Resolution of Chlamydia trachomatis Infection Is Associated with a Distinct T Cell Response Profile.

Chlamydia trachomatis is the causative agent of the most frequently reported bacterial sexually transmitted infection, the total burden of which is underestimated due to the asymptomatic nature of the infection. Untreated C. trachomatis infections can cause significant morbidities, including pelvic inflammatory disease and tubal factor infertility (TFI).

Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian children in the second year of life.

Unlabelled: Rotavirus gastroenteritis is one of the leading causes of diarrhea in Indian children less than 2 years of age. The 116E rotavirus strain was developed as part of the Indo-US Vaccine Action Program and has undergone efficacy trials. This paper reports the efficacy and additional safety data in children up to 2 years of age.

Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: a randomised, double-blind, placebo-controlled trial.

Background: Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed in these countries. We aimed to assess the efficacy and tolerability of a monovalent human-bovine rotavirus vaccine for severe rotavirus gastroenteritis in low-resource urban and rural settings in India.

Evaluation of safety and immunogenicity of recombinant influenza hemagglutinin (H5/Indonesia/05/2005) formulated with and without a stable oil-in-water emulsion containing glucopyranosyl-lipid A (SE+GLA) adjuvant.

Background: Expression of recombinant hemagglutinin (rHA) in insect cells represents a technology with proven efficacy in seasonal influenza and with the potential for a rapid response to the emergence of new, pandemic strains. We evaluated the safety and immunogenicity of rHA vaccine (H5/Indonesia/5/05) produced in SF+ insect cells using a baculovirus expression vector system (BEVS). The rHA vaccine was tested with and without the adjuvant glucopyranosyl lipid A/stable emulsion (GLA/SE).

Anthrax vaccine-induced antibodies provide cross-species prediction of survival to aerosol challenge.

Because clinical trials to assess the efficacy of vaccines against anthrax are not ethical or feasible, licensure for new anthrax vaccines will likely involve the Food and Drug Administration's "Animal Rule," a set of regulations that allow approval of products based on efficacy data only in animals combined with immunogenicity and safety data in animals and humans. U.S.

Economic burden of acute lower respiratory tract infection in South African children.

Background: Acute lower respiratory tract infections (ALRTI) are a leading cause of childhood mortality, but there are few data on disease costs in developing countries.

Objectives: This study's purpose was to analyse ALRTI's costs-of-illness and economic burden in urban South African children.

Methods: ALRTI costs-of-illness (expressed in US$ 2010) at a tertiary hospital were measured using a micro-costing approach nested within a clinical trial.

Protective efficacy of a trivalent recombinant hemagglutinin protein vaccine (FluBlok®) against influenza in healthy adults: a randomized, placebo-controlled trial.

Background: Development of influenza vaccines that do not use embryonated eggs as the substrate for vaccine production is a high priority. We conducted this study to determine the protective efficacy a recombinant, baculovirus-expressed seasonal trivalent influenza virus hemagglutinin (rHA0) vaccine (FluBlok(®)).

Methods: Healthy adult subjects at 24 centers across the US were randomly assigned to receive a single injection of saline placebo (2304 subjects), or trivalent FluBlok containing 45 mcg of each rHA0 component (2344 subjects).

Predictive models and correlates of protection for testing biodefence vaccines.

The identification of immune correlates of protection is becoming increasingly important in order to derive a quantitative assessment of the benefit conferred by vaccination in clinical trials. The use of immune correlates of protection as an indirect measure of clinical efficacy is essential to achieve regulatory approval for vaccines for which clinical efficacy cannot be tested directly, for example, biodefence vaccines. The correlates apply to the specific vaccine formulation being developed; in general, if a statistically significant correlation is found between a measurable immunological readout and survival in authentic animal models of human infection, the same immunological readout can be defined and applied as a surrogate marker of protection in clinical studies.

Immunogenicity and serotype-specific efficacy of a 9-valent pneumococcal conjugate vaccine (PCV-9) determined during an efficacy trial in The Gambia.

This study aimed to determine the immunogenicity of a 9-valent pneumococcal conjugate vaccine (PCV-9) in a subgroup of Gambian children enrolled in a large vaccine efficacy trial. To place the antibody results in context, in this paper we also report previously unpublished data on serotype-specific clinical vaccine efficacy from the main trial. In the sub-study, a single 2-4 ml venous blood specimen was collected from 212 Gambian children 4-6 weeks after the administration of a third dose of PCV-9 or placebo.

Prediction of pertussis vaccine efficacy using a correlates of protection model.

A previously developed statistical model relates vaccine immune responses to protection against pertussis disease in a household contact setting. Before this model can be used to predict the risk of disease based on immune responses, it must be validated to demonstrate reliable predictions. The model is shown here to be validated in terms of statistical criteria (Prentice surrogacy measures) as well as predictive capability in an independent efficacy trial (meta-analysis).

Predictors of pneumococcal conjugate vaccine immunogenicity among infants and toddlers in an American Indian PnCRM7 efficacy trial.

Background: Pneumococcal conjugate vaccines are important for the prevention of serious illness and death among infants. Factors associated with pneumococcal conjugate vaccine immunogenicity have not been explored.

Methods: Children <24 months of age received 2, 3, or 4 doses of 7-valent pneumococcal conjugate vaccine (PnCRM7) or control vaccine depending on age at enrollment.

Estimating the protective concentration of anti-pneumococcal capsular polysaccharide antibodies.

Estimates of minimum protective antibody concentrations for vaccine preventable diseases are of critical importance in assessing whether new vaccines will be as effective as those for which clinical efficacy was shown directly. We describe a method for correlating pneumococcal anticapsular antibody responses of infants immunized with pneumococcal conjugate (PnC) vaccine (Prevenar) with clinical protection from invasive pneumococcal disease (IPD). Data from three double blind controlled trials in Northern Californian, American Indian and South African infants were pooled in a meta-analysis to derive a protective concentration of 0.

Design of vaccine equivalence/non-inferiority trials with correlated multiple binomial endpoints.

Immunogenicity trials that study the immune responses to vaccination are often used in the vaccine development process as alternatives to clinical efficacy trials. The comparisons of immune responses among various treatment groups are conducted in a non-inferiority or equivalence framework. When there exists a level of immune response that correlates with protection against disease, it is of interest to compare the proportion of responders as defined as response above a specific level or as a predefined increase in immune levels for post-vaccination levels above pre-vaccination levels.

Safety, efficacy, and immunogenicity of 2 doses of bovine-human (UK) and rhesus-rhesus-human rotavirus reassortant tetravalent vaccines in Finnish children.

Background: Live oral rhesus-rhesus-human rotavirus reassortant tetravalent (RRV-TV) vaccine was efficacious against rotavirus gastroenteritis but was withdrawn because of a rare association with intussusception. A corresponding tetravalent (types G1, G2, G3, and G4) reassortant vaccine based on bovine-human (UK) rotavirus reassortant tetravalent (BRV-TV) vaccine was developed concurrently.

Methods: Before the withdrawal of RRV-TV vaccine, parallel placebo-controlled trials of BRV-TV vaccine (observer blinded) versus RRV-TV vaccine (double blinded) with a 2 : 1 ratio of vaccine : placebo were conducted in Finland in a total of 510 infants.

Serum serotype-specific pneumococcal anticapsular immunoglobulin g concentrations after immunization with a 9-valent conjugate pneumococcal vaccine correlate with nasopharyngeal acquisition of pneumococcus.

Background: Immunization with pneumococcal conjugate vaccines (PCVs) reduces nasopharyngeal colonization by Streptococcus pneumoniae. We attempted to correlate postvaccination serum serotype-specific pneumococcal anticapsular immunoglobulin (Ig) G concentrations with new acquisitions of vaccine-type (VT) serotypes and the VT-related serotype 6A.

Methods: A total of 132 day care center attendees aged 12-35 months received a 9-valent PCV (PnCRM9) and were followed for 2 years for new nasopharyngeal acquisitions of S.

Type I error and power in noninferiority/equivalence trials with correlated multiple endpoints: an example from vaccine development trials.

Clinical trials necessary for the development of new treatment often require testing of multiple endpoints for equivalence or noninferiority relative to an existing effective standard therapy. An example is a vaccine study with multiple antibody measurements in sera of subjects receiving a combination vaccine such as a pneumococcal vaccine, which contains many different serotypes of the pneumococcal organism. This article describes testing methods for the demonstration of simultaneous marginal equivalence or noninferiority of two treatments on each component of the response vector that follows a multivariate normal distribution.

A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection.

Background: Acute respiratory tract infections caused by Streptococcus pneumoniae are a leading cause of morbidity and mortality in young children. We evaluated the efficacy of a 9-valent pneumococcal conjugate vaccine in a randomized, double-blind study in Soweto, South Africa.

Methods: At 6, 10, and 14 weeks of age, 19,922 children received the 9-valent pneumococcal polysaccharide vaccine conjugated to a noncatalytic cross-reacting mutant of diphtheria toxin (CRM197), and 19,914 received placebo.

Efficacy and safety of seven-valent conjugate pneumococcal vaccine in American Indian children: group randomised trial.

Background: Streptococcus pneumoniae is the main cause of invasive bacterial disease in children aged younger than 2 years. Navajo and White Mountain Apache children have some of the highest rates of invasive pneumococcal disease documented in the world. We aimed to assess the safety and efficacy of a seven-valent polysaccharide protein conjugate pneumococcal vaccine (PnCRM7) against such disease.

Serological criteria for evaluation and licensure of new pneumococcal conjugate vaccine formulations for use in infants.

The World Health Organization (WHO) is undertaking a series of consultations on serological criteria for the evaluation and licensure of new formulations/combinations or different vaccination schedules of pneumococcal conjugate vaccines. The lack of a definitive serological correlate of protection and the multiplicity of antigens involved, especially since the clinical efficacy of most of the individual serotypes represented in the only licensed vaccine has not been established, are hindering the formulation of criteria for licensure of new formulations or combinations of the vaccine. This report analyses the various options with their relative merits and drawbacks and provides preliminary recommendations as guidance to regulatory agencies in evaluating these vaccines for the purposes of licensure.

Design of a group-randomized Streptococcus pneumoniae vaccine trial.

A group-randomized, double-masked, phase III trial of a Streptococcus pneumoniae conjugate vaccine is being conducted in American Indian populations in the southwestern United States. Approximately 9000 infants will be enrolled in the primary efficacy cohort with vaccine allocation determined by community of residence. The trial is designed to continue until 48 cases of invasive pneumococcal disease due to vaccine serotypes have accumulated.

Efficacy of a pneumococcal conjugate vaccine against acute otitis media.

Background: Ear infections are a common cause of illness during the first two years of life. New conjugate vaccines may be able to prevent a substantial portion of cases of acute otitis media caused by Streptococcus pneumoniae.

Methods: We enrolled 1662 infants in a randomized, double-blind efficacy trial of a heptavalent pneumococcal polysaccharide conjugate vaccine in which the carrier protein is the nontoxic diphtheria-toxin analogue CRM197.

Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group.

Objective: To determine the efficacy, safety and immunogenicity of the heptavalent CRM197 pneumococcal conjugate vaccine against invasive disease caused by vaccine serotypes and to determine the effectiveness of this vaccine against clinical episodes of otitis media.

Methods: The Wyeth Lederle Heptavalent CRM197 (PCV) was given to infants at 2, 4, 6 and 12 to 15 months of age in a double blind trial; 37,868 children were randomly assigned 1:1 to receive either the pneumococcal conjugate vaccine or meningococcus type C CRM197 conjugate. The primary study outcome was invasive disease caused by vaccine serotype.

Safety and immunogenicity of heptavalent pneumococcal CRM197 conjugate vaccine in infants and toddlers.

Objectives: The objectives of this study were (1) to determine the safety and immunogenicity of heptavalent pneumococcal CRM197 conjugate (PNCRM7) vaccine in infants and (2) to determine the effect of concurrent hepatitis B immunization during the primary series and the effect of concurrent diphtheria and tetanus toxoid and acellular pertussis [DTaP (ACEL-IMUNE)] and conjugate CRM197 Haemophilus influenzae type b [HbOC (HibTITER) immunization at time of the booster dose on the safety and immunogenicity of PNCRM7and these other concurrently administered vaccines.

Methods: This was a randomized double-blinded study in 302 healthy infants in the Northern California Kaiser Permanente (NCKP) Health Plan. Infants received either PNCRM7 vaccine or meningococcal group C conjugate vaccine as a control at 2, 4 and 6 months of age and a booster at 12 to 15 months of age.

Morphometric measurements and RNA content of axotomized feline cervical motoneurons.

Microspectrophotometric estimates of RNA content and morphometric measurements of cytoplasmic, nuclear and nucleolar areas were made on 30 to 60 motoneurons (somal areas greater than 1000 microns2) ipsilateral and contralateral to brachial plexotomy performed unilaterally on adult cats 2-90 days before sacrifice. Nerve cells of unoperated animals were also assayed. Somal and cytoplasmic areas of axotomized motoneurons were larger than those of the corresponding, contralateral motor nerve cells 4, 6 and 75 days postoperatively.