarto region on six different periods: one, pre-vaccination (control) and in five post-vaccination (days 3, 7, 10, 15 and 22). Vaccine inoculation induced significant increase of cell frequency with chromosomal aberrations from days 3 to 10, when maximal frequencies of 6.78, 10.36 and 7.21% were observed in farms A, B and C, respectively. Afterwards, a decrease was recorded, reaching values not significantly different from controls. Mean frequencies of cells with chromosomal aberrations were 2.8+/-0.3, 5.9+/-0.4, 3.1+/-0.3%, for A, B and C farms, respectively. Cytogenetic effect was clastogenic, being chromosome breaks the first type of alteration to increase from the day 3 post-vaccination onwards, followed by chromatid exchanges and cells with multiple abnormalities. Chromosome pulverization was the last type to show increment, reaching a top value on day 10, after that it started to diminish gradually. There was no difference in the frequency of polyploid cells among sampling dates meaning that this type of alteration would not be induced by vaccination. Results of this field study confirm the mutagenic capacity of live virus vaccines against CSF and indicate that the evolution of chromosome alterations on the five evaluated post-vaccination periods was similar at different environments.

PMID: 12126897, UI: 22127355

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Vaccine 2002 Jul 26;20(23-24):2866-72
 

Protection against oronasal challenge with virulent feline leukaemia virus lasts for at least 12 months following a primary course of immunisation with Leukocell 2 vaccine.

Harbour DA, Gunn-Moore DA, Gruffydd-Jones TJ, Caney SM, Bradshaw J, Jarrett O, Wiseman A

Department of Clinical Veterinary Science, Division of Molecular and Cellular Biology, University of Bristol, Langford House, Langford, BS40 5DU, Bristol, UK

[Medline record in process]
 

The duration of immunity provided by a feline leukemia virus (FeLV) vaccine, Leukocell 2, was determined. Kittens were vaccinated when 9 and 12 weeks of age and were challenged 12 months later with FeLV-A/Glasgow-1. An oronasal challenge protocol without corticosteroid enhancement was developed in order to induce a persistent viraemia in a high proportion of adult cats. Fourteen of 18 (80%) of the vaccinated cats challenged in this way remained non-viraemic while 9/15 (60%) of age-matched controls became persistently infected, a preventable fraction of 63%. This difference was statistically significant (P=0.038). For comparison, 10 of 12 (83%) 15-17-week-old kittens challenged in the same way became persistently infected, confirming the relative resistance of adult animals to FeLV. Tests for virus neutralising and anti-feline oncornavirus-associated cell membrane antigen (FOCMA) antibodies suggested that the former were more important than the latter in protection. Thus, Leukocell 2 protected a significant proportion of cats from FeLV challenge 1 year after primary vaccination as kittens.

PMID: 12126896, UI: 22127354

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Vaccine 2002 Jul 26;20(23-24):2857-65
 

Adjuvant effect of multi-CpG motifs on an HIV-1 DNA vaccine.

Kojima Y, Xin KQ, Ooki T, Hamajima K, Oikawa T, Shinoda K, Ozaki T, Hoshino Y, Jounai N, Nakazawa M, Klinman D, Okuda K

Department of Bacteriology, University School of Medicine, Yokohama City, 236-0004, Yokohama, Japan

[Medline record in process]
 

Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs trigger an immune response characterized by the activation of B cells, NK cells and monocytes/macrophages. Based on evidence that the immunogenicity of DNA vaccines can be augmented by the addition of CpG motifs, 5-20 additional CpG motifs were cloned into a pUC-derived plasmid. Treating bone-marrow derived dendritic cells (BM-DCs) with CpG-enriched plasmids in vitro boosted their expressions of MHC class II molecules, the CD40 and CD86 activation markers. Co-administering the CpG-enriched plasmids with a DNA vaccine encoding the envelope glycoprotein of HIV to BALB/c mice significantly increased HIV-specific cell mediated and humoral immunity. A significant boost was observed when the CpG plasmid was administered either 2 or 4 days after DNA vaccination. Plasmids containing 20 CpG copies were the most effective immune enhancers both in vitro and in vivo. These results suggest that plasmids containing multiple CpG motifs may improve the immunogenicity of DNA vaccines.

PMID: 12126895, UI: 22127353

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Vaccine 2002 Jul 26;20(23-24):2851-2856
 

Anticapsular polysaccharide meningococcal antibodies in Israeli military recruits: immune status and the effect of simultaneous administration of immune globulin on the response to polysaccharide vaccine.

Shapira-Nahor O, Grotto I, Adler A, Mandel Y, Ashkenazi I, Block C

Department of Clinical Microbiology and Infectious Diseases, Hadassah-University Hospital, P.O. Box 12000, 91120, Jerusalem, Israel

[Record supplied by publisher]
 

The effect of the administration of immune globulin (Ig), given during summer months to prevent hepatitis A, on the immune response to a simultaneously administered quadrivalent meningococcal polysaccharide vaccine (QMPV) was studied in Israeli military recruits. Data were obtained for the first time regarding the immune status of an Israeli population. Anticapsular polysaccharide antibodies were determined using a standardized ELISA assay before, 2 weeks and 3 months after QMPV immunization with or without Ig in two groups of recruits chosen to span the date determining seasonal administration or non-administration of Ig. Pre-vaccination antibody concentrations were >/=2&mgr;g/ml in 98.4 and 38.9% of subjects against serogroups A and C meningococci, respectively. These levels are consistent with the extremely low incidence of disease due to serogroup A in Israel, and with the previously documented occurrence of serogroup C disease in servicemen and women. Co-administration of Ig was associated with some reduction in antibody concentrations 3 months after vaccination, especially against serogroup A meningococci (P<0.05), but not to an extent likely to be of clinical significance.

PMID: 12126894

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Vaccine 2002 Jul 26;20(23-24):2845-7
 

On the 2002 measles vaccination furore in the UK.

Spier RE

School of Biomedical and Life Sciences, University of Surrey, Surrey GU2 7XH, Guildford, UK

[Medline record in process]
 

PMID: 12126892, UI: 22127350

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Wkly Epidemiol Rec 2002 Jun 7;77(23):191-5
 

Adoption of Global Agenda on Influenza--Part II.

PMID: 12073536, UI: 22069386

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Wkly Epidemiol Rec 2002 Jun 7;77(23):185-90
 

Progress towards poliomyelitis eradication.

PMID: 12073535, UI: 22069385

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