Adult indication 13-valent pneumococcal conjugate vaccine clinical development overview: formulation, safety, immunogenicity (dosing and sequence), coadministration, and efficacy.

Introduction: There was no 13-valent pneumococcal conjugate vaccine (PCV13) adult antibody concentration threshold regulatory criterion for licensure - unlike the pediatric indication; consequently, for the adult indication, PCV13 serotype-specific opsonophagocytic activity (OPA) geometric mean titer (GMT) values were immunobridged to the 23-valent plain polysaccharide vaccine (PPV23) to infer efficacy against invasive pneumococcal disease (IPD). Subsequently, a double-blind, randomized, controlled PCV13 efficacy trial (CAPiTA) was performed in community-living, older adults to confirm efficacy against vaccine-serotype IPD (VT-IPD) and establish efficacy against vaccine-serotype pneumococcal community-acquired pneumonia (VT-CAP).

Areas Covered: This article summarizes 31 publications from the PCV13 adult indication clinical development trials and other PCV13 clinical studies, organized by formulation, reactogenicity and safety, immunogenicity, coadministration, and clinical efficacy.

Pneumococcal conjugate vaccine in adults: Let's see what happens.

The recent recommendation for the use of the 13-valent pneumococcal conjugate vaccine (PCV13) in adults 65 y of age and older, provides a new tool for preventing disease in this at-risk population. The conjugate vaccine induces a T-cell dependent response, which distinguishes it from the polysaccharide vaccine and could provide the longer-term protection necessary to have a significant impact in this population.

Pneumococcal conjugate vaccine use in adults.

Streptococcus pneumoniae is a leading cause of illness and death in adults. A polysaccharide vaccine has been available for over 30 years, but despite significant use, the public health impact of this vaccine has been limited. The 13-valent pneumococcal conjugate vaccine (PCV13) has been licensed by the US Food and Drug Administration and other international regulatory authorities with the assumption that induction of a T cell-dependent immune response and noninferior immunogenicity to vaccine antigens when compared with the polysaccharide vaccine would be important to satisfy a significant unmet medical need.

Distribution of 13-valent pneumococcal conjugate vaccine Streptococcus pneumoniae serotypes in US adults aged ≥50 years with community-acquired pneumonia.

Background: Streptococcus pneumoniae causes a substantial proportion of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) in the United States. Limited data are available regarding the pneumococcal serotypes causing CAP and HCAP.

Methods: Adults aged ≥ 50 years presenting to participating US hospitals with radiographically confirmed pneumonia between February 2010 and September 2011 were screened for inclusion.

Immune response to 13-valent pneumococcal conjugate vaccine with a reduced dosing schedule.

Background: The 7-valent pneumococcal conjugate vaccine (PCV7) has demonstrated effectiveness against pneumococcal illnesses when administered as 3 infant doses plus a toddler dose (3+1 schedule) or as an abbreviated schedule of 2 infant doses plus a toddler dose (2+1 schedule). The 13-valent pneumococcal conjugate vaccine (PCV13) is approved and World Health Organization-prequalified for administration in a 2+1 schedule when used as part of routine immunization programs.

Objective: To summarize immunologic responses elicited by PCV13 administered in a 2+1 schedule and following 2 doses in a 3+1 schedule.

Pneumococcal conjugate vaccine for adults: a new paradigm.

A 13-valent pneumococcal conjugate vaccine has been studied in adults aged ≥ 50 years to compare the immune response to that induced by the 23-valent pneumococcal polysaccharide vaccine, which has been the standard of care over the past 30 years. The results demonstrate that adults, regardless of whether they are naive or previously vaccinated with the polysaccharide vaccine, have an overall superior antibody response when vaccinated with the conjugate vaccine compared with the pneumococcal polysaccharide vaccine. More importantly, the nature of the response is indicative of a T-cell-dependent response that elicits immunological memory and, therefore, primes the immune system for either natural exposure or subsequent booster vaccination with either conjugate or polysaccharide vaccine.

Advances in pneumococcal disease prevention: 13-valent pneumococcal conjugate vaccine for infants and children.

A 13-valent pneumococcal conjugate vaccine (PCV13), developed with the same chemistry used for the 7-valent PCV vaccine (PCV7) and with the goal of expanding serotype coverage, was clinically evaluated in the United States and Europe and found to induce capsular-specific antibody responses comparable to those of PCV7 for the common serotypes, with robust responses to the 6 additional serotypes. In addition, PCV13 has a similar safety profile to PCV7 and can be given routinely to infants and children, ideally as a 3-dose primary series in the first year of life, with a booster dose in the second year. Children who have initiated their vaccination program with PCV7 can transition to PCV13 at any point in the schedule.

Essential criteria for evaluation of pneumococcal conjugate vaccine candidates.

In 2003, the World Health Organization recommended a concentration of enzyme-linked immunosorbent assay (ELISA) immunoglobulin G (IgG) anti-capsular antibody of 0.35 microg/mL as a reference value that correlates to protection against invasive pneumococcal disease. This threshold can be used to demonstrate immunologic non-inferiority of a new vaccine in comparison trials that use pneumococcal conjugate vaccines (PCVs) as a comparator.

Immunology of combining CRM(197) conjugates for Streptococcus pneumoniae, Neisseria meningitis and Haemophilus influenzae in Chilean infants.

We evaluated the immunogenicity and safety of an investigational combination of 9-valent pneumococcal conjugate vaccine (PCV9) and meningococcal group C conjugate (MnCC) vaccine (PCV9-MnCC) administered concomitantly with Haemophilus influenzae type b (Hib) conjugate vaccine, and of a combination of the three vaccines mixed together as a single injection (Hib-PCV9-MnCC), and compared them to separately administered PCV9 and MnCC dispensed to Chilean infants at 2, 4, and 6 months of age. The frequency of adverse events was similar among groups. Recipients of PCV9 alone or in combination with the other vaccines mounted significant antibody responses to the nine pneumococcal serotypes in PCV9, with >88% achieving protective levels of > or =0.

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.

Establishing government-operated vaccine programs: an industry perspective.

During 2000-2002, shortages of numerous routinely administered pediatric vaccines occurred. The reasons for these shortages were varied, but they included policy, manufacturing, and regulatory issues. The use of government manufacturing programs has been proposed as a way to stabilize the fragile vaccine supply and to prevent periodic shortages.

Strengthening the supply of routinely recommended vaccines in the United States: recommendations from the National Vaccine Advisory Committee.

Between late 2000 and the spring of 2003, the United States experienced shortages of vaccines against 8 of 11 preventable diseases in children. In response, the Department of Health and Human Services requested that the National Vaccine Advisory Committee (NVAC) make recommendations on strengthening the supply of routinely recommended vaccines. The NVAC appointed a Working Group to identify potential causes of vaccine supply shortages, develop strategies to alleviate or prevent shortages, and enlist stakeholders to consider the applicability and feasibility of these strategies.

Recent progress in the development of vaccines for infants and children.

Infectious agents do not respect national or international boundaries. Attempts to prevent their spread, and the diseases which they cause, involve implementing vaccination as widely and as appropriately as possible. The principles of vaccination against infectious agents are now being applied to cancer and other non-infectious conditions.