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J Immunol 2002 Nov 15;169(10):6030-5
 

DNA vaccination with heat shock protein 60 inhibits cyclophosphamide-accelerated diabetes.

Quintana FJ, Carmi P, Cohen IR

Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.

[Medline record in process]
 

Nonobese diabetic (NOD) mice spontaneously develop diabetes as a consequence of an autoimmune process that can be inhibited by immunotherapy with the 60-kDa heat shock protein (hsp60), with its mycobacterial counterpart 65-kDa (hsp65), or with other Ags such as insulin and glutamic acid decarboxylase (GAD). Microbial infection and innate signaling via LPS or CpG motifs can also inhibit the spontaneous diabetogenic process. In addition to the spontaneous disease, however, NOD mice can develop a more robust cyclophosphamide-accelerated diabetes (CAD). In this work, we studied the effect on CAD of DNA vaccination with constructs encoding the Ags human hsp60 (phsp60) or mycobacterial hsp65 (phsp65). Vaccination with phsp60 protected NOD mice from CAD. In contrast, vaccination with phsp65, with an empty vector, or with a CpG-positive oligonucleotide was not effective, suggesting that the efficacy of the phsp60 construct might be based on regulatory hsp60 epitopes not shared with its mycobacterial counterpart, hsp65. Vaccination with phsp60 modulated the T cell responses to hsp60 and also to the GAD and insulin autoantigens; T cell proliferative responses were significantly reduced, and the pattern of cytokine secretion to hsp60, GAD, and insulin showed an increase in IL-10 and IL-5 secretion and a decrease in IFN-gamma secretion, compatible with a shift from a Th1-like toward a Th2-like autoimmune response. Our results extend the role of specific hsp60 immunomodulation in the control of beta cell autoimmunity and demonstrate that immunoregulatory networks activated by specific phsp60 vaccination can spread to other Ags targeted during the progression of diabetes, like insulin and GAD.

PMID: 12421990, UI: 22309162

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J Immunol 2002 Nov 15;169(10):5771-5779
 

Induction of HIV-1-Specific Immunity After Vaccination with Apoptotic HIV-1/Murine Leukemia Virus-Infected Cells.

Spetz AL, Sorensen AS, Walther-Jallow L, Wahren B, Andersson J, Holmgren L, Hinkula J

Department of Medicine, Center for Infectious Medicine, Huddinge University Hospital, and Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden. Swedish Institute for Infectious Disease Control, Stockholm, Sweden. Cancer Center, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden. Department of Health and Society, Malmo University, Malmo, Sweden.

[Record supplied by publisher]
 

Ag-presenting dendritic cells present viral Ags to T cells after uptake of apoptotic bodies derived from virus-infected cells in vitro. However, it is unclear whether apoptotic virus-infected cells are capable of generating immunity in vivo. In this study, we show that inoculation of mice with apoptotic HIV-1/murine leukemia virus (MuLV)-infected cells induces HIV-1-specific immunity. Immunization with apoptotic HIV-1/MuLV-infected syngeneic splenocytes resulted in strong Nef-specific CD8(+) T cell proliferation and p24-induced CD4(+) and CD8(+) T cell proliferation as well as IFN-gamma production. In addition, systemic IgG and IgA as well as mucosa-associated IgA responses were generated. Moreover, mice vaccinated with apoptotic HIV-1/MuLV cells were protected against challenge with live HIV-1/MuLV-infected cells, whereas mice vaccinated with apoptotic noninfected or MuLV-infected splenocytes remained susceptible to HIV-1/MuLV. These data show that i.p. immunization with apoptotic HIV-1-infected cells induces high levels of HIV-1-specific systemic immunity, primes for mucosal immunity, and induces protection against challenge with live HIV-1-infected cells in mice. These findings may have implications for the development of therapeutic and prophylactic HIV-1 vaccines.

PMID: 12421957

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J Virol 2002 Dec 1;76(23):12335-12343
 

Binding of Norwalk Virus-Like Particles to ABH Histo-Blood Group Antigens Is Blocked by Antisera from Infected Human Volunteers or Experimentally Vaccinated Mice.

Harrington PR, Lindesmith L, Yount B, Moe CL, Baric RS

Department of Microbiology and Immunology, School of Medicine. Program in Infectious Diseases, Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7435. Department of International Health, Rollins School of Public Health, Emory University, Atlanta, Georgia 30322.

[Record supplied by publisher]
 

Attachment of Norwalk (NV), Snow Mountain (SMV), and Hawaii (HV) virus-like particles (VLPs) to specific ABH histo-blood group antigens was investigated by using human saliva and synthetic biotinylated carbohydrates. The three distinct Norwalk-like viruses (NLVs) have various capacities for binding ABH histo-blood group antigens, suggesting that different mechanisms for NLV attachment likely exist. Importantly, antisera from NV-infected human volunteers, as well as from mice inoculated with packaged Venezuelan equine encephalitis virus replicons expressing NV VLPs, blocked the ability of NV VLPs to bind synthetic H type 1, Le(b), and H type 3, suggesting a potential mechanism for antibody-mediated neutralization of NV.

PMID: 12414974

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J Virol 2002 Dec;76(23):11911-9
 

Neonates Mount Robust and Protective Adult-Like CD8(+)-T-Cell Responses to DNA Vaccines.

Zhang J, Silvestri N, Whitton JL, Hassett DE

The Scripps Research Institute, La Jolla, California 92037.

[Medline record in process]
 

Neonates are thought to mount less vigorous adaptive immune responses than adults to antigens and infectious agents. This concept has led to a delay in the administration of many currently available vaccines until late infancy or early childhood. It has recently been shown that vaccines composed of plasmid DNA can induce both humoral and cell-mediated antimicrobial immunity when administered within hours of birth. In most of these studies, immune responses were measured weeks or months after the initial vaccination, and it is therefore questionable whether the observed responses were actually the result of priming of splenocytes within the neonatal period. Here we show that DNA vaccination at birth results in the rapid induction of antigen-specific CD8(+) T cells within neonatal life. Analyses of T-cell effector functions critical for the resolution of many viral infections revealed that neonatal and adult CD8(+) T cells produce similar arrays of cytokines. Furthermore, the avidities of neonatal and adult CD8(+) T cells for peptide and the rapidity with which they upregulate cytokine production after recall encounters with antigen are similar. Protective immunity against the arenavirus lymphocytic choriomeningitis virus, which is mediated by CD8(+) cytotoxic T cells, is also rapidly acquired within the neonatal period. Collectively these data imply that, at least in the case of CD8(+) T cells, neonates are not as immunodeficient as previously supposed and that DNA vaccines may be an effective and safe means of providing critical cell-mediated antiviral immunity extremely early in life.

PMID: 12414933, UI: 22302301

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J Virol 2002 Dec 1;76(23):11837-11844
 

Comparison of Molecular and Biological Characteristics of a Modified Live Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Vaccine (Ingelvac PRRS MLV), the Parent Strain of the Vaccine (ATCC VR2332), ATCC VR2385, and Two Recent Field Isolates of PRRSV.

Opriessnig T, Halbur PG, Yoon KJ, Pogranichniy RM, Harmon KM, Evans R, Key KF, Pallares FJ, Thomas P, Meng XJ

Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa 50011. Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061. Departamento de Anatomia y Anatomia Patologica Comparada, Facultad de Veterinaria, Universidad de Murcia, Murcia, Spain.

[Record supplied by publisher]
 

The objectives of this study were to compare the molecular and biological characteristics of recent porcine reproductive and respiratory syndrome virus (PRRSV) field isolates to those of a modified live virus (MLV) PRRS vaccine and its parent strain. One hundred seventeen, 4-week-old pigs were randomly assigned to six groups. Group 1 (n = 20) served as sham-inoculated negative controls, group 2 (n = 19) was inoculated with Ingelvac PRRS MLV vaccine, group 3 (n = 20) was inoculated with the parent strain of the vaccine (ATCC VR2332), group 4 (n = 19) was inoculated with vaccine-like PRRSV field isolate 98-38803, group 5 (n = 19) was inoculated with PRRSV field isolate 98-37120, and group 6 (n = 20) was inoculated with known high-virulence PRRSV isolate ATCC VR2385. The levels of severity of gross lung lesions (0 to 100%) among the groups were significantly different at both 10 (P < 0.0001) and 28 days postinoculation (p.i.) (P = 0.002). At 10 days p.i., VR2332 (26.5% +/- 4.64%) and VR2385 (36.4% +/- 6.51%) induced gross lesions of significantly greater severity than 98-38803 (0.0% +/- 0.0%), 98-37120 (0.8% +/- 0.42%), Ingelvac PRRS MLV (0.9% +/- 0.46%), and negative controls (2.3% +/- 1.26%). At 28 days p.i., 98-37120 (17.2% +/- 6.51%) induced gross lesions of significantly greater severity than any of the other viruses. Analyses of the microscopic-interstitial-pneumonia-lesion scores (0 to 6) revealed that VR2332 (2.9 +/- 0.23) and VR2385 (3.1 +/- 0.35) induced significantly more severe lesions at 10 days p.i. At 28 days p.i., VR2385 (2.5 +/- 0.27), VR2332 (2.3 +/- 0.21), 98-38803 (2.6 +/- 0.29), and 98-37120 (3.0 +/- 0.41) induced significantly more severe lesions than Ingelvac PRRS MLV (0.7 +/- 0.17) and controls (0.7 +/- 0.15). The molecular analyses and biological characterizations suggest that the vaccine-like isolate 98-38803 (99.5% amino acid homology based on the ORF5 gene) induces microscopic pneumonia lesions similar in type to, but different in severity and time of onset from, those observed with virulent strains VR2385 and the parent strain of the vaccine. Our data strongly suggest that isolate 98-38803 is a derivative of Ingelvac PRRS MLV and that the isolate is pneumovirulent.

PMID: 12414926

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Lancet 2002 Oct 26;360(9342):1307
 

Unclear whether monkey virus in old polio vaccines caused cancer, says IOM.

McCarthy M

[Medline record in process]
 

PMID: 12414212, UI: 22302423

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N Engl J Med 2002 Nov 7;347(19):1477-82
 

A population-based study of measles, mumps, and rubella vaccination and autism.

Madsen KM, Hviid A, Vestergaard M, Schendel D, Wohlfahrt J, Thorsen P, Olsen J, Melbye M

Danish Epidemiology Science Center, Department of Epidemiology and Social Medicine, Arhus, Denmark. kmm@dadlnet.dk

[Medline record in process]
 

BACKGROUND: It has been suggested that vaccination against measles, mumps, and rubella (MMR) is a cause of autism. METHODS: We conducted a retrospective cohort study of all children born in Denmark from January 1991 through December 1998. The cohort was selected on the basis of data from the Danish Civil Registration System, which assigns a unique identification number to every live-born infant and new resident in Denmark. MMR-vaccination status was obtained from the Danish National Board of Health. Information on the children's autism status was obtained from the Danish Psychiatric Central Register, which contains information on all diagnoses received by patients in psychiatric hospitals and outpatient clinics in Denmark. We obtained information on potential confounders from the Danish Medical Birth Registry, the National Hospital Registry, and Statistics Denmark. RESULTS: Of the 537,303 children in the cohort (representing 2,129,864 person-years), 440,655 (82.0 percent) had received the MMR vaccine. We identified 316 children with a diagnosis of autistic disorder and 422 with a diagnosis of other autistic-spectrum disorders. After adjustment for potential confounders, the relative risk of autistic disorder in the group of vaccinated children, as compared with the unvaccinated group, was 0.92 (95 percent confidence interval, 0.68 to 1.24), and the relative risk of another autistic-spectrum disorder was 0.83 (95 percent confidence interval, 0.65 to 1.07). There was no association between the age at the time of vaccination, the time since vaccination, or the date of vaccination and the development of autistic disorder. CONCLUSIONS: This study provides strong evidence against the hypothesis that MMR vaccination causes autism. Copyright 2002 Massachusetts Medical Society

PMID: 12421889, UI: 22309432

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N Engl J Med 2002 Nov 7;347(19):1474-5
 

Suspicions about the safety of vaccines.

Campion EW

[Medline record in process]
 

Publication Types:
 

• Comment

PMID: 12421888, UI: 22309431

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Nat Med 2002 Nov 4;
 

A DNA vaccine against VEGF receptor 2 prevents effective angiogenesis and inhibits tumor growth.

Niethammer AG, Xiang R, Becker JC, Wodrich H, Pertl U, Karsten G, Eliceiri BP, Reisfeld RA

Department of Immunology, Scripps Research Institute, La Jolla, California, USA.

[Record supplied by publisher]
 

Tumor cells are elusive targets for immunotherapy due to their heterogeneity and genetic instability. Here we describe a novel, oral DNA vaccine that targets stable, proliferating endothelial cells in the tumor vasculature rather than tumor cells. Targeting occurs through upregulated vascular-endothelial growth factor receptor 2 (FLK-1) of proliferating endothelial cells in the tumor vasculature. This vaccine effectively protected mice from lethal challenges with melanoma, colon carcinoma and lung carcinoma cells and reduced growth of established metastases in a therapeutic setting. CTL-mediated killing of endothelial cells indicated breaking of peripheral immune tolerance against this self antigen, resulting in markedly reduced dissemination of spontaneous and experimental pulmonary metastases. Angiogenesis in the tumor vasculature was suppressed without impairment of fertility, neuromuscular performance or hematopoiesis, albeit with a slight delay in wound healing. Our strategy circumvents problems in targeting of genetically unstable tumor cells. This approach may provide a new strategy for the rational design of cancer therapies.

PMID: 12415261

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Pediatrics 2002 Nov;110(5):957-63
 

Neurologic disorders after measles-mumps-rubella vaccination.

Makela A, Nuorti JP, Peltola H

Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland. Department of Infectious Disease Epidemiology, National Public Health Institute, Helsinki, Finland.

[Medline record in process]
 

OBJECTIVE: The possibility of adverse neurologic events has fueled much concern about the safety of measles-mumps-rubella (MMR) vaccinations. The available evidence concerning several of the postulated complications is controversial. The aim of this study was to assess whether an association prevails between MMR vaccination and encephalitis, aseptic meningitis, and autism. METHODS: A retrospective study based on linkage of individual MMR vaccination data with a hospital discharge register was conducted among 535 544 1- to 7-year-old children who were vaccinated between November 1982 and June 1986 in Finland. For encephalitis and aseptic meningitis, the numbers of events observed within a 3-month risk interval after vaccination were compared with the expected numbers estimated on the basis of occurrence of encephalitis and aseptic meningitis during the subsequent 3-month intervals. Changes in the overall number of hospitalizations for autism after vaccination throughout the study period were searched for. In addition, hospitalizations because of inflammatory bowel diseases were checked for the children with autism. RESULTS: Of the 535 544 children who were vaccinated, 199 were hospitalized for encephalitis, 161 for aseptic meningitis, and 352 for autistic disorders. In 9 children with encephalitis and 10 with meningitis, the disease developed within 3 months of vaccination, revealing no increased occurrence within this designated risk period. We detected no clustering of hospitalizations for autism after vaccination. None of the autistic children made hospital visits for inflammatory bowel diseases. CONCLUSIONS: We did not identify any association between MMR vaccination and encephalitis, aseptic meningitis, or autism.

PMID: 12415036, UI: 22302855

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Pediatrics 2002 Nov;110(5):929-34
 

Hepatitis B vaccination among adolescents in 3 large health maintenance organizations.

Gonzalez IM, Averhoff FM, Massoudi MS, Yusuf H, DeStefano F, Kramarz P, Maher JE, Mullooly JP, Chun C, Davis RL, Black SB, Shinefield HR

Epidemiology Program Office, National Immunization Program, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.

[Medline record in process]
 

OBJECTIVE: In 1995, the Advisory Committee on Immunization Practices (ACIP) recommended routine hepatitis B (HB) vaccination of all unvaccinated 11- to 12-year-old adolescents. Little is known about the implementation of these recommendations in a managed care setting. The objective of this study was to determine the impact of ACIP recommendations on HB vaccination among adolescents in 3 managed care settings. METHODS: We assessed HB vaccination coverage among adolescents who were enrolled in 3 large health maintenance organizations (HMOs) and who turned 13 years old after the 1995 ACIP recommendations. Children who were 8 to 10 years of age during May 1993 and were continuously enrolled through December 1998 were eligible. We used the HMOs' computerized immunization tracking system to collect HB vaccination dates. The percentage of adolescents who received 3 doses of HB vaccine was determined. RESULTS: In HMOs A, B, and C, coverage levels for 3 doses of HB vaccine were 43.4%, 65.5%, and 25.7%, respectively, among 13-year-olds in 1998 compared with 26.1%, 50.4%, and 5.5% among 13-year-olds in 1996. Between the ages of 11 and 13 years, coverage rates among adolescents aged 13 in 1998 rose more than the coverage among adolescents aged 13 in 1996. The proportion of 13-year-olds in 1998 who received the first dose of HB vaccine by December 1998 was much higher at 89.6%, 65.2%, and 56.6% in HMOs A, B, and C, respectively, compared with the proportion who completed the 3-dose series (43.4%, 65.5%, and 25.7%, respectively). CONCLUSIONS: After the 1995 ACIP recommendations, HB vaccination coverage levels among 13-year-olds increased in each of the HMOs, suggesting adherence with national recommendations. Differences among the 3 HMOs may reflect differences in internal policies. More effective strategies may be needed to achieve the Healthy People 2010 goal of 90% vaccination coverage rates among adolescents.

PMID: 12415032, UI: 22302851

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