Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine (PCV15) in healthy infants.

Background: Pediatric use of pneumococcal conjugate vaccines (PCV) has been associated with significant decrease in disease burden. However, disease caused by non-vaccine serotypes has increased. Safety and immunogenicity of 15-valent PCV (PCV15) containing serotypes included in 13-valent PCV (PCV13) plus serotypes 22F and 33F were evaluated in infants (NCT01215188).

Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine in pneumococcal vaccine-naïve adults ≥50 years of age.

Background: Pneumococcal disease remains a public health priority in adults. Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine (PCV15) containing 13 serotypes included in 13-valent pneumococcal conjugate vaccine (PCV13) plus 2 additional serotypes (22F and 33F) was evaluated in adults ≥50 years old (NCT01513551).

Methods: 691 adults received one dose of PCV15, PCV13, or 23-valent pneumococcal polysaccharide vaccine (PPV23) and were followed 14 days for safety.

Vaccination of adults with 23-valent pneumococcal polysaccharide vaccine induces robust antibody responses against pneumococcal serotypes associated with serious clinical outcomes.

PNEUMOVAX™ 23, a 23-valent polysaccharide pneumococcal vaccine (PPV23), covers 65% to 91% of the isolates recovered from adult cases of invasive pneumococcal disease. Several studies have demonstrated that pneumococcal serotypes 31, 11A, 35F, 17F, 3, 16F, 19F, 15B, and 10A are associated with higher case-fatality or meningitis rates than other pneumococcal serotypes. This study (U05-PnPS-403; EudraCT: 2008-003648-12) evaluated the immune response followings administration of PPV23 for 4 of these serotypes (10A, 11A, 15B, and 17F), that are included in PPV23 but not in licensed pneumococcal conjugate vaccines.

Safety, tolerability, and immunogenicity of 15-valent pneumococcal conjugate vaccine in healthy adults.

Background: Pneumococcal disease remains an important health priority despite successful implementation of pneumococcal conjugate vaccines (PCVs) in infant immunization programs, mainly due to the emergence of diseases caused by serotypes not included in licensed PCVs. A 15-valent pneumococcal conjugate vaccine (PCV-15) containing the 7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) included in licensed PCV-7 available at study initiation plus 8 additional serotypes (1, 3, 5, 6A, 7F, 19A, 22F, 33F) was developed and evaluated in healthy adults 18-45 years of age.

Methods: Sixty subjects received one dose of PCV-15 or PCV-7.

Safety, tolerability and immunogenicity of 15-valent pneumococcal conjugate vaccine in toddlers previously vaccinated with 7-valent pneumococcal conjugate vaccine.

Background: Widespread use of 7-valent pneumococcal conjugate vaccine (PCV7) in children has led to significant reduction in pneumococcal disease in children and adults. However, diseases caused by serotypes not included in PCV7 have increased. A 15-valent pneumococcal conjugate vaccine (PCV15) containing serotypes in PCV7 and 8 additional serotypes (1, 3, 5, 6A, 7F, 19A, 22F, 33F) was developed and evaluated in toddlers 12 to 15 months of age.

Antibody persistence ten years after first and second doses of 23-valent pneumococcal polysaccharide vaccine, and immunogenicity and safety of second and third doses in older adults.

In a study of older adults, first and second doses of 23-valent pneumococcal polysaccharide vaccine (PN23) induced IgG increases for all 8 vaccine serotypes tested. Participants (N=143, mean age 76 years) were re-enrolled to study antibody levels after ten years, and safety and immunogenicity of another PN23 dose. Ten years after first or second doses, mean IgG concentrations exceeded vaccine-naïve levels for 7 of 8 serotypes tested.

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 antibody response, including antibody persistence for 5 years, after primary vaccination or revaccination with pneumococcal polysaccharide vaccine in middle-aged and older adults.

Background: This study assessed antibody levels for 5 years after primary vaccination or revaccination with 23-valent pneumococcal polysaccharide vaccine (PN23).

Methods: Subjects were enrolled into 4 study groups by age (50-64 or > or = 65 years) and prior vaccination status (no prior vaccination or 1 vaccination 3-5 years previously). Blood was obtained on day 0 (before primary vaccination or revaccination), day 30, day 60, and annually during years 2-5.

Revaccination with a 23-valent pneumococcal polysaccharide vaccine induces elevated and persistent functional antibody responses in adults aged 65 > or = years.

Background: Older adults are at high risk of developing invasive pneumococcal disease, but the optimal timing and number of vaccine doses needed to prevent disease among this group are unknown. We compared revaccination with 23-valent pneumococcal polysaccharide vaccine (PN23) with primary vaccination for eliciting initial and persistent functional antibody responses.

Methods: Subjects aged > or = 65 years were enrolled.

Varicella-zoster virus-specific immune responses to herpes zoster in elderly participants in a trial of a clinically effective zoster vaccine.

Background: The objectives of this study were to evaluate the association between varicella-zoster virus (VZV)-specific humoral and cell-mediated immunity (CMI) to herpes zoster (HZ) and protection against HZ morbidity and to compare immune responses to HZ and zoster vaccine.

Methods: In 981 elderly persons who developed HZ during a zoster vaccine efficacy trial (321 vaccinees and 660 placebo recipients) and 1362 without HZ (682 vaccinees and 680 placebo recipients), CMI was measured by VZV responder cell frequency and interferon-gamma enzyme-linked immunospot, and antibodies were measured by VZV enzyme-linked immunosorbent assay against affinity-purified VZV glycoproteins (gpELISA).

Results: Robust VZV CMI at HZ onset correlated with reduced HZ morbidity, whereas VZV gpELISA titers did not.

Optimization and validation of a multiplex, electrochemiluminescence-based detection assay for the quantitation of immunoglobulin G serotype-specific antipneumococcal antibodies in human serum.

Pneumovax 23 consists of a mixture of highly purified capsular polysaccharides (Ps) from 23 of the most prevalent serotypes of Streptococcus pneumoniae. Testing of vaccine immunogenicity has been historically performed on the enzyme-linked immunosorbent assay (ELISA) platform, validated to measure immunoglobulin G (IgG) antibodies to all 23 serotypes included in Pneumovax 23. In order to significantly improve the throughput of this form of testing, we have developed and validated a direct binding electrochemiluminescence (ECL)-based multiplex assay that can measure the antibody response in human serum to eight serotypes within a single microtiter well.

Complexities of clinical assay development and optimization prior to first-in-man immunization trials - a description of immunogenicity assay development for the testing of samples from a phase 1 Alzheimer's vaccine trial.

Immunogenicity is often a critical clinical endpoint in the assessment of vaccines prior to the submission of data to regulatory agencies. As a result, the assays used to measure immunogenicity must be highly characterized, well-controlled, and statistically supported. These goals are not easily attained, however, when the development of the assay must occur prior to the first-in-man studies.

The optimization and validation of the glycoprotein ELISA assay for quantitative varicella-zoster virus (VZV) antibody detection.

Varicella is a highly contagious viral disease found throughout the world. A live-attenuated Varicella-Zoster virus (VZV) vaccine (Oka/Merck strain), VARIVAXtrade mark, was licensed in the United States (US) in 1995 and was made a part of the US recommended childhood vaccination schedule in 1996. The immune response to VZV-containing vaccines has been measured using an enzyme-linked immunosorbent assay (ELISA) to detect antibodies to glycoproteins from VZV.

Enzyme-linked immunosorbent assay for measuring antibodies to pneumococcal polysaccharides for the PNEUMOVAX 23 vaccine: assay operating characteristics and correlation to the WHO international assay.

The Merck pneumococcal (Pn) enzyme-linked immunosorbent assays (ELISAs) for measuring antibodies to 12 serotypes (serotypes 1, 3, 4, 6B, 7F, 8, 9V, 12F, 14, 18C, 19F, and 23F) were validated in 1999. Merck Laboratories developed the Pn assays using 10 microg/ml C polysaccharide, 100 microg/ml Pn polysaccharide (PnPs) 25, and 100 microg/ml PnPs 72 for preadsorption of samples, standards, and controls in order to improve the specificity to the Pn serotypes in the vaccine. The Pn assays utilize postimmunization sera obtained from subjects immunized with PNEUMOVAX 23 as standards for measuring immunoglobulin G concentrations in sera obtained from vaccine clinical trials with adults and infants.

Memory T cells and vaccines.

T lymphocytes play a central role in the generation of a protective immune response in many microbial infections. After immunization, dendritic cells take up microbial antigens and traffic to draining lymph nodes where they present processed antigens to naïve T cells. These naïve T cells are stimulated to proliferate and differentiate into effector and memory T cells.