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Clin Infect Dis 2003 Feb 15;36(4):468-71
 

Smallpox vaccination and patients with human immunodeficiency virus infection or acquired immunodeficiency syndrome.

Bartlett JG

Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. jb@jhmi.edu

[Medline record in process]
 

Smallpox vaccination strategies are evolving rapidly and have important implications for human immunodeficiency virus (HIV)-infected persons. Cell-mediated immunity is important for controlling both smallpox and vaccinia. For smallpox, the concern is a substantial increase in the associated mortality rate, which is 30% among healthy persons. For smallpox vaccination, the concern is progressive vaccinia, which is usually lethal but relatively uncommon. The risks associated with both smallpox and vaccinia viruses probably correlate with CD4 cell count, and, as a corollary, the best protection against infection with each is presumably immune reconstitution. It appears that all vaccinations will be voluntary, with 2 recommendations: (1) HIV-infected persons will be advised to decline preemptive vaccination, and (2) in the event of a bioterrorism attack involving smallpox, HIV-infected patients with exposures will be advised to receive vaccine.

PMID: 12567305, UI: 22453183

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Clin Infect Dis 2003 Jan 15;36(2):140-8
 

Spectrum of bacille Calmette-Guerin (BCG) infection after intravesical BCG immunotherapy.

Gonzalez OY, Musher DM, Brar I, Furgeson S, Boktour MR, Septimus EJ, Hamill RJ, Graviss EA

Department of Medicine, Infectious Disease Section, Baylor College of Medicine, Houston, TX 77030-3498, USA.

Intravesical instillation of bacille Calmette-Guerin (BCG) effectively treats transitional cell carcinoma of the bladder. Occasionally, BCG infection complicates such treatment. In some patients, infection appears early (within 3 months after instillation) and is characterized by generalized symptoms, with pneumonitis and hepatitis. Late-presentation disease occurs >1 year after the first BCG treatment and usually involves focal infection of the genitourinary tract (the site at which bacteria were introduced) and/or other sites that are typical for reactivation of mycobacterial disease, such as the vertebral spine or the retroperitoneal tissues. Noncaseating granulomas are found in the majority of cases, whether early or late. Most patients respond to treatment with antituberculous drugs; in early-presentation disease, when features of hypersensitivity predominate, glucocorticosteroids are sometimes added. Late localized infection often requires surgical resection.

PMID: 12522745, UI: 22409796

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J Immunol 2003 Feb 15;170(4):1980-6
 

Prevention of spontaneous breast carcinoma by prophylactic vaccination with dendritic/tumor fusion cells.

Xia J, Tanaka Y, Koido S, Liu C, Mukherjee P, Gendler SJ, Gong J

Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115. Boston University School of Medicine, Boston, MA 02118. Mayo Clinic, Scottsdale, AZ 85259. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115.

[Medline record in process]
 

Genetically modified mice with spontaneous development of mammary carcinoma provide a powerful tool to study the efficacy of tumor vaccines, since they mimic breast cancer development in humans. We used a transgenic murine model expressing polyomavirus middle T oncogene and mucin 1 tumor-associated Ag to determine the preventive effect of a dendritic/tumor fusion cell vaccine. The MMT (a transgenic murine model) mice developed mammary carcinoma between the ages of 65-108 days with 100% penetrance. No spontaneous CTL were detected. However, prophylactic vaccination of MMT mice with dendritic/tumor fusion cells induced polyclonal CTL activity against spontaneous mammary carcinoma cells and rendered 57-61% of the mice free of the disease at the end of experiment (180 days). Furthermore, the level of CTL activity was maintained with multiple vaccinations. The antitumor immunity induced by vaccination with dendritic/tumor fusion cells reacted differently to injected tumor cells and autochthonous tumor. Whereas the injected tumor cells were rejected, the autochthonous tumor evaded the attack and was allowed to grow. Collectively these results indicate that prophylactic vaccination with dendritic/tumor fusion cells confers sufficient antitumor immunity to counter the tumorigenesis of potent oncogenic products. The findings in the present study are highly relevant to cancers in humans.

PMID: 12574367, UI: 22462100

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J Immunol 2003 Feb 15;170(4):1806-1813
 

Suppressive DNA Vaccination in Myelin Oligodendrocyte Glycoprotein Peptide-Induced Experimental Autoimmune Encephalomyelitis Involves a T1-Biased Immune Response.

Lobell A, Weissert R, Eltayeb S, De Graaf KL, Wefer J, Storch MK, Lassmann H, Wigzell H, Olsson T

Neuroimmunology Unit, Center for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden. Department of Neurology, University of Tuebingen, Tuebingen, Germany. Neurological Institute, University of Vienna, Vienna, Austria. Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.

[Record supplied by publisher]
 

Vaccination with DNA encoding a myelin basic protein peptide suppresses Lewis rat experimental autoimmune encephalomyelitis (EAE) induced with the same peptide. Additional myelin proteins, such as myelin oligodendrocyte glycoprotein (MOG), may be important in multiple sclerosis. Here we demonstrate that DNA vaccination also suppresses MOG peptide-induced EAE. MOG(91-108) is encephalitogenic in DA rats and MHC-congenic LEW.1AV1 (RT1(av1)) and LEW.1N (RT1(n)) rats. We examined the effects of DNA vaccines encoding MOG(91-108) in tandem, with or without targeting of the hybrid gene product to IgG. In all investigated rat strains DNA vaccination suppressed clinical signs of EAE. There was no requirement for targeting the gene product to IgG, but T1-promoting CpG DNA motifs in the plasmid backbone of the construct were necessary for efficient DNA vaccination, similar to the case in DNA vaccination in myelin basic protein-induced EAE. We failed to detect any effects on ex vivo MOG-peptide-induced IFN-gamma, TNF-alpha, IL-6, IL-4, IL-10, and brain-derived neurotropic factor expression in splenocytes or CNS-derived lymphocytes. In CNS-derived lymphocytes, Fas ligand expression was down-regulated in DNA-vaccinated rats compared with controls. However, MOG-specific IgG2b responses were enhanced after DNA vaccination. The enhanced IgG2b responses together with the requirement for CpG DNA motifs in the vaccine suggest a protective mechanism involving induction of a T1-biased immune response.

PMID: 12574345

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J Immunol 2003 Feb 15;170(4):1641-1648
 

Targeting Apoptotic Tumor Cells to FcgammaR Provides Efficient and Versatile Vaccination Against Tumors by Dendritic Cells.

Akiyama K, Ebihara S, Yada A, Matsumura K, Aiba S, Nukiwa T, Takai T

Department of Experimental Immunology and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, and Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan. Department of Dermatology, Tohoku University School of Medicine, Sendai, Japan.

[Record supplied by publisher]
 

Dendritic cells (DCs) loaded with tumor-associated Ags (TAAs) act as potent adjuvant that initiates antitumor immune responses in vivo. However, TAA-based DC vaccination requires prior identification of TAAs. Apoptotic tumor cells (ATCs) can be an excellent source for DC loading because their potential uncharacterized Ags would be efficiently presented to T cells without any prior characterization and isolation of these Ags. However, ATCs alone are considered to be inefficient for activating antitumor immunity, possibly because of their inability to induce DC maturation. In this study, the aim was to enhance antitumor immune response by taking advantage of ATCs that have been opsonized with IgG (ATC-immune complexes, ATC-ICs) so as to target them to FcR for IgG (FcgammaRs) on DCs. It was found that when compared with ATCs, ATC-ICs were efficiently internalized by DCs via FcgammaRs, and this process induced maturation of DCs, which was more efficient than that of ATCs. Importantly, ATC-IC loading was shown to be more efficient than ATCs alone in its capacity for inducing antitumor immunity in vivo, in terms of cytotoxic T cell induction and tumor rejection. These results show that using ATC-ICs may overcome the limitations and may enhance the immune response of current ATC-based DC vaccination therapy.

PMID: 12574326

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Lancet 2003 Feb 1;361(9355):395-6
 

Effectiveness of vaccination for Haemophilus influenzae type b.

Garner D, Weston V

Department of Microbiology and Public Health Laboratory, Queens Medical Centre, University Hospital, NG7 2UH, Nottingham, UK

[Medline record in process]
 

PMID: 12573380, UI: 22462344

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Lancet 2003 Feb 1;361(9355):360-1
 

Conjugate Hib vaccines.

Steinhoff M, Goldblatt D

Johns Hopkins University School of Medicine, School of Hygiene, 21205, Baltimore, MD, USA

[Medline record in process]
 

PMID: 12573368, UI: 22462332

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N Engl J Med 2003 Jan 30;348(5):463-6
 

Preventing the return of smallpox.

Breman JG, Arita I, Fenner F

Fogarty International Center, Bethesda, Md 20892-6705, USA. jbreman@nih.gov

PMID: 12556549, UI: 22444742

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N Engl J Med 2003 Jan 30;348(5):426-32
 

The public and the smallpox threat.

Blendon RJ, DesRoches CM, Benson JM, Herrmann MJ, Taylor-Clark K, Weldon KJ

Department of Health Policy and Management, Harvard School of Public Health, Boston 02115, USA.

BACKGROUND: The potential for a bioterrorist attack involving smallpox has led to a debate about what national precautions should be taken. What is unclear is the public's knowledge of smallpox and views about precautions. METHODS: We conducted a national survey of 1006 adults selected by means of random-digit dialing. Respondents were asked about their knowledge of and beliefs about the smallpox virus and the vaccine, their possible reactions to a bioterrorist attack involving smallpox, and a number of proposed state emergency powers. RESULTS: The majority of the respondents have a number of beliefs about smallpox and smallpox vaccination that are false. The majority believe that there is an effective treatment for smallpox, that there have been cases of smallpox in the past five years, and that there is not enough smallpox vaccine to vaccinate everyone in the United States. Thirty percent believe that vaccination earlier in their lives would protect them from the disease. The majority of respondents said they wanted to be vaccinated; however, only 21 percent would want to be vaccinated if physicians declined vaccination. There was strong support among the respondents for several proposed state emergency powers. CONCLUSIONS: Our results suggest the need for public education about smallpox. These data also point to the importance of a discussion in the medical community about the advisability of vaccination of individual physicians at this time. Copyright 2003 Massachusetts Medical Society

PMID: 12496352, UI: 22444730

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