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Pediatrics 2002 Feb;109(2):312-5
 

Why we need to know whether prophylactic antibiotics can reduce measles-related morbidity.

Chalmers I

UK Cochrane Centre, NHS Research and Development Programme, Summertown Pavilion, Middle Way, Oxford OX2 7LG, United Kingdom. ichalmers@cochrane.co.uk

In some parts of the world, measles vaccination has resulted in very substantial reductions in measles-related morbidity and mortality. Even so, it has been estimated that 30 million people still contract the disease every year, that nearly 1 million of these die, and that measles-related deaths account for about 10% of all deaths in children under the age of 5 in developing countries. Existing evidence from controlled trials suggests that antibiotic prophylaxis in measles can result in important reductions in measles-related morbidity, and, at a World Health Organization meeting convened in 1993 to decide on research priorities for the treatment of measles, highest priority was accorded to additional controlled trials of prophylactic antibiotics. As controlled trials of vitamin A in measles have made clear, such trials are feasible. Continued acquiescence in uncertainties about the effects of prophylactic antibiotics in a disease that continues to afflict so many children worldwide is unacceptable.

PMID: 11826211, UI: 21684059

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Pediatrics 2002 Feb;109(2):E22
 

Evaluating acceptability and completeness of overseas immunization records of internationally adopted children.

Schulte JM, Maloney S, Aronson J, San Gabriel P, Zhou J, Saiman L

Division of HIV/AIDS-Surveillance and Epidemiology, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. jzs1@cdc.gov

BACKGROUND: Increasing numbers of families in the United States are adopting children who were born in other countries. Appropriate immunization of internationally adopted children provides a challenge to pediatricians who must evaluate documentation of vaccines administered overseas and fulfill the recommended US childhood immunization schedule. The acceptability of vaccinations received outside the United States was addressed by the Advisory Committee on Immunization Practices in 1994, but few population-based studies assessing these vaccinations have been reported. METHODS: We performed a retrospective cohort study of 504 children who were adopted from other countries and evaluated in 1997 and 1998. Our goal was to determine the acceptability of overseas vaccinations for meeting US immunization requirements. We assessed immunization records for both valid documentation of receipt of vaccine and comparability with the recommended US schedule. We also determined the number of children who were up to date (UTD) for diphtheria-tetanus-pertussis, polio, hepatitis B, and measles-mumps-rubella vaccines under the US schedule. RESULTS: The children's mean age at initial US evaluation was 19 months; 71% were girls, and most (88%) had resided in orphanages. They were adopted from 16 countries, most frequently from China (48%) and Russia (31%). Thirty-five percent (178) of children had overseas immunization records, 167 (94%) of which were considered valid. Most children with valid records (112 [67%] of 167) were UTD for 1 or more vaccine series under the US schedule. CONCLUSION: The majority (65%) of internationally adopted children had no written records of overseas immunizations. Among the 178 children with documented overseas immunizations, 167 (94%) had valid records and some vaccine doses that were acceptable and UTD under the US schedule. Additional research and more specific guidance in the most cost-effective approaches to evaluation of overseas vaccinations are needed to ensure appropriate state-side vaccination and to improve the health of these children and their communities.

PMID: 11826232, UI: 21684080

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J Virol 2002 Mar;76(5):2100-12
 

Strong CD8 T-cell responses following coimmunization with plasmids expressing the dominant pp89 and subdominant M84 antigens of murine cytomegalovirus correlate with long-term protection against subsequent viral challenge.

Ye M, Morello CS, Spector DH

Molecular Biology Section, Division of Biology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0366, USA.

We previously showed that intradermal immunization with plasmids expressing the murine cytomegalovirus (MCMV) protein IE1-pp89 or M84 protects against viral challenge and that coimmunization has a synergistic protective effect (C. S. Morello, L. D. Cranmer, and D. H. Spector, J. Virol. 74:3696-3708, 2000). Using an intracellular gamma interferon cytokine staining assay, we have now characterized the CD8+ T-cell response after DNA immunization with pp89, M84, or pp89 plus M84. The pp89- and M84-specific CD8+ T-cell responses peaked rapidly after three immunizations. DNA immunization and MCMV infection generated similar levels of pp89-specific CD8+ T cells. In contrast, a significantly higher level of M84-specific CD8+ T cells was elicited by DNA immunization than by MCMV infection. Fusion of ubiquitin to pp89 enhanced the CD8+ T-cell response only under conditions where vaccination was suboptimal. Three immunizations with either pp89, M84, or pp89 plus M84 DNA also provided significant protection against MCMV infection for at least 6 months, with the best protection produced by coimmunization. A substantial percentage of antigen-specific CD8+ T cells remained detectable, and they responded rapidly to the MCMV challenge. These results underscore the importance of considering antigens that do not appear to be highly immunogenic during infection as DNA vaccine candidates.

PMID: 11836387, UI: 21826672

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J Virol 2002 Mar;76(5):2206-16
 

Safety and immunogenicity of ALVAC vCP1452 and recombinant gp160 in newly human immunodeficiency virus type 1-infected patients treated with prolonged highly active antiretroviral therapy.

Jin X, Ramanathan M Jr, Barsoum S, Deschenes GR, Ba L, Binley J, Schiller D, Bauer DE, Chen DC, Hurley A, Gebuhrer L, El Habib R, Caudrelier P, Klein M, Zhang L, Ho DD, Markowitz M

Aaron Diamond AIDS Research Center, The Rockefeller University, 455 1st Avenue, 7th Floor, New York, NY 10016, USA.

In order to boost immune responses in persons in whom highly active antiretroviral therapy (HAART) was initiated within 120 days of the onset of symptoms of newly acquired human immunodeficiency virus type 1 (HIV-1) infection, we administered vaccines containing a canarypox virus vector, vCP1452, with HIV-1 genes encoding multiple HIV-1 proteins, and recombinant gp160. Fifteen HIV-1-infected subjects who achieved sustained suppression of plasma viremia for at least 2 years were enrolled. While continuing antiretroviral therapy, each subject received at least four intramuscular injections of the vaccines on days 0, 30, 90, and 180. Adverse events were mild, with the most common being transient tenderness at the vCP1452 injection site. Of the 14 patients who completed vaccination, 13 had significant increases in anti-gp120 or anti-p24 antibody titers, and 9 had transient augmentation of their T-cell proliferation responses to gp160 and/or p24. HIV-1-specific CD8(+) T cells were quantified using an intracellular gamma interferon staining assay. Among 11 patients who had increased CD8(+) T-cell responses, seven had responses to more than one HIV-1 antigen. In summary, vaccination with vCP1452 and recombinant gp160 appears safe and immunogenic in newly HIV-1-infected patients on HAART.

Publication Types:
 

• Clinical trial

PMID: 11836398, UI: 21826683

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J Infect Dis 2002 Feb 15;185(4):489-96
 

Inhibition of pneumococcal carriage in mice by subcutaneous immunization with peptides from the common surface protein pneumococcal surface adhesin a.

Johnson SE, Dykes JK, Jue DL, Sampson JS, Carlone GM, Ades EW

Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Respiratory Diseases Branch, Atlanta, Georgia 30333, USA. sjohnson@cdc.gov

Pneumococcal surface adhesin A (PsaA), a common protein expressed on all 90 pneumococcal serotypes, is a vaccine candidate. Three anti-PsaA monoclonal antibody phage display-expressed monopeptides (15 mers), in various formulations as lipidated or nonlipidated multiantigenic peptides or as bi- or tripeptide constructs, were studied in a mouse nasopharyngeal carriage model to determine the inhibitory effect of induced antibodies on carriage of pneumococcal serotypes 2, 4, and 6B. Antibodies to each of the various peptides tested reduced carriage of the 3 serotypes. Reduction in carriage by nonlipidated multiantigenic peptide antibodies was highly variable (39%-94%; mean, 59%; standard deviation [SD], 20.2%); however, more-consistent results were observed in mice immunized with lipidated (56%-98%; mean, 69%; SD, 13.6%) and combination or bipeptide (55%-91%; mean, 76%; SD, 13.1%) formulations. These peptides are immunogenic, and their induced antibodies reduce carriage in mice. PsaA peptides demonstrate potential for being important new vaccines against pneumococcal carriage, otitis media, and invasive pneumococcal disease.

PMID: 11865401, UI: 21853521

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JAMA 2002 Mar 6;287(9):1104
 

From the World Health Organization.

Brundtland GH

PMID: 11879094, UI: 21872294

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JAMA 2002 Mar 6;287(9):1114-5
 

Molecular analysis of early postvaccine mumps-like disease in Italian military recruits.

Lista F, Faggioni G, Peragallo MS, Tontoli F, Stella A, Salvatori P, Pusino M, Germani MA, Contreas V, D'Amelio R

Publication Types:
 

• Letter

PMID: 11879107, UI: 21872307

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JAMA 2002 Mar 6;287(9):1107
 

From the Centers for Disease Control. Status of US Department of Defense preliminary evaluation of the association of anthrax vaccination and congenital anomalies.

PMID: 11885583, UI: 21881213

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JAMA 2002 Mar 13;287(10):1251-3
 

Sequencing of the malaria genome opens door to vaccines and new drugs.

Stephenson J

Publication Types:
 

• News

PMID: 11886299, UI: 21884275

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N Engl J Med 2002 Mar 14;346(11):864-6
 

Immunology series: vaccines.

Barton LL, Ada G

University of Arizona School of Medicine, Tucson, AZ 85724-5073, llb@peds.arizona.edu, Australian National University, ACT 2601 Canberra, Australia

[Medline record in process]
 

PMID: 11893804, UI: 21891042

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Infect Immun 2002 Apr;70(4):1739-49
 

Immune Responses to Recombinant Pneumococcal PspA Antigen Delivered by Live Attenuated Salmonella enterica Serovar Typhimurium Vaccine.

Kang HY, Srinivasan J, Curtiss R 3rd

Department of Biology, Washington University, St. Louis, Missouri 63130.

[Medline record in process]
 

Attenuated Salmonella enterica serovar Typhimurium expressing recombinant antigens from other pathogens elicits primarily a Th1-type dominant immune response to both recombinant and Salmonella antigens. The immunogenicity and appropriate subcellular location of the recombinant antigen in the Salmonella vaccine strain may contribute to augmenting immune responses by facilitating adequate exposure of recombinant antigen to antigen-presenting cells for processing. To allow for secretion from gram-negative bacteria and overexpression of antigen, a DNA fragment encoding a highly antigenic alpha-helical region of PspA (pneumococcal surface protein A) was subcloned downstream from the beta-lactamase signal sequence in the multicopy Asd(+) pYA3493 vector to create pYA3494. pYA3493 was derived from a class of Asd(+) vectors with reduced expression of Asd to minimize selective disadvantage and enhance immunization of expressed recombinant antigens. The S. enterica serovar Typhimurium vaccine strain was constructed by the introduction of deletion mutations Deltacrp-28 and DeltaasdA16. Approximately 50% of the recombinant PspA (rPspA) expressed in a Salmonella strain harboring pYA3494 was detected in the combined supernatant and periplasmic fractions of broth-grown recombinant SALMONELLA: After a single oral immunization in BALB/c mice with 10(9) CFU of the recombinant Salmonella vaccine strain carrying pYA3494, immunoglobulin G (IgG) antibody responses were stimulated to both the heterologous antigen rPspA and Salmonella lipopolysaccharide (LPS) and outer membrane proteins (OMPs). About half, and even more at later times after immunization, of the antibodies induced to rPspA were IgG1 (indicating a Th2-type response), whereas 60 to 70% of the antibodies to LPS and 80 to 90% of those to OMPs were IgG2a (indicating a Th1-type response). A sublethal infection with Streptococcus pneumoniae WU2 boosted PspA antibody levels and maintained IgG2a/IgG1 ratios similar to those seen before the challenge. Oral immunization with Salmonella-PspA vaccine protected 60% of immunized mice from death after intraperitoneal challenge with 50 times the 50% lethal dose of virulent S. pneumoniae WU2.

PMID: 11895935, UI: 21893083

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Infect Immun 2002 Apr;70(4):1874-1880
 

Safety and Immunogenicity of a Prototype Enterotoxigenic Escherichia coli Vaccine Administered Transcutaneously.

Guerena-Burgueno F, Hall ER, Taylor DN, Cassels FJ, Scott DA, Wolf MK, Roberts ZJ, Nesterova GV, Alving CR, Glenn GM

Department of Enteric Infections. Department of Clinical Trials. Department of Membrane Biochemistry, Walter Reed Army Institute of Research. Enteric Diseases Department, Naval Medical Research Center, Silver Spring, Maryland 20910-7500. IOMAI Corporation, Gaithersburg, Maryland 20878.

[Record supplied by publisher]
 

Transcutaneous immunization (TCI) is a new method for vaccine delivery that has been shown to induce immunity relevant to enteric disease vaccines. We evaluated the clinical safety and immunogenicity of a recombinant subunit vaccine against enterotoxigenic Escherichia coli (ETEC) delivered by TCI. Adult volunteers received patches containing the recombinant ETEC colonization factor CS6, either with heat-labile enterotoxin (LT) or patches containing CS6 alone. The vaccine was administered at 0, 1, and 3 months, and serum antibodies and antibody-secreting cells (ASCs) were assessed. Among the 26 volunteers that completed the trial, there were no responses to CS6 in the absence of LT. In the groups receiving both CS6 and LT, 68 and 53% were found to have serum anti-CS6 immunoglobulin G (IgG) and IgA, respectively; 37 and 42% had IgG and IgA anti-CS6 ASCs. All of the volunteers receiving LT had anti-LT IgG, and 90% had serum anti-LT IgA; 79 and 37% had anti-LT IgG and IgA ASCs. Delayed-type hypersensitivity (DTH), suggesting T-cell responses, was seen in 14 of 19 volunteers receiving LT and CS6; no DTH was seen in subjects receiving CS6 alone. This study demonstrated that protein antigens delivered by a simple patch could induce significant systemic immune responses but only in the presence of an adjuvant such as LT. The data suggest that an ETEC vaccine for travelers delivered by a patch may be a viable approach worthy of further evaluation.

PMID: 11895950

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Infect Immun 2002 Apr;70(4):1915-23
 

Yersinia enterocolitica as a Vehicle for a Naked DNA Vaccine Encoding Brucella abortus Bacterioferritin or P39 Antigen.

Al-Mariri A, Tibor A, Lestrate P, Mertens P, De Bolle X, Letesson JJ

Unite de Recherche en Biologie Moleculaire (URBM), Laboratoire d'Immunologie et de Microbiologie, Facultes Universitaires Notre-Dame de la Paix, B-5000 Namur, Belgium.

[Medline record in process]
 

Brucella is a facultative intracellular parasite that causes brucellosis in animals and humans. The protective immune response against Brucella involves both humoral and cell-mediated immunity. In previous studies, we demonstrated that the T-dominant Brucella antigens bacterioferritin (BFR) and P39 administered either as CpG adjuvant recombinant proteins or as naked-DNA plasmids induced a specific Th1-biased immune response in mice. In order to improve the protection conferred by the BFR and P39 vaccines and to evaluate the additive role of antilipopolysaccharide (anti-LPS) antibodies, we used live attenuated Yersinia enterocolitica serotypes O:3 and O:9 as delivery vectors for naked-DNA plasmids encoding these BFR and P39 antigens. Following two intragastric immunizations in BALB/c mice, the Yersinia vectors harboring a DNA vaccine encoding BFR or P39 induced antigen-specific serum immunoglobulin and Th1-type responses (both lymphocyte proliferation and gamma interferon production) among splenocytes. Moreover, as expected, antibodies recognizing Brucella abortus 544 lipopolysaccharide were detected in O:9-immunized mice but not in O:3-treated animals. Animals immunized with O:9 organisms carrying pCI or with O:9 organisms alone were found to be significantly resistant to infection by B. abortus 544. Our data demonstrated that pCI plasmids encoding BFR or P39 and delivered with live attenuated strains of Yersinia O:3 or O:9 can trigger Th1-type responses. The fact than only O:9 vectors induced a highly significant protective immunity against B. abortus 544 infection pointed out the crucial role of anti-LPS antibodies in protection. The best protection was conferred by a serotype O:9 strain carrying pCIP39, confirming the importance of the P39 T-cell antigen in this mechanism.

PMID: 11895955, UI: 21893103

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Infect Immun 2002 Apr;70(4):1949-1956
 

Coexpression of Interleukin-12 Chains by a Self-Splicing Vector Increases the Protective Cellular Immune Response of DNA and Mycobacterium bovis BCG Vaccines against Mycobacterium tuberculosis.

Palendira U, Kamath AT, Feng CG, Martin E, Chaplin PJ, Triccas JA, Britton WJ

Centenary Institute of Cancer Medicine and Cell Biology, Newtown, New South Wales 2042. Cooperative Research Center for Vaccine Technology, Queensland Institute of Medical Research, Queensland 4029. Department of Medicine, University of Sydney, New South Wales 2006, Australia. Bavarian Nordic Research Institute, Martinsried 82152, Germany.

[Record supplied by publisher]
 

More effective vaccines against Mycobacterium tuberculosis may contribute to the control of this major human pathogen. DNA vaccines encoding single mycobacterial proteins stimulate antimycobacterial T-cell responses and induce partial protection against M. tuberculosis in animal models. The protective efficacy of these vaccines encoding a single antigen, however, has been less than that afforded by the current vaccine, Mycobacterium bovis bacillus Calmette-Guerin (BCG). The heterodimeric cytokine interleukin-12 (IL-12) potentiates the induction and maintenance of the type 1 helper T-cell response. We have developed a novel self-splicing vector based on the 2A protein of foot-and-mouth disease virus that permits the coordinate expression of both chains of IL-12 (p2AIL12). Coimmunization with this vector and DNA expressing M. tuberculosis antigen 85B or MPT64 enhanced the specific lymphocyte proliferative response and increased the frequency of specific gamma interferon-secreting T cells against the whole protein and a defined CD8(+) T-cell epitope on MPT64. Further, coimmunizing with p2AIL12 significantly increased the protective efficacy of DNA-85 in the lung against an aerosol challenge with M. tuberculosis to the level achieved with BCG. Therefore, codelivery of an IL-12-secreting plasmid may be a potent strategy for enhancing the protective efficacy of vaccines against M. tuberculosis.

PMID: 11895958

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Infect Immun 2002 Apr;70(4):1965-1970
 

Randomized, Controlled Human Challenge Study of the Safety, Immunogenicity, and Protective Efficacy of a Single Dose of Peru-15, a Live Attenuated Oral Cholera Vaccine.

Cohen MB, Giannella RA, Bean J, Taylor DN, Parker S, Hoeper A, Wowk S, Hawkins J, Kochi SK, Schiff G, Killeen KP

Division of Pediatric Gastroenterology, Hepatology and Nutrition. Center for Epidemiology and Biostatistics. Gamble Program for Clinical Studies, Children's Hospital Medical Center. Digestive Diseases, University of Cincinnati and VA Medical Center, Cincinnati, Ohio. Walter Reed Army Institute of Research, Washington, D.C. AVANT Immunotherapeutics, Inc., Needham, Massachusetts.

[Record supplied by publisher]
 

Peru-15 is a live attenuated oral vaccine derived from a Vibrio cholerae O1 El Tor Inaba strain by a series of deletions and modifications, including deletion of the entire CT genetic element. Peru-15 is also a stable, motility-defective strain and is unable to recombine with homologous DNA. We wished to determine whether a single oral dose of Peru-15 was safe and immunogenic and whether it would provide significant protection against moderate and severe diarrhea in a randomized, double-blind, placebo-controlled human volunteer cholera challenge model. A total of 59 volunteers were randomly allocated to groups to receive either 2 x 10(8) CFU of reconstituted, lyophilized Peru-15 vaccine diluted in CeraVacx buffer or placebo (CeraVacx buffer alone). Approximately 3 months after vaccination, 36 of these volunteers were challenged with approximately 10(5) CFU of virulent V. cholerae O1 El Tor Inaba strain N16961, prepared from a standardized frozen inoculum. Among vaccinees, 98% showed at least a fourfold increase in vibriocidal antibody titers. After challenge, 5 (42%) of the 12 placebo recipients and none (0%) of the 24 vaccinees had moderate or severe diarrhea (>/=3,000 g of diarrheal stool) (P = 0.002; protective efficacy, 100%; lower one-sided 95% confidence limit, 75%). A total of 7 (58%) of the 12 placebo recipients and 1 (4%) of the 24 vaccinees had any diarrhea (P < 0.001; protective efficacy, 93%; lower one-sided 95% confidence limit, 62%). The total number of diarrheal stools, weight of diarrheal stools, incidence of fever, and peak stool V. cholerae excretion among vaccinees were all significantly lower than in placebo recipients. Peru-15 is a well-tolerated and immunogenic oral cholera vaccine that affords protective efficacy against life-threatening cholera diarrhea in a human volunteer challenge model. This vaccine may therefore be a safe and effective tool to prevent cholera in travelers and is a strong candidate for further evaluation to prevent cholera in an area where cholera is endemic.

PMID: 11895960

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Infect Immun 2002 Apr;70(4):2016-2021
 

Phase I Evaluation of DeltavirG Shigella sonnei Live, Attenuated, Oral Vaccine Strain WRSS1 in Healthy Adults.

Kotloff KL, Taylor DN, Sztein MB, Wasserman SS, Losonsky GA, Nataro JP, Venkatesan M, Hartman A, Picking WD, Katz DE, Campbell JD, Levine MM, Hale TL

Division of Infectious Disease and Tropical Pediatrics, Department of Pediatrics. Division of Geographic Medicine, Department of Medicine, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland 21201. Department of Enteric Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland 20307. Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045.

[Record supplied by publisher]
 

We conducted a phase I trial with healthy adults to evaluate WRSS1, a live, oral DeltavirG Shigella sonnei vaccine candidate. In a double-blind, randomized, dose-escalating fashion, inpatient volunteers received a single dose of either placebo (n = 7) or vaccine (n = 27) at 3 x 10(3) CFU (group 1), 3 x 10(4) CFU (group 2), 3 x 10(5) CFU (group 3), or 3 x 10(6) CFU (group 4). The vaccine was generally well tolerated, although a low-grade fever or mild diarrhea occurred in six (22%) of the vaccine recipients. WRSS1 was recovered from the stools of 50 to 100% of the vaccinees in each group. The geometric mean peak anti-lipopolysaccharide responses in groups 1 to 4, respectively, were 99, 39, 278, and 233 for immunoglobulin (IgA) antibody-secreting cell counts; 401, 201, 533, and 284 for serum reciprocal IgG titers; and 25, 3, 489, and 1,092 for fecal IgA reciprocal titers. Postvaccination increases in gamma interferon production in response to Shigella antigens occurred in some volunteers. We conclude that WRSS1 vaccine is remarkably immunogenic in doses ranging from 10(3) to 10(6) CFU but elicits clinical reactions that must be assessed in further volunteer trials.

PMID: 11895966

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Infect Immun 2002 Apr;70(4):2029-38
 

Construction of a tetR-Integrated Salmonella enterica Serovar Typhi CVD908 Strain That Tightly Controls Expression of the Major Merozoite Surface Protein of Plasmodium falciparum for Applications in Human Vaccine Production.

Qian F, Pan W

Department of Etiologic Biology, Second Military Medical University, Shanghai, China.

[Medline record in process]
 

Attenuated Salmonella strains are an attractive live vector for delivery of a foreign antigen to the human immune system. However, the problem with this vector lies with plasmid segregation and the low level of expression of the foreign gene in vivo when constitutive expression is employed, leading to a diminished immune response. We have established inducible expressions of foreign genes in the Salmonella enterica serovar Typhi CVD908 vaccine strain using the tetracycline response regulatory promoter. To set up this system, a tetracycline repressor (tetR) was integrated into a defined DeltaaroC locus of the chromosome via suicide plasmid pJG12/tetR-neo. To remove the neo gene conferring kanamycin resistance from the locus, a cre expression vector under the control of the tetracycline response promoter was transformed into the clone; expression of the Cre recombinase excised the neo gene and generated the end strain CVD908-tetR. Expression of the luciferase reporter gene in this strain is dependent on the presence of tetracycline in the medium and can be regulated up to 4,773-fold. Moreover, the tightly controlled expression of major merozoite surface protein 1 (MSP1) and parts of Plasmodium falciparum was achieved, and the product yield was increased when the inducible expression system was employed. Inoculation of bacteria harboring plasmid pZE11/MSP1(42) in mice produced the protein in liver and spleen controlled by the inducer. The persistence of the plasmid-carrying bacteria in mice was determined. Peak colonization of both liver and spleen was detected on the third day postinoculation and was followed by a decline in growth curves. After 14 days postinfection, the majority of the bacteria (>90%) recovered from the liver and spleen of the mice retained the plasmid when expression was induced; this clearly indicated that stability of the expression vector in vivo was improved by inducible expression. Establishment of the regulatory system in the vaccine strain may broaden the range of its use by enhancing plasmid stability and expression levels in vivo. Moreover, the availability of the vaccine strain inducibly expressing the entire MSP1 provides possibilities for examining its immunogenicity, particularly the cellular response in animal models.

PMID: 11895968, UI: 21893116

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Infect Immun 2002 Apr;70(4):2159-2165
 

Vaccination of Guinea Pigs with DNA Encoding the Mycobacterial Antigen MPB83 Influences Pulmonary Pathology but Not Hematogenous Spread following Aerogenic Infection with Mycobacterium bovis.

Chambers MA, Williams A, Hatch G, Gavier-Widen D, Hall G, Huygen K, Lowrie D, Marsh PD, Hewinson RG

TB Research Group, Department of Bacterial Diseases. Department of Pathology, Veterinary Laboratories Agency Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, Research Division. Pathology, CAMR, Salisbury, SP4 0JG, NIMR, Mill Hill, London, United Kingdom. Department of Virology, Pasteur Institute, B-1180 Brussels, Belgium.

[Record supplied by publisher]
 

Protection of cattle against bovine tuberculosis by vaccination could be an important control strategy in countries where there is persistent Mycobacterium bovis infection in wildlife and in developing countries where it is not economical to implement a tuberculin test and slaughter control program. The main aim of such a vaccination strategy would be to reduce transmission of infection by reducing the lung pathology caused by infection and preventing seeding of the organism to organs from which M. bovis could be excreted. Recent reports of successful DNA vaccination against Mycobacterium tuberculosis in small-animal models have suggested that DNA vaccines act by reducing lung pathology without sensitizing animals to tuberculin testing. We therefore evaluated the ability of vaccines consisting of DNA encoding the mycobacterial antigens MPB83 and 85A to reduce lung pathology and prevent hematogenous spread in guinea pigs challenged with a low dose of aerosolized M. bovis. Vaccination with MPB83 DNA reduced the severity of pulmonary lesions, as assessed by histopathology, and resembled M. bovis BCG vaccination in this respect. However, unlike BCG vaccination, MPB83 DNA vaccination did not protect challenged guinea pigs from hematogenous spread of organisms to the spleen. In contrast, vaccination with antigen 85A DNA, a promising DNA vaccine for human tuberculosis, had no measurable protective effect against infection with M. bovis.

PMID: 11895982

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Infect Immun 2002 Apr;70(4):2171-2177
 

Immunogenicity of a 26-Valent Group A Streptococcal Vaccine.

Hu MC, Walls MA, Stroop SD, Reddish MA, Beall B, Dale JB

ID Biomedical Corporation, Bothell, Washington. Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia. Department of Veterans Affairs Medical Center and Department of Medicine, University of Tennessee, Memphis, Tennessee.

[Record supplied by publisher]
 

A multivalent vaccine containing amino-terminal M protein fragments from 26 different serotypes of group A streptococci was constructed by recombinant techniques. The vaccine consisted of four different recombinant proteins that were formulated with alum to contain 400 &mgr;g of protein per dose. Rabbits were immunized via the intramuscular route at 0, 4, and 16 weeks. Immune sera were assayed for the presence of type-specific antibodies against the individual recombinant M peptides by enzyme-linked immunosorbent assay and for opsonic antibodies by in vitro opsonization tests and indirect bactericidal tests. The 26-valent vaccine was highly immunogenic and elicited fourfold or greater increases in antibody levels against 25 of the 26 serotypes represented in the vaccine. The immune sera were broadly opsonic and were bactericidal against the majority of the 26 different serotypes. Importantly, none of the immune sera cross-reacted with human tissues. Our results indicate that type-specific, protective M protein epitopes can be incorporated into complex, multivalent vaccines designed to elicit broadly protective opsonic antibodies in the absence of tissue-cross-reactive antibodies.

PMID: 11895984

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Science 2002 Mar 14;
 

Outbreak of Poliomyelitis in Hispaniola Associated with Circulating Type 1 Vaccine-Derived Poliovirus.

Kew O, Morris-Glasgow V, Landaverde M, Burns C, Shaw J, Garib Z, Andre J, Blackman E, Freeman CJ, Jorba J, Sutter R, Tambini G, Venczel L, Pedreira C, Laender F, Shimizu H, Yoneyama T, Miyamura T, van Der Avoort H, Oberste MS, Kilpatrick D, Cochi S, Pallansch M, de Quadros C

Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention (CDC), 1600 Clifton Road, Atlanta, GA 30333, USA., Caribbean Epidemiology Centre (CAREC) Laboratory, Pan American Health Organization (PAHO), 16-18 Jamaica Boulevard, Federation Park, Port-of-Spain, Trinidad and Tobago., Division of Vaccines and Immunization, PAHO, 525 Twenty-third Street, N.W., Washington, DC 20037, USA., Ministry of Health, Avenida San Cristobal esquina Tiradentes, Santo Domingo, Dominican Republic., Ministry of Public Health, Port-au-Prince, Haiti., Vaccine Preventable Disease Eradication Division, National Immunization Program, CDC, 1600 Clifton Road, Atlanta, GA 30333, USA., PAHO, Calle Pepillo Salcedo, Plaza de la Salud, Santo Domingo, Dominican Republic., PAHO, No. 295 Avenue John Brown, Port-au-Prince, Haiti., Department of Virology II, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162, Japan., Polio Laboratory, National Institute of Public Health and the Environment (RIVM), Antonie van Leeuwenhoeklaan 9, 3720 BA, Bilthoven, Netherlands.

[Record supplied by publisher]
 

An outbreak of paralytic poliomyelitis occurred in the Dominican Republic (13 confirmed cases) and Haiti (8 confirmed cases, including 2 fatal cases) during 2000-2001. All but one of the patients were either unvaccinated or incompletely vaccinated children, and cases occurred in communities with very low (7? to 40?) rates of coverage with oral poliovirus vaccine (OPV). The outbreak was associated with the circulation of a derivative of the type 1 OPV strain, probably originating from a single OPV dose given in 1998-1999. The vaccine-derived poliovirus associated with the outbreak had biological properties indistinguishable from those of wild poliovirus.

PMID: 11896235

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Science 2002 Mar 15;295(5562):1998-2001
 

Public health. U.S. vaccine supply falls seriously short.

Cohen J

[Medline record in process]
 

Publication Types:
 

• News

PMID: 11896251, UI: 21893762

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