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Infect Immun 2002 Nov;70(11):6409-15
 

Immunization with C5a Peptidase or Peptidase-Type III Polysaccharide Conjugate Vaccines Enhances Clearance of Group B Streptococci from Lungs of Infected Mice.

Cheng Q, Debol S, Lam H, Eby R, Edwards L, Matsuka Y, Olmsted SB, Cleary PP

Department of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455. Wyeth-Lederle Vaccines, Rochester, New York 14586.

[Medline record in process]
 

Group B streptococci (GBS) are among the most common causes of life-threatening neonatal infections. Vaccine development since the late 1970s has focused on the capsular polysaccharides, but a safe, effective product is still not available. Our quest for a vaccine turned to the streptococcal C5a peptidase (SCPB). This surface protein is antigenically conserved across most if not all serotypes. A murine model was used to assess the impact of SCPB on clearance of GBS from the lungs of intranasally infected animals. Mutational inactivation of SCPB resulted in more-rapid clearance of streptococci from the lung. Immunization with recombinant SCPB alone or SCPB conjugated to type III capsular polysaccharide produced serotype-independent protection, which was evidenced by more-rapid clearance of the serotype VI strain from the lungs. Immunization of mice with tetanus toxoid-type III polysaccharide conjugate did not produce protection, confirming that protection induced by SCPB conjugates was independent of type III polysaccharide antigen. Histological evaluation of lungs from infected mice revealed that pathology in animals immunized with SCPB or SCPB conjugates was significantly less than that in animals immunized with a tetanus toxoid-polysaccharide conjugate. These experiments suggest that inclusion of C5a peptidase in a vaccine will both add another level to and broaden the spectrum of the protection of a polysaccharide vaccine.

PMID: 12379721, UI: 22267139

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Infect Immun 2002 Nov;70(11):6383-8
 

Protection against Experimental Helicobacter pylori Infection after Immunization with Inactivated H. pylori Whole-Cell Vaccines.

Raghavan S, Hjulstrom M, Holmgren J, Svennerholm AM

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

[Medline record in process]
 

The protective effect of therapeutic oral immunization with homologous and heterologous formalin-inactivated Helicobacter pylori cells given together with cholera toxin as an adjuvant was evaluated with C57BL/6 mice infected with H. pylori Sydney strain 1 (SS1). The bacteria used for immunization were strains that were either homologous or heterologous with regard to the O antigen (i.e., the Lewis antigen [Le antigen]) expressed by the lipopolysaccharide of the infecting H. pylori SS1 strain. We found that repeated oral immunization with inactivated H. pylori SS1 cells can significantly inhibit an existing infection (P < 0.001) and that the protection induced by such therapeutic immunization extends to protection against reinfection (P < 0.001). A similar level of protection was also achieved by immunization with another inactivated H. pylori strain having the same O antigen (Le antigen) as the infecting H. pylori SS1 strain. In contrast, immunization with inactivated strains expressing a heterologous O antigen, Le(x), provided less protection or no protection. Immunization with H. pylori lysate preparations, on the other hand, resulted in significant comparable protection whether the lysates were prepared from an Le(x) strain or an Le(y) strain. Postimmunization gastritis was seen in mice that were protected after vaccination but not in unimmunized or unprotected mice. In conclusion, therapeutic immunization with inactivated H. pylori whole-cell vaccines may provide strong protection both against experimental H. pylori infection and against later reinfection.

PMID: 12379718, UI: 22267136

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Infect Immun 2002 Nov;70(11):6188-95
 

Clinical and immune impact of Mycobacterium bovis BCG vaccination scarring.

Jason J, Archibald LK, Nwanyanwu OC, Kazembe PN, Chatt JA, Norton E, Dobbie H, Jarvis WR

HIV Immunology and Diagnostics Branch, Division of AIDS, STD, and TB Laboratory Research, Centers for Disease Control and Prevention, U. S. Public Health Service, U.S. Department of Health and Human Services, Atlanta, Georgia 30333, USA. JMJ1@cdc.gov

[Medline record in process]
 

The World Health Organization recommends Mycobacterium bovis BCG vaccination in areas of high tuberculosis prevalence. BCG's clinical and immune effects, not necessarily Mycobacterium tuberculosis specific, are unclear. BCG vaccine scarring often is used as a surrogate marker of vaccination or of effective vaccination. We evaluated BCG scarring status in relation to clinical findings and outcome in 700 hospitalized Malawians, of whom 32 had M. tuberculosis bloodstream infections (BSI) (10 of whom had cellular immune studies done) and of whom 48 were infants <6 months old and therefore recently vaccinated (19 of whom had immune studies). In the patients >/=6 months old, scarring was not related to the presence of pulmonary symptoms (35 versus 30%), chronic cough or fever, mortality, or M. tuberculosis BSI. In M. tuberculosis BSI patients, scarring was unrelated to mortality, vital signs, or clinical symptoms but those with scarring had higher proportions of memory and activated T cells and more type 2-skewed cytokine profiles. Infants with either BCG scarring (n = 10) or BCG lesional inflammation (n = 5) had no symptoms of sepsis, but 18 of 33 infants without BCG vaccination lesions did. Those with BCG lesions had localized infections more often than did those without BCG lesions. These infants also had lower median percentages of lymphocytes spontaneously making interleukin-4 (IL-4) or tumor necrosis factor alpha (TNF-alpha) and lower ratios of T cells spontaneously making IL-4 to T cells making IL-6. Thus, we found that, in older patients, BCG vaccine scarring was not associated with M. tuberculosis-specific or nonspecific clinical protection. Those with M. tuberculosis BSI and scarring had immune findings suggesting previous M. tuberculosis antigen exposure and induction of a type 2 cytokine pattern with acute reexposure. It is unlikely that this type 2 pattern would be protective against mycobacteria, which require a type 1 response for effective containment. In infants <6 months old, recent BCG vaccination was associated with a non-M. tuberculosis-specific, anti-inflammatory cytokine profile. That the vaccinated infants had a greater frequency of localized infections and lesser frequency of sepsis symptoms suggests that this postvaccination cytokine pattern may provide some non-M. tuberculosis-specific clinical benefits.

PMID: 12379697, UI: 22267115

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Infect Immun 2002 Nov;70(11):6147-57
 

Evaluation of type 1 immune response in naive and vaccinated animals following challenge with Leptospira borgpetersenii serovar Hardjo: involvement of WC1(+) gammadelta and CD4 T cells.

Naiman BM, Blumerman S, Alt D, Bolin CA, Brown R, Zuerner R, Baldwin CL

Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, Massachusetts 01003, USA.

[Medline record in process]
 

Organisms within the Hardjo serovar of Leptospira species are harbored in cattle throughout the world, causing abortion in pregnant animals as well as being shed in the urine, thereby providing sources of zoonotic infection for humans. We recently showed that sterile immunity in vaccinated cattle is associated with induction of a type 1 (Th1) cell-mediated immune response. Here naive and previously vaccinated pregnant cattle were challenged with a virulent strain of serovar Hardjo and subsequently evaluated for expression of a type 1 immune response. Lymphocytes that responded in a recall response to antigen by undergoing blast transformation were evident in cultures of peripheral blood mononuclear cells (PBMC) from vaccinated cattle throughout the postchallenge test period while those from naive cattle were evident at one time point only. Nevertheless, beginning at 2 weeks after challenge, gamma interferon (IFN-gamma) was measured in supernatants of antigen-stimulated PBMC cultures from nonvaccinated animals although the amount produced was always less than that in cultures of PBMC from vaccinated animals. IFN-gamma(+) cells were also evident in antigen-stimulated cultures of PBMC from vaccinated but not from nonvaccinated animals throughout the postchallenge period. The IFN-gamma(+) cells included CD4(+) and WC1(+) gammadelta T cells, and a similar proportion of these two subpopulations were found among the dividing cells in antigen-stimulated cultures as ascertained by carboxyfluorescein succinimidyl ester loading. Finally, while naive and vaccinated animals had similar levels of antigen-specific immunoglobulin G1 (IgG1) following challenge, vaccinated animals had twofold-more IgG2. In conclusion, while infection may induce a type 1 response we suggest that it is too weak to prevent establishment of chronic infection.

PMID: 12379692, UI: 22267110

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Infect Immun 2002 Nov;70(11):6013-20
 

Nature and specificity of the required protective immune response that develops postchallenge in mice vaccinated with the 19-kilodalton fragment of Plasmodium yoelii merozoite surface protein 1.

Wipasa J, Xu H, Makobongo M, Gatton M, Stowers A, Good MF

Cooperative Research Center for Vaccine Technology, Queensland Institute of Medical Research, Herston, Queensland 4029, Australia.

[Medline record in process]
 

Immunity induced by the 19-kDa fragment of Plasmodium yoelii merozoite surface protein 1 (MSP1(19)) is dependent on high titers of specific antibodies present at the time of challenge and a continuing active immune response postinfection. However, the specificity of the active immune response postinfection has not been defined. In particular, it is not known whether anti-MSP1(19) antibodies that arise following infection alone are sufficient for protection. We developed systems to investigate whether an MSP1(19)-specific antibody response alone both prechallenge and postchallenge is sufficient for protection. We were able to exclude antibodies with other specificities, as well as any contribution of MSP1(19)-specific CD4(+) T cells acting independent of antibody, and we concluded that an immune response focused solely on MSP1(19)-specific antibodies is sufficient for protection. The data imply that the ability of natural infection to boost an MSP1(19)-specific antibody response should greatly improve vaccine efficacy.

PMID: 12379677, UI: 22267095

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Infect Immun 2002 Nov;70(11):5982-9
 

Specific Immune Responses and Enhancement of Murine Pulmonary Clearance of Moraxella catarrhalis by Intranasal Immunization with a Detoxified Lipooligosaccharide Conjugate Vaccine.

Jiao X, Hirano T, Hou Y, Gu XX

National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland 20850.

[Medline record in process]
 

Moraxella catarrhalis is an important human mucosal pathogen. This study investigated the effect of intranasal immunization with a detoxified-lipooligosaccharide-cross-reactive mutant of diphtheria toxin (dLOS-CRM) vaccine candidate on pulmonary clearance following an aerosol challenge of mice with M. catarrhalis. Intranasal immunization with dLOS-CRM plus cholera toxin induced a significantly dose-dependent increase of immunoglobulin A (IgA) and IgG in the nasal wash, lung lavage fluid, saliva, and fecal extract. In addition, serum IgG, IgM, and IgA against LOS of M. catarrhalis were detected. LOS-specific antibody-forming cells were found in the nasal passages, spleens, nasally associated lymphoid tissues, cervical lymph nodes, lungs, and Peyer's patches using an enzyme-linked immunospot assay. The dLOS-CRM vaccine induced a significant bacterial clearance (70 to 90%) of both homologous and heterologous strains in the lungs compared to that observed in the controls (P < 0.01). Intriguingly, intranasal immunization with dLOS-CRM showed a higher level of bacterial clearance compared with subcutaneous injections with dLOS-CRM. These data indicate that dLOS-CRM induces specific mucosal and systemic immunity through intranasal immunization and also provides effective bacterial clearance. On the basis of these results, we believe that dLOS-CRM should undergo continued testing to determine whether it would induce protective immune response in humans.

PMID: 12379673, UI: 22267091

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Infect Immun 2002 Oct;70(10):5589-95
 

Enhanced immunogenicity of pneumococcal surface adhesin A by genetic fusion to cytokines and evaluation of protective immunity in mice.

Gor DO, Ding X, Li Q, Schreiber JR, Dubinsky M, Greenspan NS

Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4943, USA.

Immunization of mice with pneumococcal surface adhesin A (PsaA) emulsified in complete Freund's adjuvant (CFA) provides protection against systemic infection with Streptococcus pneumoniae. Because the use of CFA is not acceptable in humans, we sought to develop alternative means of enhancing the immunogenicity of protein antigens of potential use in pneumococcal vaccines. We designed a series of genetic constructs in which coding sequences for PsaA were linked to sequences encoding either murine interleukin-2 (mIL-2), mIL-4, or two copies of an immunostimulatory nonapeptide derived from mIL-1beta. The PsaA-cytokine constructs were cloned and expressed in Escherichia coli. Mice immunized twice with PsaA-IL-2, or PsaA-IL-4 responded with PsaA-specific antibody production comparable in magnitude to that of mice primed with PsaA in CFA and boosted with PsaA in incomplete Freund's adjuvant (PsaA-Adj). Antibodies elicited by PsaA-Adj were predominantly of the immunoglobulin G1 (IgG1) subclass, while PsaA-IL-2 and PsaA-IL-4 elicited substantial amounts of IgG2a in addition to IgG1. Mice immunized with PsaA-Adj or PsaA-IL-4 were partially protected against intraperitoneal challenge with virulent S. pneumoniae (30% overall survival beyond 15 days postchallenge). Mice immunized with PsaA and no adjuvant or PsaA-IL-2 exhibited 0 or 5% survival rates, respectively, following challenge. In contrast, mice immunized twice with capsular polysaccharide were 100% protected. The modest levels of protection seen in mice immunized with PsaA and its more immunogenic derivatives may be explained in part by the relative inaccessibility of antibody to PsaA on the surface of encapsulated S. pneumoniae.

PMID: 12228286, UI: 22215692

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Infect Immun 2002 Oct;70(10):5579-88
 

Tissue selectivity of interferon-stimulated gene expression in mice infected with Dam(+) versus Dam(-) Salmonella enterica serovar Typhimurium strains.

Shtrichman R, Heithoff DM, Mahan MJ, Samuel CE

Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California 93106, USA.

The host interferon (IFN) system plays an important role in protection against microbial infections. Salmonella enterica serovar Typhimurium is highly virulent in the mouse model, whereas mutants that lack DNA adenine methylase (Dam(-)) are highly attenuated and elicit fully protective immune responses against murine typhoid fever. We examined the expression of IFN-responsive genes in several mouse tissues following infection with Dam(+) or Dam(-) SALMONELLA: Infection of mice with Dam(+) Salmonella resulted in the induction of host genes known to be indicators of IFN bioactivity and regulated by either IFN-alpha/beta (Mx1) or IFN-gamma (class II transactivator protein [CIITA] and inducible nitric oxide synthase [iNOS]) or by both IFN-alpha/beta and IFN-gamma (RNA-specific adenosine deaminase [ADAR1] and RNA-dependent protein kinase [PKR]) in a tissue-specific manner compared to uninfected animals. Since the Mx1 promoter is IFN-alpha/beta specific and the Mx1 gene is not inducible directly by IFN-gamma, these data suggest a role of IFN-alpha/beta in the host response to Salmonella infection. Mice infected with Dam(-) Salmonella showed reduced expression of the same set of IFN-stimulated genes (ISGs) as that observed after infection with wild-type SALMONELLA: The reduced capacity to induce ISGs persisted in Dam(-)-vaccinated mice after challenge with the virulent (Dam(+)) strain. Finally, although no Dam(-) organisms were recovered from the liver or spleen after oral infection of mice, ADAR, PKR, Mx, and CIITA expression levels were elevated in these tissues relative to those in uninfected mice, suggestive of the distant action of a signaling molecule(s) in the activation of ISG expression.

PMID: 12228285, UI: 22215691

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Infect Immun 2002 Oct;70(10):5521-32
 

Major histocompatibility complex class II DR-restricted memory CD4(+) T lymphocytes recognize conserved immunodominant epitopes of Anaplasma marginale major surface protein 1a.

Brown WC, McGuire TC, Mwangi W, Kegerreis KA, Macmillan H, Lewin HA, Palmer GH

Program in Vector-Borne Diseases, Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164, USA. wbrown@vetmed.wsu.edu

Native major surface protein 1 (MSP1) of Anaplasma marginale, composed of covalently associated MSP1a and MSP1b proteins, stimulates protective immunity in cattle against homologous and heterologous strain challenge. Protective immunity against pathogens in the family Anaplasmataceae involves both CD4(+) T cells and neutralizing immunoglobulin G. Thus, an effective vaccine should contain both CD4(+) T- and B-lymphocyte epitopes that will elicit strong memory responses upon infection with homologous and heterologous strains. Previous studies demonstrated that the predominant CD4(+) T-cell response in MSP1 vaccinates is directed against the MSP1a subunit. The present study was designed to identify conserved CD4(+) T-cell epitopes in MSP1a presented by a broadly represented subset of major histocompatibility complex (MHC) class II molecules that would be suitable for inclusion in a recombinant vaccine. Transmembrane protein prediction analysis of MSP1a from the Virginia strain revealed a large hydrophilic domain (HD), extending from amino acids (aa) 1 to 366, and a hydrophobic region extending from aa 367 to 593. The N terminus (aa 1 to 67) includes one 28-aa form A repeat and one 29-aa form B repeat, which each contain an antibody neutralization-sensitive epitope [Q(E)ASTSS]. In MSP1 vaccinates, recombinant MSP1a HD (aa 1 to 366) stimulated recall proliferative responses that were comparable to those against whole MSP1a excluding the repeat region (aa 68 to 593). Peptide mapping determined a minimum of five conserved epitopes in aa 151 to 359 that stimulated CD4(+) T cells from cattle expressing DR-DQ haplotypes common in Holstein-Friesian breeds. Peptides representing three epitopes (aa 231 to 266, aa 270 to 279, and aa 290 to 319) were stimulatory for CD4(+) T-cell clones and restricted by DR. A DQ-restricted CD4(+) T-cell epitope, present in the N-terminal form B repeat (VSSQSDQASTSSQLG), was also mapped using T-cell clones from one vaccinate. Although form B repeat-specific T cells did not recognize the form A repeat peptide (VSSQS_EASTSSQLG), induction of T-cell anergy by this peptide was ruled out. The presence of multiple CD4(+) T-cell epitopes in the MSP1a HD, in addition to the neutralization-sensitive epitope, supports the testing of this immunogen for induction of protective immunity against A. marginale challenge.

PMID: 12228278, UI: 22215684

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Infect Immun 2002 Oct;70(10):5446-53
 

Epitope mapping of the immunodominant antigen TB10.4 and the two homologous proteins TB10.3 and TB12.9, which constitute a subfamily of the esat-6 gene family.

Skjot RL, Brock I, Arend SM, Munk ME, Theisen M, Ottenhoff TH, Andersen P

Department of TB Immunology, Statens Serum Institute, Copenhagen, Denmark.

The human T-cell recognition of the low-molecular-mass culture filtrate antigen TB10.4 was evaluated in detail. The molecule was strongly recognized by T cells isolated from tuberculosis (TB) patients and from BCG-vaccinated donors. The epitopes on TB10.4 were mapped with overlapping peptides and found to be distributed throughout the molecule. The broadest response was found in TB patients, whereas the response in BCG-vaccinated donors was focused mainly toward a dominant epitope located in the N terminus (amino acids 1 to 18). The gene encoding TB10.4 was found to belong to a subfamily within the esat-6 family that consists of the three highly homologous proteins TB10.4, TB10.3, and TB12.9 (Rv0288, Rv3019c, and Rv3017c, respectively). Southern blot analysis combined with database searches revealed that the three members of the TB10.4 family were present only in strains of the Mycobacterium tuberculosis complex, including BCG, and M. kansasii, whereas other atypical mycobacteria had either one (M. avium, M. intracellulare, and M. marinum) or none (M. scrofulaceum, M. fortuitum, and M. szulgai) of the genes. The fine specificity of the T-cell response to the three closely related esat-6 family members was markedly different, with only a few epitopes shared between the molecules. Minimal differences in the amino acid sequence translated into large differences in recognition by T cells and secretion of gamma interferon. In general, the peptides from TB10.4 stimulated the largest responses, but epitopes unique to both TB10.3 and TB12.9 were found. The relevance of the findings for TB vaccine development and as a potential mechanism for immune evasion is discussed.

PMID: 12228269, UI: 22215675

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J Virol 2002 Oct;76(20):10346-55
 

Exchange of the C-terminal part of VP3 from very virulent infectious bursal disease virus results in an attenuated virus with a unique antigenic structure.

Boot HJ, ter Huurne AA, Hoekman AJ, Pol JM, Gielkens AL, Peeters BP

Institute for Animal Science and Health, ID-Lelystad, PO Box 65, NL-8200 AB Lelystad, The Netherlands. H.J.Boot@id.wag-ur.nl

Infectious bursal disease virus (IBDV) is the major viral pathogen in the poultry industry. Live attenuated serotype 1 vaccine strains are commonly used to protect susceptible chickens during their first 6 weeks of life. Wild-type serotype 1 IBDV strains are highly pathogenic only in chickens, whereas serotype 2 strains are apathogenic in chickens and other birds. Here we describe the replacement of the genomic double-stranded RNA (dsRNA) encoding the N- or C-terminal part of VP3 of serotype 1 very virulent IBDV (vvIBDV) (isolate D6948) with the corresponding part of serotype 2 (isolate TY89) genomic dsRNA. The modified virus containing the C-terminal part of serotype 2 VP3 significantly reduced the virulence in specific-pathogen-free chickens, without affecting the distinct bursa tropism of serotype 1 IBDV strains. Furthermore, by using serotype-specific antibodies we were able to distinguish bursas infected with wild-type vvIBDV from bursas infected with the modified vvIBDV. We are currently evaluating the potential of this recombinant strain as an attenuated live vaccine that induces a unique serological response (i.e., an IBDV marker vaccine).

PMID: 12239311, UI: 22224747

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J Virol 2002 Oct;76(20):10203-10
 

Gamma interferon-dependent protection of the mouse upper respiratory tract following parenteral immunization with a respiratory syncytial virus G protein fragment.

Plotnicky-Gilquin H, Cyblat-Chanal D, Aubry JP, Champion T, Beck A, Nguyen T, Bonnefoy JY, Corvaia N

Centre d'Immunologie Pierre Fabre, F74164 Saint-Julien-en-Genevois, France. helene.plotnicky.gilquin@pierre-fabre.com

The protective mechanisms induced in the mouse upper respiratory tract (URT) after intraperitoneal immunization with G2Na, a recombinant respiratory syncytial virus (RSV) G protein fragment (amino acid residues 130 to 230), were investigated. This protection was recently shown to be mediated by CD4(+) T cells and to be critically dependent on the cysteines and amino acids 193 and 194 (H. Plotnicky-Gilquin, A. Robert, L. Chevalet, J.-F. Haeuw, A. Beck, J.-Y. Bonnefoy, C. Brandt, C.-A. Siegrist, T. N. Nguyen, and U. F. Power, J. Virol. 74:3455-3463, 2000). On G2Na, we identified a domain (amino acid residues 182 to 198) responsible for the T-helper-cell activity. This region coincided with a peptide designed AICK (residues 184 to 198) which includes the previously identified murine and human T-helper-cell epitope on the native G protein (P. W. Tebbey, M. Hagen, and G. E. Hancock, J. Exp. Med. 188:1967-1972, 1998). Immunization with AICK, in alum or complete Freund's adjuvant, significantly reduced nasal RSV titers in normal BALB/c mice. However, although lung protection was induced, in contrast to the case with live RSV, neither AICK nor G2Na was able to prevent nasal infection in gamma interferon (IFN-gamma)-knockout mice. Anti-IFN-gamma neutralizing antibodies partially inhibited URT protection after administration to G2Na-immunized BALB/c mice. Furthermore, while purified CD4(+) T cells from BALB/c mice immunized with G2Na or AICK significantly reduced lung and nasal infection of naive recipient mice after adoptive transfer, the cells from IFN-gamma-knockout mice had no effect. Together, these results demonstrated for the first time that the T-helper-cell epitope of RSV G protein induces URT protection in mice after parenteral immunization through a Th1-type, IFN-gamma-dependent mechanism.

PMID: 12239295, UI: 22224731

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JAMA 2002 Oct 16;288(15):1901-5
 

Contact vaccinia--transmission of vaccinia from smallpox vaccination.

Neff JM, Lane JM, Fulginiti VA, Henderson DA

Center for Children With Special Needs, Children's Hospital, and the Department of Pediatrics, University of Washington School of Medicine, 4800 Sand Point Way NE, CM:09, Seattle, WA 98105-0371, USA. jneff@chmc.org

Publication Types:
 

• Review
• Review, multicase

PMID: 12377090, UI: 22265848

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JAMA 2002 Oct 9;288(14):1713-4
 

From the Centers for Disease Control and Prevention. National, state, and urban area vaccination levels among children aged 19-35 months--United States, 2001.

PMID: 12375590, UI: 22261686

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Lancet 2002 Sep 28;360(9338):991
 

Differential genetic determination of immune responsiveness to hepatitis B surface antigen and to hepatitis A virus: a vaccination study in twins.

Hohler T, Reuss E, Evers N, Dietrich E, Rittner C, Freitag C, Vollmar J, Schneider P, Fimmers R

Department of Internal Medicine, Johannes Gutenberg-University, Mainz, Germany

[Medline record in process]
 

Background The course of viral hepatitis is thought to be affected by genetic host variability and, in particular, by genes of the major histocompatibility locus. Hepatitis A and B vaccination is a useful model to study the effect of host factors on the immune response to viral antigens. We aimed to assess the heritability of the HBsAg (anti-HBs) and anti-hepatitis A virus (anti-HAV) immune response and to estimate the effect of the HLA-DRB1 locus and other genetic loci unlinked to HLA.Methods We did an open prospective study and vaccinated 202 twin pairs with a combined recombinant HBsAg/inactivated hepatitis A vaccine. We measured antibodies to HBsAg and HAV and determined HLA-DRB1* alleles. Heritability was calculated based on variance of antibody response within pairs. Model-fitting analyses were done to analyse genetic and environmental components of vaccine responses.Findings Anti-HBs and anti-HAV showed heritabilities of 0.61 (95% CI 0.41 to 0.81) and 0.36 (-0.02 to 0.73), respectively. For the anti-HBs immune response, 60% of the phenotypic variance was explained by additive genetic and 40% by non-shared environmental effects. The heritability of the HBsAg vaccine response accounted for by the DRB1* locus was estimated to be 0.25, leaving the remaining heritability of 0.36 to other gene loci.Interpretation Genetic factors have a strong effect on the immune response to HBsAg. Although genes encoded within the MHC are important for this immune response, more than half the heritability is determined outside this complex. Identification of these genes will help us to understand regulation of immune responses to viral proteins.

PMID: 12383669, UI: 22272036

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MMWR Morb Mortal Wkly Rep 2002 Oct 4;51(39):880-2
 

Update: Influenza activity--United States and worldwide, June-September, 2002.

During June-September 2002, influenza A (H3N2) and B viruses circulated worldwide and were associated with mild to moderate levels of disease activity. Influenza B viruses predominated in Africa, and both influenza A (H3N2) and B viruses circulated widely in Asia, Oceania, and Latin America, except in Chile and Taiwan, where A (H1) viruses predominated. In North America, sporadic isolates of influenza A (H3N2), A (H1), and B viruses were identified. This report summarizes influenza activity in the United States and worldwide during June-September 2002. Influenza activity in North America typically peaks during December-March, which underscores the need to begin vaccinating against influenza in October and to continue vaccination into December and throughout the influenza season.

PMID: 12375689, UI: 22262647

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Nat Med 2002 Oct 15;
 

Generation of antibodies specific for beta-amyloid by vaccination of patients with Alzheimer disease.

Hock C, Konietzko U, Papassotiropoulos A, Wollmer A, Streffer J, Von Rotz RC, Davey G, Moritz E, Nitsch RM

[1] Division of Psychiatry Research, University of Zurich, Zurich, Switzerland [2] C.H. and U.K. contributed equally to this study.

[Record supplied by publisher]
 

To characterize antibodies produced in humans in response to Abeta(42) vaccination, we carried out immunohistochemical examinations of the brains of both transgenic mice and human patients with beta-amyloid pathology. We collected sera from patients with Alzheimer disease who received a primary injection of pre-aggregated Abeta(42) followed by one booster injection in a placebo-controlled study. Antibodies in immune sera recognized beta-amyloid plaques, diffuse Abeta deposits and vascular beta-amyloid in brain blood vessels. The antibodies did not cross-react with native full-length beta-amyloid precursor protein or its physiological derivatives, including soluble Abeta(42). These findings indicate that vaccination of AD patients with Abeta(42) induces antibodies that have a high degree of selectivity for the pathogenic target structures. Whether vaccination to produce antibodies against beta-amyloid will halt the cognitive decline in AD will depend upon clinical assessments over time.

PMID: 12379846

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Pediatr Infect Dis J 2002 Apr;21(4):357-8
 

Chronic maternal hepatitis B infection and premature rupture of membranes.

Fiore AE

Division of Viral Hepatitis, Center for Disease Control and Prevention, Atlanta, GA, USA.

PMID: 12075775, UI: 22071003

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Pediatr Infect Dis J 2002 Apr;21(4):350-2
 

Safety, tolerability and immunogenicity of low dose Haemophilus influenzae type b conjugated to the outer membrane protein complex of Neisseria meningitidis group B.

Anderson EL, Frey S, Geldmacher K, Radley D, Lee A, Donnelly J, Mendelman PM, Dargan JM, Kaplan KM

Saint Louis University Health Sciences Center Division of Infectious Disease and Immunology, St Louis, MO, USA.

Infants vaccinated with three doses followed by a booster of either 1.0 microg of Haemophilus influenzae type b conjugated to the outer membrane protein complex of Neisseria meningitidis group B or H. influenzae 10-microg oligosaccharide vaccine conjugated to 25 microg mutant toxin (CRM197) isolated from Corynebacterium diphtheriae had protective antipolyribosylribitol phosphate concentrations.

Publication Types:
 

• Clinical trial

PMID: 12075771, UI: 22070999

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Pediatr Infect Dis J 2002 Apr;21(4):278-82
 

Invasive pneumococcal infections in children with asplenia.

Schutze GE, Mason EO Jr, Barson WJ, Kim KS, Wald ER, Givner LB, Tan TQ, Bradley JS, Yogev R, Kaplan SL

Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, USA. schutzegordone@uams.edu

BACKGROUND: Asplenia is associated with an increased risk of infections caused by Streptococcus pneumoniae. Overwhelming infection can be fulminate and lead to a fatal outcome. OBJECTIVE: To review the epidemiology and clinical course of invasive S. pneumoniae infections in children with asplenia before the release of the conjugate pneumococcal vaccine. METHODS: Children with S. pneumoniae infections from eight children's hospitals in the US were identified prospectively from September, 1993, to August, 1999. Further demographic, medical and microbiologic information was gathered retrospectively from the charts of patients with asplenia. RESULTS: Twenty-two asplenic patients with 26 episodes of invasive S. pneumoniae were identified. This represents 1% of the 2,581 episodes of invasive S. pneumoniae infections identified in our study. Twelve had congenital asplenia (CA), and 10 had undergone surgical splenectomy. Nine of the patients with CA had associated complex congenital heart disease. The median age at first infection was 12.5 months for CA patients as compared with 69 months in children with surgical splenectomy (P < 0.001). Seventy-five percent of those eligible had received the polysaccharide pneumococcal vaccine. The most common serotypes isolated were 6B (8), 23F (7), 18C (2) and 19A (2). Antimicrobial prophylaxis had been prescribed for 82% of the study cohort. Clinical presentations of the 26 episodes included fever (22), shock (7), petechiae or purpura (7), disseminated intravascular coagulation (5) and respiratory distress (5). Clinical illness included bacteremia alone (12), meningitis alone (8), bacteremia with otitis media-sinusitis (3), bacteremia with pneumonia (2) and meningitis with osteomyelitis (1). Five of the 6 patients who died had meningitis. Three of the survivors (19%) had significant morbidity, and all of them had meningitis. Two patients had 2 episodes each, and 1 patient had 3 episodes. All but 1 of the multiple episodes was with a different serotype. Forty-six percent of isolates were nonsusceptible to penicillin, and 19% were nonsusceptible to ceftriaxone. There was no association between antimicrobial resistance and mortality. CONCLUSIONS: Invasive pneumococcal disease in patients with asplenia has a high mortality, especially in those with meningitis. Even though the new conjugate vaccine might increase protection, 19% of patients had disease caused by serotypes not included in the current heptavalent vaccine. Clinicians should continue to be aggressive in evaluating asplenic patients with unexplained fevers.

PMID: 12075756, UI: 22070984

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Pediatr Infect Dis J 2002 Apr;21(4):271-7
 

Relative frequency of Haemophilus influenzae type b pneumonia in Chinese children as evidenced by serology.

Wang YJ, Vuori-Holopainen E, Yang Y, Wang Y, Hu Y, Leboulleux D, Hedman K, Leinonen M, Peltola H

Beijing Children's Hospital, China.

OBJECTIVES: It is commonly held that Haemophilus influenzae pneumonia among children in Asia is mostly caused by serotypes other than b (Hib). If so, Hib conjugate vaccines would play little role in the prevention of pneumonia. In two prospective series of children hospitalized for pneumonia in China, the causative agents were searched for with a wide panel of microbiologic assays. METHODS: In the university hospitals of Beijing and Hefei, 156 consecutive children 3 months of age and older with symptoms and signs of pneumonia were studied. Blood culture, chest radiograph, nasopharyngeal aspirate for viral antigen detection and paired sera for 20 microbiologic assays were taken. Severity was graded, and the course of illness was monitored uniformly. RESULTS: In Beijing only likely contaminants grew from blood cultures, and in Hefei pathogens were identified in two cases. In combined series evidence for bacterial, mixed and viral etiology was obtained in 30, 7 and 21% of cases, respectively. The dominant bacteria were pneumococcus, Hib, Mycoplasma pneumoniae and Chlamydia pneumoniae, responsible for 13, 10, 8 and 8% of cases, respectively. Most patients were treated with extended spectrum antimicrobials such as piperacillin, cefotaxime or ceftriaxone, alone or in combination. One child died. CONCLUSIONS: As in most other series from other countries, the leading agent causing childhood pneumonia was pneumococcus but, in line with our previous experience from Beijing, the second most common agent detected was Hib. This observation suggests great potential for pneumococcal and Hib vaccinations in China. Because no evidence supported the need for routine use of extended spectrum antimicrobials, narrower spectrum agents would be safer for patients, would be cheaper for the community and would offer a way to address increasing resistance problems.

PMID: 12075755, UI: 22070983

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Wkly Epidemiol Rec 2002 Oct 4;77(40):331-9
 

Meningococcal vaccines: polysaccharide and polysaccharide conjugate vaccines.

[Medline record in process]
 

PMID: 12385146, UI: 22273388

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Wkly Epidemiol Rec 2002 Oct 4;77(40):330-1
 

Urgent call for action on meningitis in Africa--vaccine price and shortage are major obstacles.

[Medline record in process]
 

PMID: 12385145, UI: 22273387

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