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J Virol 2003 Mar;77(6):3655-68
 

Yellow fever virus/dengue-2 virus and yellow fever virus/dengue-4 virus chimeras: biological characterization, immunogenicity, and protection against dengue encephalitis in the mouse model.

Chambers TJ, Liang Y, Droll DA, Schlesinger JJ, Davidson AD, Wright PJ, Jiang X

Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine, St. Louis, Missouri 63104, USA. chambetj@slu.edu

Two yellow fever virus (YFV)/dengue virus chimeras which encode the prM and E proteins of either dengue virus serotype 2 (dengue-2 virus) or dengue-4 virus within the genome of the YFV 17D strain (YF5.2iv infectious clone) were constructed and characterized for their properties in cell culture and as experimental vaccines in mice. The prM and E proteins appeared to be properly processed and glycosylated, and in plaque reduction neutralization tests and other assays of antigenic specificity, the E proteins exhibited profiles which resembled those of the homologous dengue virus serotypes. Both chimeric viruses replicated in cell lines of vertebrate and mosquito origin to levels comparable to those of homologous dengue viruses but less efficiently than the YF5.2iv parent. YFV/dengue-4 virus, but not YFV/dengue-2 virus, was neurovirulent for 3-week-old mice by intracerebral inoculation; however, both viruses were attenuated when administered by the intraperitoneal route in mice of that age. Single-dose inoculation of either chimeric virus at a dose of 10(5) PFU by the intraperitoneal route induced detectable levels of neutralizing antibodies against the homologous dengue virus strains. Mice which had been immunized in this manner were fully protected from challenge with homologous neurovirulent dengue viruses by intracerebral inoculation compared to unimmunized mice. Protection was associated with significant increases in geometric mean titers of neutralizing antibody compared to those for unimmunized mice. These data indicate that YFV/dengue virus chimeras elicit antibodies which represent protective memory responses in the mouse model of dengue encephalitis. The levels of neurovirulence and immunogenicity of the chimeric viruses in mice correlate with the degree of adaptation of the dengue virus strain to mice. This study supports ongoing investigations concerning the use of this technology for development of a live attenuated viral vaccine against dengue viruses.

PMID: 12610141, UI: 22497629

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J Virol 2003 Mar;77(6):3615-23
 

Enhancement of mucosal immunization with virus-like particles of simian immunodeficiency virus.

Kang SM, Compans RW

Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

Cholera toxin (CT) is the most potent known mucosal adjuvant, but its toxicity precludes its use in humans. Here, in an attempt to develop safe and effective mucosal adjuvants, we compared immune responses to simian immunodeficiency virus (SIV) virus-like particles (VLPs) after intranasal coimmunization with RANTES, CpG oligodeoxynucleotides (ODN), or CT. Antibody analysis demonstrated that RANTES and CpG ODN had capacities for mucosal adjuvanticity, i.e., for enhancing serum and vaginal antibodies specific to SIV Env, similar to those for CT. RANTES and CpG ODN skewed serum antibodies predominantly to the immunoglobulin G2a isotype. Most importantly, RANTES and CpG ODN were more effective than CT in increasing neutralizing titers of both serum and vaginal antibodies. After intranasal coadministration with VLPs, RANTES or CpG ODN also induced increased levels of gamma interferon (IFN-gamma)-producing lymphocyte and cytotoxic T-lymphocyte activities in both spleen and lymph nodes but did not increase the levels of interleukin-4-producing lymphocytes. The results suggest that RANTES and CpG ODN enhance immune responses in a T-helper-cell-type-1 (Th1)-oriented manner and that they can be used as effective mucosal adjuvants for enhancing both humoral and cellular immune responses in the context of VLPs, which are particulate antigens.

PMID: 12610137, UI: 22497625

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J Virol 2003 Mar;77(6):3487-94
 

A Japanese encephalitis virus peptide present on Johnson grass mosaic virus-like particles induces virus-neutralizing antibodies and protects mice against lethal challenge.

Saini M, Vrati S

National Institute of Immunology, New Delhi 110-067, India.

Protection against Japanese encephalitis virus (JEV) is antibody dependent, and neutralizing antibodies alone are sufficient to impart protection. Thus, we are aiming to develop a peptide-based vaccine against JEV by identifying JEV peptide sequences that could induce virus-neutralizing antibodies. Previously, we have synthesized large amounts of Johnson grass mosaic virus (JGMV) coat protein (CP) in Escherichia coli and have shown that it autoassembled to form virus-like particles (VLPs). The envelope (E) protein of JEV contains the virus-neutralization epitopes. Four peptides from different locations within JEV E protein were chosen, and these were fused to JGMV CP by recombinant DNA methods. The fusion protein autoassembled to form VLPs that could be purified by sucrose gradient centrifugation. Immunization of mice with the recombinant VLPs containing JEV peptide sequences induced anti-peptide and anti-JEV antibodies. A 27-amino-acid peptide containing amino acids 373 to 399 from JEV E protein, present on JGMV VLPs, induced virus-neutralizing antibodies. Importantly, these antibodies were obtained without the use of an adjuvant. The immunized mice showed significant protection against a lethal JEV challenge.

PMID: 12610124, UI: 22497612

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JAMA 2003 Mar 26;289(12):1512-3
 

Inpatients at risk of contact vaccinia from immunized health care workers.

Smith PF, Chang HG, Sepkowitz KA

Publication Types:
 

• Letter

PMID: 12672767, UI: 22560882

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JAMA 2003 Mar 26;289(12):1497-8
 

From the Center of Disease Control and Prevention. Smallpox vaccine adverse events among civilians--United States, January 24-February 18, 2003.

PMID: 12672751, UI: 22560866

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JAMA 2003 Mar 26;289(12):1491
 

Critics bash HIV vaccine trial analysis.

Mitka M

Publication Types:
 

• News

PMID: 12672747, UI: 22560862

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JAMA 2003 Apr 2;289(13):1629-30
 

From the Centers for Disease Control and Prevention. Vaccination coverage among children enrolled in Head Start programs, licensed child care facilities, and entering school--United States, 2000-01 school year.

[Medline record in process]
 

PMID: 12672721, UI: 22560898

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JAMA 2003 Apr 2;289(13):1627-8
 

From the Centers for Disease Control and Prevention. Smallpox vaccine adverse events among civilians--United States, February 18-24, 2003.

[Medline record in process]
 

PMID: 12672719, UI: 22560896

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MMWR Morb Mortal Wkly Rep 2003 Mar 21;52(11):228-9
 

Absence of transmission of the d9 measles virus--Region of the Americas, November 2002-March 2003.

In 1994, countries of the Region of the Americas set a goal of interrupting indigenous measles transmission, and the regional plan of action for achieving this goal was begun in 1996. As of March 16, 2003, the Region of the Americas has been free for 17 weeks from known circulation of the d9 measles virus, the strain responsible for the only large outbreak of measles in the region during 2002 (Figure).

PMID: 12665116, UI: 22551209

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N Engl J Med 2003 Apr 3;348(14):1405-7; author reply 1405-7
 

An outbreak of varicella despite vaccination.

Giusti RJ

Publication Types:
 

• Comment
• Letter

PMID: 12672872, UI: 22561063

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N Engl J Med 2003 Apr 3;348(14):1402-5; author reply 1402-5
 

A human papillomavirus type 16 vaccine.

Duggirala MK, Cuddihy MT

Publication Types:
 

• Comment
• Letter

PMID: 12672871, UI: 22561062

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N Engl J Med 2003 Apr 3;348(14):1322-32
 

Influenza vaccination and reduction in hospitalizations for cardiac disease and stroke among the elderly.

Nichol KL, Nordin J, Mullooly J, Lask R, Fillbrandt K, Iwane M

Veterans Affairs Medical Center and the University of Minnesota, Minneapolis 55417, USA. nicho014@umn.edu

BACKGROUND: Upper respiratory tract illnesses have been associated with an increased risk of ischemic heart disease and stroke. During two influenza seasons, we assessed the influence of vaccination against influenza on the risk of hospitalization for heart disease and stroke, hospitalization for pneumonia and influenza, and death from all causes. METHODS: Cohorts of community-dwelling members of three large managed-care organizations who were at least 65 years old were studied during the 1998-1999 and 1999-2000 influenza seasons. Administrative and clinical data were used to evaluate outcomes, with multivariable logistic regression to control for base-line demographic and health characteristics of the subjects. RESULTS: There were 140,055 subjects in the 1998-1999 cohort and 146,328 in the 1999-2000 cohort, of which 55.5 percent and 59.7 percent, respectively, were immunized. At base line, vaccinated subjects were on average sicker, having higher rates of most coexisting conditions, outpatient care, and prior hospitalization for pneumonia than unvaccinated subjects. Unvaccinated subjects, however, were more likely to have been given a prior diagnosis of dementia or stroke. Vaccination against influenza was associated with a reduction in the risk of hospitalization for cardiac disease (reduction of 19 percent during both seasons [P<0.001]), cerebrovascular disease (reduction of 16 percent during the 1998-1999 season [P<0.018] and 23 percent during the 1999-2000 season [P<0.001]), and pneumonia or influenza (reduction of 32 percent during the 1998-1999 season [P<0.001] and 29 percent during the 1999-2000 season [P<0.001]) and a reduction in the risk of death from all causes (reduction of 48 percent during the 1998-1999 season [P<0.001] and 50 percent during the 1999-2000 season [P<0.001]). In analyses according to age, the presence or absence of major medical conditions at base line, and study site, the findings were consistent across all subgroups. CONCLUSIONS: In the elderly, vaccination against influenza is associated with reductions in the risk of hospitalization for heart disease, cerebrovascular disease, and pneumonia or influenza as well as the risk of death from all causes during influenza seasons. These findings highlight the benefits of vaccination and support efforts to increase the rates of vaccination among the elderly. Copyright 2003 Massachusetts Medical Society

PMID: 12672859, UI: 22561050

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Nat Med 2003 Apr;9(4):376
 

AIDSVAX flop leaves vaccine field unscathed.

Ready T

Boston.

[Medline record in process]
 

PMID: 12669041, UI: 22559780

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Pediatr Infect Dis J 2003 Feb;22(2 Suppl):S100-3; discussion S103-4
 

Mucosal gene expression vaccine: a novel vaccine strategy for respiratory syncytial virus.

Mohapatra SS

Dept. of Internal Medicine, Div. of Allergy and Immunology, Joy McCann Culverhouse Airway Disease Research Center, University of South Florida College of Medicine/VA Hospital, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612, USA. smohapat@hsc.usf.edu

[Medline record in process]
 

A number of approaches have been used in attempts to develop a safe and effective vaccine for respiratory syncytial virus (RSV) infection. This article describes an effective prophylactic intranasal gene transfer strategy utilizing chitosan-DNA nanospheres [the mucosal gene expression vaccine (MGXV)], containing a mixture of plasmid DNAs encoding RSV antigens. In a mouse model of RSV infection, a single administration of MGXV (25 microg/mouse) results in a significant reduction of viral titers and viral antigen load after acute RSV infection of these mice. MGXV-treated mice show no significant change in airway reactivity to methacholine and no apparent pulmonary inflammation. Together these results demonstrate the potential of MGXV against acute RSV infection.

PMID: 12671460, UI: 22558376

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Pediatr Infect Dis J 2003 Feb;22(2 Suppl):S94-9
 

Clinical experience with respiratory syncytial virus vaccines.

Piedra PA

Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. ppiedra@bcm.tmce.edu

[Medline record in process]
 

Respiratory syncytial virus (RSV) infection is at times associated with life-threatening lower respiratory tract illness in infancy. Severe infection during the first year of life may be an important risk factor or indicator for the development of asthma in early childhood. Severe infections primarily occur in healthy infants, and young infants and children with specific risk factors. However, RSV causes respiratory infections in all age groups. Indeed it is now recognized that RSV disease is responsible for significant morbidity and mortality in the geriatric population. RSV infection remains difficult to treat, and prevention is a worldwide goal. For this reason there has been an intensive effort to develop an effective and safe RSV vaccine. Initial infection with RSV affords limited protection to reinfection, yet repeated episodes decrease the risk for lower respiratory tract illness. In the 20 years from 1960 to 1980, trials of several candidate RSV vaccines failed to attain the desired safety and protection against natural infection. Some vaccine types either failed to elicit immunogenicity, as with the live subcutaneous vaccine, or resulted in exaggerated disease on natural exposure to the virus, as with the formalin-inactivated (FI) type. Currently vaccine candidates are being developed based on the molecular virology of RSV. Recent formulations of candidate RSV vaccines have focused on subunit vaccines [such as purified fusion protein (PFP)], subunit vaccines combined with nonspecific immune activating adjuvants, live attenuated vaccines (including cold passaged, temperature-sensitive or cpts mutants), genetically engineered live attenuated vaccines and polypeptide vaccines.

PMID: 12671459, UI: 22558375

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Pediatrics 2003 Apr;111(4 Pt 1):922-3
 

Ethylmercury in vaccines.

Coleman E

[Medline record in process]
 

Publication Types:
 

• Comment
• Letter

PMID: 12671140, UI: 22558420

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Pediatrics 2003 Apr;111(4 Pt 1):896-9
 

Incidence of invasive pneumococcal disease in children 3 to 36 months of age at a tertiary care pediatric center 2 years after licensure of the pneumococcal conjugate vaccine.

Lin PL, Michaels MG, Janosky J, Ortenzo M, Wald ER, Mason EO Jr

Division of Pediatric Infectious Diseases, Children's Hospital of Pittsburgh, PA 15213, USA.

[Medline record in process]
 

PMID: 12671130, UI: 22558410

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Wkly Epidemiol Rec 2003 Feb 28;78(9):62-3
 

WHO/UNAIDS HIV vaccine initiative calls for accelerated research to build on trial accomplishments.

[Medline record in process]
 

PMID: 12666273, UI: 22553339

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Wkly Epidemiol Rec 2003 Feb 28;78(9):58-62
 

Recommended composition of influenza virus vaccines for use in the 2003-2004 influenza season.

[Medline record in process]
 

PMID: 12666272, UI: 22553338

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