Pediatric invasive pneumococcal disease caused by vaccine serotypes following the introduction of conjugate vaccination in Denmark.

A seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the Danish childhood immunization program (2+1 schedule) in October 2007, followed by PCV13 starting from April 2010. The nationwide incidence of IPD among children younger than 5 years nearly halved after the introduction of PCV7 in the program, mainly due to a decline in IPD caused by PCV7-serotypes. We report the results from a nationwide population-based cohort study of laboratory confirmed IPD cases in children younger than 5 years during October 1, 2007 to December 31, 2010 and describe the characteristics of children suspected to present with a vaccine failure.

Early-life and contemporaneous nutritional and environmental predictors of antibody response to vaccination in young Gambian adults.

Recent research links nutritional exposures early in life with alterations in functional immunity that persist beyond childhood. Here we investigate predictors of antibody response to polysaccharide vaccines in a cohort of Gambian adults with detailed records from birth and early infancy available. 320 adults were given a single dose of a Vi polysaccharide vaccine for Salmonella typhi and a 23-valent capsular polysaccharide pneumococcal vaccine.

Immunogenicity of a single dose of meningococcal group C conjugate vaccine given at 3 months of age to healthy infants in the United kingdom.

Background: From 1999, in the United Kingdom, meningococcal C conjugate (MCC) vaccines from 3 manufacturers were introduced to the infant immunization schedule at 2, 3 and 4 months of age. In 2006, the schedule was refined to a 2-dose primary schedule at 3 and 4 months of age, with a combined MCC/Haemophilus influenzae type b (MCC/Hib-TT) booster at 12 months of age. Recent data have demonstrated that 2 of the 3 MCC vaccines showed potential for use as a single priming dose in infancy.

Pneumococcal conjugate vaccine given shortly after birth stimulates effective antibody concentrations and primes immunological memory for sustained infant protection.

Background: In developing countries, newborn immunization with pneumococcal conjugate vaccines (PCVs) could protect young infants who are at high risk of invasive pneumococcal disease (IPD) but might lead to immune tolerance.

Methods: In a randomized trial, young infants received 7-valent PCV at 6, 10, and 14 weeks (Expanded Programme on Immunization [EPI] group) or 0, 10, and 14 weeks (newborn group). Safety was monitored actively at 2-7 days and then passively.

Comparison of a new multiplex binding assay versus the enzyme-linked immunosorbent assay for measurement of serotype-specific pneumococcal capsular polysaccharide IgG.

The measurement of serotype-specific anti-capsular polysaccharide antibodies remains the mainstay of pneumococcal (Pn) vaccine evaluation. New methods that allow the simultaneous measurement of antibodies to several antigens in small volumes of serum, and that agree well with existing techniques, are urgently required to support the increasing number of concomitant vaccines delivered in the infant immunization schedules and the use of extended-valency Pn vaccines. We therefore compared a relatively new multiplexed platform for measuring anti-Pn antibodies with the existing WHO consensus enzyme-linked immunosorbent assay (ELISA).

Safety and immunogenicity of coadministering a combined meningococcal serogroup C and Haemophilus influenzae type b conjugate vaccine with 7-valent pneumococcal conjugate vaccine and measles, mumps, and rubella vaccine at 12 months of age.

The coadministration of the combined meningococcal serogroup C conjugate (MCC)/Haemophilus influenzae type b (Hib) vaccine with pneumococcal conjugate vaccine (PCV7) and measles, mumps, and rubella (MMR) vaccine at 12 months of age was investigated to assess the safety and immunogenicity of this regimen compared with separate administration of the conjugate vaccines. Children were randomized to receive MCC/Hib vaccine alone followed 1 month later by PCV7 with MMR vaccine or to receive all three vaccines concomitantly. Immunogenicity endpoints were MCC serum bactericidal antibody (SBA) titers of ≥8, Hib-polyribosylribitol phosphate (PRP) IgG antibody concentrations of ≥0.

Multilaboratory comparison of Streptococcus pneumoniae opsonophagocytic killing assays and their level of agreement for the determination of functional antibody activity in human reference sera.

Antibody-mediated killing of Streptococcus pneumoniae (pneumococcus) by phagocytes is an important mechanism of protection of the human host against pneumococcal infections. Measurement of opsonophagocytic antibodies by use of a standardized opsonophagocytic assay (OPA) is important for the evaluation of candidate vaccines and required for the licensure of new pneumococcal conjugate vaccine formulations. We assessed agreement among six laboratories that used their own optimized OPAs on a panel of 16 human reference sera for 13 pneumococcal serotypes.

Circulating pneumococcal specific plasma and memory B cells in the elderly two years after pneumococcal conjugate versus polysaccharide vaccination.

Background: Polysaccharide conjugate vaccines prime for lasting memory responses in children and young adults. The potential value of these vaccines in the elderly is unclear.

Methods: We compared the frequency of circulating pneumococcal capsular polysaccharide (PPS) specific IgG, IgA and IgM plasma and memory cells by cultured ELISpot and supernatant screening two years after vaccination with the 7-valent pneumococcal conjugate vaccine (7vCRM) and/or the 23-valent pneumococcal polysaccharide vaccine (PPV) in 252 adults aged 50-80 years.

Immunogenicity of a reduced schedule of pneumococcal conjugate vaccine in healthy infants and correlates of protection for serotype 6B in the United Kingdom.

Background: Pneumococcal conjugate vaccine (PCV) was introduced in the United Kingdom immunization schedule in September 2006. This study was conducted to establish the immunogenicity of licensed PCV (Prevenar) at a reduced, 2 priming dose schedule (2+1) and to evaluate functional responses in the context of vaccine effectiveness.

Methods: Infants were randomized to receive PCV at 2 and 3 months or 2 and 4 months of age.

The immunogenicity of 7-valent pneumococcal conjugate vaccine versus 23-valent polysaccharide vaccine in adults aged 50-80 years.

Background: Infections with pneumococci are a major cause of morbidity and mortality in the elderly population. Although 23-valent pneumococcal polysaccharide vaccine (PPV) is recommended for elderly persons, the potential benefits of conjugate vaccine use in this age group remain unclear.

Methods: We performed an open-label, randomized study that compared 7-valent pneumococcal conjugate vaccine (7vPnC) with PPV in 599 adults aged 50-80 years.

Avidity of the immunoglobulin G response to a Neisseria meningitidis group C polysaccharide conjugate vaccine as measured by inhibition and chaotropic enzyme-linked immunosorbent assays.

Antibody avidity, the strength of the multivalent interaction between antibodies and their antigens, is an important characteristic of protective immune responses. We have developed an inhibition enzyme-linked immunosorbent assay (ELISA) to measure antibody avidity for the capsular polysaccharide (PS) of Neisseria meningitidis group C (MnC) and determined the avidity constants (K(D)s) for 100 sera from children immunized with an MnC PS conjugate vaccine. The avidity constants were compared to the avidity indices (AI) obtained for the same sera using a chaotropic ELISA protocol.

Immunogenicity and boosting after a reduced number of doses of a pneumococcal conjugate vaccine in infants and toddlers.

Background: The minimum number of doses of pneumococcal conjugate vaccine required for protection is not known. We studied the immunogenicity of a reduced schedule in infants and toddlers.

Methods: U.

Critical differences between pneumococcal polysaccharide enzyme-linked immunosorbent assays with and without 22F inhibition at low antibody concentrations in pediatric sera.

A comparative study was conducted between two laboratories in order to evaluate the differences between two enzyme-linked immunosorbent assay (ELISA) techniques for the detection of pneumococcal anti-capsular polysaccharide antibodies. One laboratory used an assay including heterologous 22F polysaccharide inhibition, and the other laboratory employed a non-22F reference assay. After conjugate immunization, 30 pediatric post-primary immunization sera with antipolysaccharide concentrations ranging from <0.

Antibody responses to nasopharyngeal carriage of Streptococcus pneumoniae in adults: a longitudinal household study.

Background: Natural immunity to Streptococcus pneumoniae is thought to be induced by exposure to S. pneumoniae or cross-reactive antigens. No longitudinal studies of carriage of and immune responses to S.

Effects of prior polysaccharide vaccination on magnitude, duration, and quality of immune responses to and safety profile of a meningococcal serogroup C tetanus toxoid conjugate vaccination in adults.

Extensive use of meningococcal AC polysaccharide (MACP) vaccines has raised concerns about induction of immunologic hyporesponsiveness to C polysaccharide. We investigated the immunogenicity and safety of a meningococcal C-tetanus conjugate (MCC-TT) vaccine in naive adults and prior MACP vaccinees. Laboratory staff (n = 113) were recruited; 73 were naive to meningococcal vaccination, and 40 had previously received > or =1 dose of MACP vaccine.

Immunogenicity of, and immunologic memory to, a reduced primary schedule of meningococcal C-tetanus toxoid conjugate vaccine in infants in the United kingdom.

It has been previously shown that one of the three meningococcal C conjugate (MCC) vaccines introduced in the United Kingdom proved highly immunogenic after the first dose of a three-dose schedule, with evidence of immune memory after dose 3. Thus, in infants a one- or two-dose schedule of this MCC vaccine, conjugated to tetanus toxoid (TT), may suffice. Healthy infants (n = 586) were randomized to receive either one (group 1), two (group 2), or three (group 3) doses of MCC-TT vaccine with a 10- micro g polysaccharide booster given at 13 to 14 months of age.

Antibody persistence and immunological memory at age 4 years after meningococcal group C conjugate vaccination in children in the United kingdom.

Antibody persistence and immunological priming for 2 formulations of a meningococcal group C (menC) conjugate (MCC) vaccine (containing 2 or 10 microg of menC polysaccharide) administered at 2, 3, and 4 months of age was investigated by boosting vaccine recipients at age 13-16 months or 4 years with 10 microg of unconjugated menC polysaccharide. At age 4 years, geometric mean titers (GMTs) and concentrations of menC-specific immunoglobulin G and serum bactericidal antibody (SBA) had decreased to prevaccination levels. Geometric mean avidity indices increased after the primary vaccination until age 13-16 months and then remained constant until age 4 years.