Paul Balmer

The Impact of 7-valent Pneumococcal Conjugate Vaccine on Invasive Pneumococcal Disease: A Literature Review

IntroductionStreptococcus pneumoniae can cause invasive pneumococcal diseases (IPD), such as bacteremic pneumonia, bacteremia, meningitis, and sepsis, and non-IPDs, such as otitis media, nonbacteremic pneumonia, and upper respiratory tract infections. It was estimated in 2000 that, worldwide, S. pneumoniae was responsible for 826,000 deaths annually in children aged between 1 month and 5 years. A 7-valent pneumococcal conjugate vaccine (PCV7) was licensed in 2000 in the USA and in 2001 in Europe.MethodsA literature search was performed in PubMed to identify studies assessing the impact of routine childhood PCV7 vaccination on pneumococcal morbidity and mortality. Here, the impact on IPD is reported.ResultsA total of 37 articles reporting impact data on IPD were included in this review: four from Australia, 17 from western Europe, and 16 from North America. In vaccine-eligible children in the postvaccination period, a reduction ranging from 39.9% in Spain to 99.1% in the USA in vaccine-type (VT) IPD incidence, compared with the prevaccination period, was reported in 18 studies. All but one of the 30 studies assessing the impact of PCV7 on all-type IPD reported a reduction ranging from 1.7% in Spain to 76.3% in Australia. In addition, the majority of studies reported reductions in VT and all-type IPD incidence in age groups that were not vaccine eligible.ConclusionsThe results from this review illustrate that PCV7 has had a significant impact on IPD across all ages through its use in pediatric immunization programs. With the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) further reductions in the incidence of IPD due to the six additional serotypes included, as well as continued protection against IPD due to PCV7 serotypes may be expected. Robust surveillance systems are essential for the evaluation of the impact of PCV13 on all-type IPD and for monitoring the evolution of non-VT IPD.

Characteristics of a new meningococcal serogroup B vaccine, bivalent rLP2086 (MenB-FHbp; Trumenba®)

ABSTRACT Neisseria meningitidis is a common cause of bacterial meningitis, often leading to permanent sequelae or death. N. meningitidis is classified into serogroups based on the composition of the bacterial capsular polysaccharide; the 6 major disease-causing serogroups are designated A, B, C, W, X, and Y. Four of the 6 disease-causing serogroups (A, C, Y, and W) can be effectively prevented with available quadrivalent capsular polysaccharide protein conjugate vaccines; however, capsular polysaccharide conjugate vaccines are not effective against meningococcal serogroup B (MnB). There is no vaccine available for serogroup X. The public health need for an effective serogroup B vaccine is evident, as MnB is the most common cause of meningococcal disease in the United States and is responsible for almost half of all cases in persons aged 17 to 22 years. In fact, serogroup B meningococci were responsible for the recent meningococcal disease outbreaks on college campuses. However, development of a suitable serogroup B vaccine has been challenging, as serogroup B polysaccharide-based vaccines were found to be poorly immunogenic. Vaccine development for MnB focused on identifying potential outer membrane protein targets that elicit broadly protective immune responses across strains from the vast number of proteins that exist on the bacterial surface. Human factor H binding protein (fHBP; also known as LP2086), a conserved surface-exposed bacterial lipoprotein, was identified as a promising vaccine candidate. Two recombinant protein-based serogroup B vaccines that contain fHBP have been successfully developed and licensed in the United States under an accelerated approval process: bivalent rLP2086 (MenB-FHbp; Trumenba®) and 4CMenB (MenB-4 C; Bexsero®). This review will focus on bivalent rLP2086 only, including vaccine components, mechanism of action, and potential coverage across serogroup B strains in the United States.

History of Meningococcal Outbreaks in the United States: Implications for Vaccination and Disease Prevention

Invasive meningococcal disease caused by Neisseria meningitidis presents a significant public health concern. Meningococcal disease is rare but potentially fatal within 24 hours of onset of illness, and survivors may experience permanent sequelae. This review presents the epidemiology, incidence, and outbreak data for invasive meningococcal disease in the United States since 1970, and it highlights recent changes in vaccine recommendations to prevent meningococcal disease. Relevant publications were obtained by database searches for articles published between January 1970 and July 2015. The incidence of meningococcal disease has decreased in the United States since 1970, but serogroup B meningococcal disease is responsible for an increasing proportion of disease burden in young adults. Recent serogroup B outbreaks on college campuses warrant broader age‐based recommendations for meningococcal group B vaccines, similar to the currently recommended quadrivalent vaccine that protects against serogroups A, C, W, and Y. After the recent approval of two serogroup B vaccines, the Advisory Committee on Immunization Practices first updated its recommendations for routine meningococcal vaccination to cover at‐risk populations, including those at risk during serogroup B outbreaks, and later it issued a recommendation for those aged 16–23 years. Meningococcal disease outbreaks remain challenging to predict, making the optimal disease management strategy one of prevention through vaccination rather than containment. How the epidemiology of serogroup B disease and prevention of outbreaks will be affected by the new category B recommendation for serogroup B vaccines remains to be seen.

PCVs in individuals at increased risk of pneumococcal disease: a literature review

The use of pneumococcal conjugate vaccine (PCV) in childhood pneumococcal immunization programs successfully reduced the incidence of pneumococcal disease in children. Nonetheless, there remains a high burden of pneumococcal disease in adults, especially the elderly, and children/adults with chronic medical conditions. Two pneumococcal vaccines are currently available for adults at risk of pneumococcal disease: the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the more recently licensed PCV13. As it is not possible to determine vaccine efficacy in all populations at risk of pneumococcal disease, immunogenicity studies, measuring pneumococcal-specific antibody concentrations and/or the opsonophagocytic activity of serum can provide valuable comparative data for PPV and PCV immunization. This article provides consolidated data on the immunogenicity of PCVs (largely PCV7, and a few studies with PCV9 or PCV13) based on a review of immunogenicity/safety studies in populations (mainly pediatric) at increased risk of pneumococcal disease.

Impact of meningococcal vaccination on carriage and disease transmission: A review of the literature

ABSTRACT Colonization of the human nasopharyngeal tract by the bacterium Neisseria meningitidis is usually asymptomatic, but life-threatening meningococcal disease with a clinical presentation of meningitis, septicemia, or more rarely, gastrointestinal symptoms, can develop. Invasive meningococcal disease (IMD) can be fatal within 24 hours, but IMD is vaccine-preventable. Vaccines used to protect against IMD caused by 5 of the 6 most common serogroups (A, B, C, W, and Y) may also influence carriage prevalence in vaccinated individuals. Lower carriage among vaccinated people may reduce transmission to nonvaccinated individuals to provide herd protection against IMD. This article reviews observational and clinical studies examining effects of vaccination on N. meningitidis carriage prevalence in the context of mass vaccination campaigns and routine immunization programs. Challenges associated with carriage studies are presented alongside considerations for design of future studies to assess the impact of vaccination on carriage.

Letter to the editor: Importance of serum bactericidal activity for estimating the breadth of protection for new meningococcal vaccines

To the editor: Brehony and colleagues [1] recently reported their investigation of six Neisseria meningitidis serogroup B (NmB) vaccines by deducing the prevalence of the vaccine components in isolates represented in publicly accessible sequence repositories of NmB. Based on the frequency of exact match of deduced peptide sequences in the databases to at least one component of each vaccine, and by assessing published data, the authors estimated the breadth of strain coverage. Their findings led them to conclude that meningococcal vaccines with multiple antigens would provide greater breadth of coverage against meningococcal disease. However, their evaluation did not incorporate important information about the diversity of factor H binding protein (fHBP) variants and the demonstration of protective immune responses against antigenically diverse MnB invasive disease strains following vaccination with Trumenba. Consequently, the authors’ analysis underestimates the potential for vaccine benefit provided by this licensed vaccine. We provide here a description of published data, including results that use the recognised correlate of protection for NmB, serum bactericidal activity measured using serum bactericidal assays performed with human complement (hSBA) [2,3]. This correlation was first validated in large clinical studies using outer membrane vesicle (OMV) vaccines that confer protection via induction of immune response directed against the PorA antigen of NmB [4]. Protection is essentially restricted to strains expressing the matched PorA sequence in the vaccine [5], thus the approach used by the authors to estimate vaccine strain coverage is appropriate for PorA based vaccines, such as the experimental vaccine NonaMen, as described.

Clinical data supporting a 2-dose schedule of MenB-FHbp, a bivalent meningococcal serogroup B vaccine, in adolescents and young adults

Invasive meningococcal disease (IMD) caused by Neisseria meningitidis is a potentially devastating condition that can result in death and is associated with serious long-term sequelae in survivors. Vaccination is the preferred preventative strategy. Quadrivalent polysaccharide-based vaccines that protect against infection caused by meningococcal serogroups A, C, W, and Y are not effective against meningococcal serogroup B (MenB), which was responsible for approximately 60% and 35% of confirmed IMD cases in the European Union and the United States in 2016, respectively. A recombinant protein MenB vaccine (MenB-FHbp [bivalent rLP2086; Trumenba®]) has been approved for protection against MenB infection in persons 10-25 years of age in the United States and Canada and for individuals ≥10 years of age in the European Union and Australia. In these regions, MenB-FHbp is approved as a 2- or 3-dose primary vaccination schedule. This report will review the current evidence supporting administration of MenB-FHbp as a 2-dose primary vaccination schedule. Different contexts in which a 2- or 3-dose primary vaccination schedule might be preferred (eg, routine prospective vaccination vs outbreak control) are reviewed.

Optimal use of meningococcal serogroup B vaccines: moving beyond outbreak control:

Neisseria meningitidis is a major cause of meningitis and septicemia globally. Vaccines directed against N. meningitidis serogroup B (MenB) have been used to control sporadic and sustained disease in industrialized and non-industrialized countries. Early outer membrane vesicle (OMV) vaccines effectively reduced MenB disease in countries such as Norway, New Zealand, and France; however, these vaccines were highly specific for their targeted outbreak strain, did not elicit a durable immune response, and were ineffective for widespread use due to the diversity of MenB-disease-causing isolates. Recently developed recombinant protein-based MenB vaccines that target conserved surface proteins have the potential to induce a broader immune response against the diversity of disease-causing strains. Given the deleterious consequences and sporadic nature of MenB disease, the use of optimal vaccination strategies is crucial for prevention. Reactive vaccination strategies used in the past have significant limitations, including delayed implementation, substantial use of resources, and time constraints. The broad coverage potential of recombinant protein-based MenB vaccines suggests that routine use could result in a reduced burden of disease. Despite this, routine use of MenB vaccines is currently limited in practice.

Meningococcal Group A, C, W, and Y Tetanus Toxoid Conjugate Vaccine: A Review of Clinical Data in Adolescents

MenACWY-TT (Nimenrix) is a quadrivalent meningococcal vaccine containing polysaccharides from serogroups A, C, W, and Y conjugated to a tetanus toxoid carrier protein. MenACWY-TT is licensed in some countries as a three-dose primary series in individuals as young as 6 weeks of age and as a single dose in individuals ≥12 months of age. MenACWY-TT use is supported by long-term immunogenicity and safety across age groups, including data from several phase 2, 3, and 4 clinical studies in adolescents and young adults. Adolescents are an important population in the epidemiology, transmission, and prevention of invasive meningococcal disease, with this age-based population having the highest risk for carriage and transmission as well as one of the highest risks of disease. This age group is emerging as a target population in meningococcal vaccination programs globally, as vaccinating adolescents and young adults could potentially not only decrease disease rates directly for those vaccinated but also indirectly for unvaccinated individuals by decreasing carriage and eliciting herd protection. This review will consider available data for MenACWY-TT in adolescents, including safety and immunogenicity, booster and memory responses, persistence, and coadministration with other vaccines, with an emphasis on the rationale for use of MenACWY-TT and other quadrivalent meningococcal vaccines in adolescents to address the changing epidemiology of meningococcal disease.

A Review of Meningococcal Disease and Vaccination Recommendations for Travelers

AbstractInternational travel has been steadily increasing since the middle of the twentieth century, including travel to regions with high levels of endemic meningococcal disease and areas with sporadic or sustained meningococcal outbreaks. Although invasive meningococcal disease (IMD) is relatively rare in travelers since the advent of quadrivalent meningococcal vaccines, it remains a serious concern because of its rapid progression, poor prognosis and outcomes, associated treatment delays, and the potential to precipitate outbreaks. Moreover, fatality occurs in up to 22% of those infected. This review will focus on IMD in travelers, with an emphasis on IMD epidemiology and the geographic regions of potential concern for international travelers. As vaccination is the best approach for preventing IMD among travelers, currently available meningococcal vaccines and corresponding country-specific national meningococcal vaccination recommendations, where available, will be summarized by age and type of vaccine recommended. The use of the quadrivalent meningococcal vaccines, specifically the tetanus toxoid conjugate vaccine (including MenACWY-TT; Nimenrix®), as a protective measure against IMD in travelers will be emphasized.FundingPfizer Inc.