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J Infect Dis 2002 Oct 15;186(8):1065-73
 

Prime-boost immunization with DNA and modified vaccinia virus ankara vectors expressing herpes simplex virus-2 glycoprotein d elicits greater specific antibody and cytokine responses than DNA vaccine alone.

Meseda CA, Elkins KL, Merchlinsky MJ, Weir JP

Laboratory of DNA Viruses, Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA.

[Medline record in process]
 

Several reports have indicated that prime-boost strategies of vaccination can enhance the level of specific immunity induced by nucleic acid vaccines. The present report describes such a strategy with herpes simplex virus (HSV)-2 glycoprotein D (gD), using combinations of plasmid vector that expresses gD (pgD2) and a recombinant modified vaccinia virus Ankara vector that expresses gD (MVA-gD2). The IgG antibody response to gD and the HSV-2 neutralizing antibody response were greatest when the MVA-gD2 vector was used as the priming immunization and then was boosted with either pgD2 or MVA-gD2. Determination of the isotype profile of MVA-gD2-primed mice revealed a much broader distribution of isotypes than that seen after DNA vaccination. In addition, antigen-stimulated spleen cells from mice primed with MVA-gD2 and boosted with either MVA-gD2 or pgD2 produced higher levels of interleukin-2 and interferon-gamma than did those from pgD2-primed mice, indicating that a prime-boost immunization strategy that uses the MVA and plasmid DNA vector dramatically enhances and diversifies the humoral and cellular immune response to HSV-2 gD.

PMID: 12355355, UI: 22242166

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J Virol 2002 Sep;76(18):9176-85
 

Induction of immune responses in mice and monkeys to Ebola virus after immunization with liposome-encapsulated irradiated Ebola virus: protection in mice requires CD4(+) T cells.

Rao M, Bray M, Alving CR, Jahrling P, Matyas GR

Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500, USA. Mangala.Rao@Na.Amedd.Army.Mil

Ebola Zaire virus (EBO-Z) causes severe hemorrhagic fever in humans, with a high mortality rate. It is thought that a vaccine against EBO-Z may have to induce both humoral and cell-mediated immune responses to successfully confer protection. Because it is known that liposome-encapsulated antigens induce both antibody and cellular responses, we evaluated the protective efficacy of liposome-encapsulated irradiated EBO-Z [L(EV)], which contains all of the native EBO-Z proteins. In a series of experiments, mice immunized intravenously with L(EV) were completely protected (94/94 mice) against illness and death when they were challenged with a uniformly lethal mouse-adapted variant of EBO-Z. In contrast, only 55% of mice immunized intravenously with nonencapsulated irradiated virus (EV) survived challenge, and all became ill. Treatment with anti-CD4 antibodies before or during immunization with L(EV) eliminated protection, while treatment with anti-CD8 antibodies had no effect, thus indicating a requirement for CD4(+) T lymphocytes for successful immunization. On the other hand, treatment with either anti-CD4 or anti-CD8 antibodies after immunization did not abolish the protection. After immunization with L(EV), antigen-specific gamma interferon (IFN gamma)-secreting CD4(+) T lymphocytes were induced as analyzed by enzyme-linked immunospot assay. Anti-CD4 monoclonal antibody treatment abolished IFN gamma production (80 to 90% inhibition compared to that for untreated mice). Mice immunized with L(EV), but not EV, developed cytotoxic T lymphocytes specific to two peptides (amino acids [aa] 161 to 169 and aa 231 to 239) present in the amino-terminal end of the EBO-Z surface glycoprotein. Because of the highly successful results in the mouse model, L(EV) was also tested in three cynomolgus monkeys. Although immunization of the monkeys with L(EV)-induced virus-neutralizing antibodies against EBO-Z caused a slight delay in the onset of illness, it did not prevent death.

PMID: 12186901, UI: 22174907

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J Virol 2002 Sep;76(18):9002-10
 

The immunogenicity and protective efficacy of bovine herpesvirus 1 glycoprotein D plus Emulsigen are increased by formulation with CpG oligodeoxynucleotides.

Ioannou XP, Griebel P, Hecker R, Babiuk LA, van Drunen Littel-van den Hurk S

Veterinary Infectious Disease Organization, Saskatoon, Saskatchewan, S7N 5E3 Canada.

The immunogenicity and protective efficacy of a bovine herpesvirus 1 (BHV-1) subunit vaccine formulated with Emulsigen (Em) and a synthetic oligodeoxynucleotide containing unmethylated CpG dinucleotides (CpG ODN) was determined in cattle. A truncated, secreted version of BHV-1 glycoprotein D (tgD) formulated with Em and CpG ODN at concentrations of 25, 2.5, or 0.25 mg/dose produced a more balanced immune response, higher levels of virus neutralizing antibodies, and greater protection after BHV-1 challenge compared to tgD adjuvanted with either Em or CpG ODN alone. In contrast, tgD formulated with Em and either 25 mg of a non-CpG ODN or another immunostimulatory compound, dimethyl dioctadecyl ammonium bromide, induced similar immunity and protection compared to tgD formulated with Em alone, a finding which confirms the immunostimulatory effect of ODN to be CpG motif mediated. Our results demonstrate the ability of CpG ODN to induce a strong and balanced immune response in a target species.

PMID: 12186884, UI: 22174890

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Lancet 2002 Sep 21;360(9337):953
 

Positive effect of meningococcal C vaccination on serogroup replacement in Neisseria meningitidis.

Perez-Trallero E, Vicente D, Montes M, Cisterna R

Servicio de Microbiologi;a, Basque Country Reference Laboratory for Meningococcal Infections, Hospital Donostia, 20014 San Sebastian, Gipuzkoa, Spain

[Medline record in process]
 

PMID: 12354504, UI: 22242445

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Lancet 2002 Sep 7;360(9335):804
 

Congenital rubella: down but not out.

Nardone A, Gay NJ, Edmunds WJ

Publication Types:
 

• Comment
• Letter

PMID: 12241854, UI: 22227222

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Pediatrics 2002 Oct;110(4):841-5
 

Smallpox vaccine.

[Medline record in process]
 

After an extensive worldwide eradication program, the last nonlaboratory case of smallpox occurred in 1977 in Somalia. In 1972, routine smallpox immunization was discontinued in the United States, and since 1983, vaccine production has been halted. Stockpiled vaccine has been used only for laboratory researchers working on orthopoxviruses. In recent years, there has been concern that smallpox virus stocks may be in the hands of bioterrorists, and this concern has been heightened by the terrorist attack on the World Trade Center and the Pentagon on September 11, 2001. Because most of the population is considered to be nonimmune, there is debate as to whether smallpox immunization should be resumed. This statement reviews the current status of smallpox vaccine, the adverse effects that were associated with smallpox vaccine in the past, and the major proposals for vaccine use. The statement provides the rationale for a policy based on the so-called ring vaccination strategy recommended by the Centers for Disease Control and Prevention, in which cases of smallpox are rapidly identified, infected individuals are isolated, and contacts of the infected individuals as well as their contacts are immunized immediately.

PMID: 12359807, UI: 22247540

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Pediatrics 2002 Oct;110(4):805-14
 

The future of pneumococcal conjugate vaccines for prevention of pneumococcal diseases in infants and children.

Pelton SI, Klein JO

Department of Pediatrics, Boston University School of Medicine, and Department of Pediatrics, Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center, Boston, Massachusetts.

[Medline record in process]
 

Seven-valent pneumococcal conjugate vaccine (PCV7) was licensed in February 2000. In June 2000, the Advisory Committee on Immunization Practices and the American Academy of Pediatrics recommended the universal administration of pneumococcal conjugate vaccine for all children 23 months of age and younger and for children 24 to 59 months of age who are at high risk for serious pneumococcal disease. Since then, >23 million doses have been administered in the United States. Postlicensure surveillance of invasive pneumococcal disease (IPD) in the United States from the Active Bacterial Core Surveillance program at the Centers for Disease Control and Prevention and the Northern California Kaiser Permanente Vaccine Study Center has reported a decline in IPD and in pneumococcal disease incidence as a result of vaccine serotypes, respectively. During this period, issues critical to the long-term success of PCV7 have become more relevant: Will PCV7 be as effective in groups of children who are at high risk for IPD as in healthy children? Will nonvaccine types replace vaccine serotypes in the nasopharynx and in disease? Why are the results of the clinical trials different for IPD and for acute otitis media? How many doses of PCV7 and what concentrations of antibody are necessary for protection? Will universal administration of PCV7 to children younger than 2 years reduce antimicrobial drug resistance and alter prescribing patterns of physicians for febrile infants? Have there been unanticipated adverse events or benefits observed? The purpose of this report is to review the current data available to address these questions and to identify gaps that will require additional knowledge to determine the ultimate value of pneumococcal conjugate vaccines in reducing the burden of pneumococcal disease in infants and children.

PMID: 12359799, UI: 22247532

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Pediatrics 2002 Oct;110(4):662-72
 

Safety of the trivalent, cold-adapted influenza vaccine in preschool-aged children.

Piedra PA, Yan L, Kotloff K, Zangwill K, Bernstein DI, King J, Treanor J, Munoz F, Wolff M, Cho I, Mendelman PM, Cordova J, Belshe RB

Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA. ppiedra@bcm.tmc.edu

[Medline record in process]
 

OBJECTIVE: To provide additional information on the safety of trivalent, cold-adapted influenza vaccine (CAIV-T) in children. METHODS: Children 15 to 71 months of age were enrolled in a multicenter, prospective, randomized, double-blind, and placebo-controlled trial to receive by nasal spray CAIV-T or placebo. In year 1 (1996-1997), 1314 were enrolled in the 2-dose cohort and 288 were enrolled in the 1-dose cohort. In year 2 (1997-1998), 1358 of the original participants received 1 dose of vaccine or placebo according to their original treatment group assignment. In year 3 (1998-1999) and year 4, the trial continued as an open-label safety trial of CAIV-T. A total of 642 and 549 children enrolled in years 3 and 4, respectively, received their third and fourth sequential annual doses of CAIV-T. Measured were 1) the occurrence of specific respiratory, gastrointestinal and systemic symptoms, unexpected symptoms (not specified in the diary card), and use of medications within the first 10 days after vaccination; 2) the occurrence of an acute illness and use of medication within 11 to 42 days after vaccination; and 3) the occurrence of serious adverse events within 42 days after vaccination. RESULTS: The adjusted odd ratios of specific respiratory and gastrointestinal symptoms during the 10 days after vaccination were determined in years 1 and 2. Runny nose or nasal congestion, vomiting, muscle aches, and fever were significantly associated with the first dose of CAIV-T. With the second dose, runny nose was the only symptom that was associated with CAIV-T. In year 2, CAIV-T did not cause excess in any of the specific respiratory and gastrointestinal symptoms. In years 3 and 4, specific respiratory and gastrointestinal symptoms were comparable to that observed in year 2. A CAIV-T-associated symptom was most likely to occur on day 2 with the first dose of vaccine. The occurrence of unexpected symptoms was primarily of the gastrointestinal system. Approximately 6% of CAIV-T and 3.6% of placebo recipients had a gastrointestinal symptom. CAIV-T seemed to be associated with a mild excess in abdominal pain and vomiting only with the first vaccine dose. A statistically significant increase in the use of analgesics/antipyretics was detected only with the first dose in CAIV-T vaccinees compared with placebo recipients (23.5% vs 16.6%). Between days 11 and 42, CAIV-T use was not associated with an excess of illness, otitis media, or use of medication. None of the 6 serious adverse events in CAIV-T recipients in years 1 to 4 was attributed to the vaccine. CONCLUSIONS: CAIV-T was safe in children. Mild respiratory, gastrointestinal, and systemic symptoms of short duration were observed in a minority of children and primarily with the first vaccine dose. Sequential annual doses of CAIV-T were well tolerated.

PMID: 12359778, UI: 22247511

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Pediatrics 2002 Oct;110(4):653-61
 

Impact of Universal Haemophilus influenzae Type b Vaccination Starting at 2 Months of Age in the United States: An Economic Analysis.

Zhou F, Bisgard KM, Yusuf HR, Deuson RR, Bath SK, Murphy TV

National Immunization Program, Centers for Disease Control and Prevention, Public Health Service, US Department of Health and Human Services, Atlanta, Georgia.

[Medline record in process]
 

OBJECTIVE: To evaluate the economic impact of universal Haemophilus influenzae type b (Hib) vaccination starting at 2 months of age. METHODS: Decision-tree-based analysis was conducted of a hypothetical US birth cohort of 3 815 469 infants using population-based vaccination coverage and disease incidence data. All costs were estimated from both the direct cost (medical and nonmedical) and societal perspectives. Net present value, cost-effectiveness ratios, and benefit-cost ratios of the US Hib vaccination program were evaluated. RESULTS: The results of these analyses showed that the universal vaccination program using the Hib conjugate vaccines in the United States in 2000 was cost-saving from both the direct and societal perspectives, with the benefit of the Hib vaccination program (net present value) from the direct cost and societal perspectives of $0.95 billion and $2.09 billion, respectively. Without a Hib vaccination program, the direct and societal costs of Hib invasive cases would be $1.35 billion and $2.58 billion, respectively. The direct and societal costs of the Hib vaccination program were estimated at $0.39 billion and $0.48 billion, respectively. The direct and societal benefit-cost ratios for the Hib vaccination program were 3.4 and 5.4, respectively. Varying the proportion of vaccines purchased and administered in the public versus the private sector and the proportion of combination vaccine versus monovalent vaccine administered did not have much effect on the results. CONCLUSIONS: Regardless of the perspective (direct cost or societal) and the assumptions used, the benefit-cost ratios of the US vaccination program are >1.0. Potential changes in the program, including use of more or less Hib combination vaccines, would not significantly alter the benefit-cost ratio. The national Hib vaccination program is highly cost beneficial and results in substantial cost savings.

PMID: 12359777, UI: 22247510

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Wkly Epidemiol Rec 2002 Aug 30;77(35):290-4
 

Progress towards poliomyelitis eradication. Angola, January 1998-June 2002.

PMID: 12227256, UI: 22215238

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Wkly Epidemiol Rec 2002 Aug 2;77(31):257-64
 

Cholera, 2001.

PMID: 12189690, UI: 22177669

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