Establishing a new human pneumococcal standard reference serum, MPRSS-01.

Measuring the immunogenicity of pneumococcal vaccines involves the use of immunoassays to measure serotype-specific immunoglobulin G (IgG) antibody levels post-vaccination with the current human reference serum standard (007sp) for anti-pneumococcal capsule antibodies. Development of new pneumococcal conjugate vaccines (PCVs) with additional serotypes not in 007sp (e.g.

Qualification of a 21-valent pneumococcal urine antigen detection assay and development of clinical positivity cutoffs.

Serotype-specific assays detecting pneumococcal polysaccharides in bodily fluids are needed to understand the pneumococcal serotype distribution in non-bacteremic pneumonia. We developed a urine antigen detection assay and using urine samples from adult outpatients without pneumonia developed positivity cutoffs for both a previously published 15-valent and the new 21-valent assay. Clinical sensitivity was confirmed with samples from patients with invasive pneumococcal disease.

A novel immuno-molecular strategy for the detection of Streptococcus pneumoniae serotypes in human cerebrospinal and middle ear fluids.

Streptococcus pneumoniae is one of the most common microorganisms causing acute otitis media (AOM) in children. While bacterial culture of middle ear fluid (MEF) is the gold standard to detect the etiological organisms, several host and pathogen factors impact the survival of the organisms resulting in false negatives. To overcome this limitation, we have developed and validated an innovative multiplex immuno-molecular assay to screen and detect the S.

Development and Validation of a Sensitive and Robust Multiplex Antigen Capture Assay to Quantify Streptococcus pneumoniae Serotype-Specific Capsular Polysaccharides in Urine.

Streptococcus pneumoniae is a major cause of community-acquired pneumonia (CAP) in young children, older adults, and those with immunocompromised status. Since the introduction of pneumococcal vaccines, the burden of invasive pneumococcal disease caused by vaccine serotypes (STs) has decreased; however, the effect on the burden of CAP is unclear, potentially due to the lack of testing for pneumococcal STs. We describe the development, qualification, and clinical validation of a high-throughput and multiplex ST-specific urine antigen detection (SSUAD) assay to address the unmet need in CAP pneumococcal epidemiology.

Diagnosis of Streptococcus pneumoniae infection using circulating antibody secreting cells.

Background: Streptococcus pneumoniae infections cause morbidity and mortality worldwide. A rapid, simple diagnostic method could reduce the time needed to introduce definitive therapy potentially improving patient outcomes.

Methods: We introduce two new methods for diagnosing S.

Effect of maternal Tdap on infant antibody response to a primary vaccination series with whole cell pertussis vaccine in São Paulo, Brazil.

Background: Maternal Tetanus, diphtheria, and acellular pertussis (Tdap) vaccination provides antibody transfer to newborn infants and may affect their antibody response to the primary vaccination series. This study aimed to assess the effect of Tdap vaccination during pregnancy on infant antibody response to the whole cell pertussis (DTwP) primary series.

Methods: Plasma from 318 pregnant women (243 Tdap-vaccinated and 75 unvaccinated) and their infants (cord blood) was collected at delivery; infant blood was again collected at 2 and 7 months, before and after their primary DTwP series.

Kinetics of maternal pertussis-specific antibodies in infants of mothers vaccinated with tetanus, diphtheria and acellular pertussis (Tdap) during pregnancy.

Background: Kinetics of Tdap-induced maternally-derived antibodies in infants are poorly understood. Pre-Tdap era data suggest that maternal pertussis antibodies in infants have a half-life of approximately 5-6 weeks.

Methods: 34 mother-infant pairs had blood collected before maternal Tdap vaccination, 4 weeks later, at delivery (maternal and cord), and at infant ages 3 and 6 weeks from June 2014-March 2015.

Late effects of total body irradiation on hematopoietic recovery and immune function in rhesus macaques.

While exposure to radiation can be lifesaving in certain settings, it can also potentially result in long-lasting adverse effects, particularly to hematopoietic and immune cells. This study investigated hematopoietic recovery and immune function in rhesus macaques Cross-sectionally (at a single time point) 2 to 5 years after exposure to a single large dose (6.5 to 8.

, and Strains With Highly Similar Loci and Antigenic Relatedness to Serotype 5 Pneumococci.

is a highly impactful bacterial pathogen on a global scale. The principal pneumococcal virulence factor and target of effective vaccines is its polysaccharide capsule, of which there are many structurally distinct forms. Here, we describe four distinct strains of three Mitis group commensal species (, , and ) recovered from upper respiratory tract specimens from adults in Kenya and the United States that were PCR-positive for the pneumococcal serotype 5 specific gene, .

Genetic Meningococcal Antigen Typing System (gMATS): A genotyping tool that predicts 4CMenB strain coverage worldwide.

Background: The Meningococcal Antigen Typing System (MATS) was developed to identify meningococcus group B strains with a high likelihood of being covered by the 4CMenB vaccine, but is limited by the requirement for viable isolates from culture-confirmed cases. We examined if antigen genotyping could complement MATS in predicting strain coverage by the 4CMenB vaccine.

Methods: From a panel of 3912 MATS-typed invasive meningococcal disease isolates collected in England and Wales in 2007-2008, 2014-2015 and 2015-2016, and in 16 other countries in 2000-2015, 3481 isolates were also characterized by antigen genotyping.

Streptococcus mitis Expressing Pneumococcal Serotype 1 Capsule.

Streptococcus pneumoniae's polysaccharide capsule is an important virulence factor; vaccine-induced immunity to specific capsular polysaccharide effectively prevents disease. Serotype 1 S. pneumoniae is rarely found in healthy persons, but is highly invasive and a common cause of meningitis outbreaks and invasive disease outside of the United States.

Development and validation of a robust multiplex serological assay to quantify antibodies specific to pertussis antigens.

Despite wide spread vaccination, the public health burden of pertussis remains substantial. Current acellular pertussis vaccines comprise upto five Bordetella pertussis (Bp) antigens. Performing an ELISA to quantify antibody for each antigen is laborious and challenging to apply to pediatric samples where serum volume may be limited.

Impact of maternally derived pertussis antibody titers on infant whole-cell pertussis vaccine response in a low income setting.

Background: Maternal vaccines against pertussis are not yet recommended in the developing world. Besides unclear burden estimates, another concern is that transplacental transfer of maternal pertussis antibodies could result in attenuation of the immune response to whole cell pertussis (DTwP) primary vaccination series in infants. This study was taken up to determine whether higher levels of maternal pertussis antibodies attenuate immune response of infants to DTwP vaccination series given at 6-10-14 weeks of age.

Meningococcal Antigen Typing System (MATS)-Based Serogroup B Coverage Prediction for the MenB-4C Vaccine in the United States.

is the most common cause of bacterial meningitis in children and young adults worldwide. A 4-component vaccine against serogroup B (MenB) disease (MenB-4C [Bexsero]; GSK) combining factor H binding protein (fHBP), neisserial heparin binding protein (NHBA), neisserial adhesin A (NadA), and PorA-containing outer membrane vesicles was recently approved for use in the United States and other countries worldwide. Because the public health impact of MenB-4C in the United States is unclear, we used the meningococcal antigen typing system (MATS) to assess the strain coverage in a panel of strains representative of serogroup B (NmB) disease in the United States.

Augmented Passive Immunotherapy with P4 Peptide Improves Phagocyte Activity in Severe Sepsis.

Introduction: Antimicrobial resistance threatens to undermine treatment of severe infection; new therapeutic strategies are urgently needed. Preclinical work shows that augmented passive immunotherapy with P4 peptide increases phagocytic activity and shows promise as a novel therapeutic strategy. Our aim was to determine ex vivo P4 activity in a target population of patients admitted to critical care with severe infection.

Immune Responses in U.S. Military Personnel Who Received Meningococcal Conjugate Vaccine (MenACWY) Concomitantly with Other Vaccines Were Higher than in Personnel Who Received MenACWY Alone.

Immunological responses to vaccination can differ depending on whether the vaccine is given alone or with other vaccines. This study was a retrospective evaluation of the immunogenicity of a tetravalent meningococcal conjugate vaccine for serogroups A, C, W, and Y (MenACWY) administered alone (n = 41) or concomitantly with other vaccines (n = 279) to U.S.

Molecular signatures of antibody responses derived from a systems biology study of five human vaccines.

Many vaccines induce protective immunity via antibodies. Systems biology approaches have been used to determine signatures that can be used to predict vaccine-induced immunity in humans, but whether there is a 'universal signature' that can be used to predict antibody responses to any vaccine is unknown. Here we did systems analyses of immune responses to the polysaccharide and conjugate vaccines against meningococcus in healthy adults, in the broader context of published studies of vaccines against yellow fever virus and influenza virus.

Immunoactivating peptide p4 augments alveolar macrophage phagocytosis in two diverse human populations.

New treatment strategies are urgently needed to overcome early mortality in acute bacterial infections. Previous studies have shown that administration of a novel immunoactivating peptide (P4) alongside passive immunotherapy prevents the onset of septicemia and rescues mice from lethal invasive disease models of pneumococcal pneumonia and sepsis. In this study, using two diverse populations of adult volunteers, we determined whether P4 treatment of human alveolar macrophages would upregulate phagocytic killing of Streptococcus pneumoniae ex vivo.

Interlaboratory standardization of the sandwich enzyme-linked immunosorbent assay designed for MATS, a rapid, reproducible method for estimating the strain coverage of investigational vaccines.

The meningococcal antigen typing system (MATS) sandwich enzyme-linked immunosorbent assay (ELISA) was designed to measure the immunologic cross-reactivity and quantity of antigens in target strains of a pathogen. It was first used to measure the factor H-binding protein (fHbp), neisserial adhesin A (NadA), and neisserial heparin-binding antigen (NHBA) content of serogroup B meningococcal (MenB) isolates relative to a reference strain, or "relative potency" (RP). With the PorA genotype, the RPs were then used to assess strain coverage by 4CMenB, a multicomponent MenB vaccine.

P4-mediated antibody therapy in an acute model of invasive pneumococcal disease.

New treatments against severe bacterial infections are needed because the response to antibiotic treatment is slow in acute settings and is becoming less effective owing to the emergence of antibiotic-resistant pathogens. P4-mediated antibody therapy offers a unique treatment strategy that combines exogenous immunoglobulin with the immunoactivating peptide P4. In an acute model of pneumococcal disease, mice were infected with Streptococcus pneumoniae and treated intravenously or intranasally with P4 and intravenous immunoglobulin (IVIG).

A Novel Innate Immune-Enhancement Strategy Combined with IVIG Rescues Mice from Fatal Staphylococcus aureus Septicemia.

Staphylococcus aureus (SA) is a major community-acquired pathogen. The emergence of drug-resistant strains like, methicillin-resistant SA (MRSA), poses stiff challenges to therapeutic intervention. Passive immune-therapy with specific antibodies is being actively examined to treat fulminant infections with limited success.

Immunotherapy with a combination of intravenous immune globulin and p4 peptide rescues mice from postinfluenza pneumococcal pneumonia.

Alternate therapies are needed for treatment of secondary bacterial pneumonia following influenza. The immunomodulatory peptide P4 has shown promise in mouse models of primary pneumococcal infection. Mice infected with influenza virus and then challenged with Streptococcus pneumoniae were treated with a combination of P4 peptide and intravenous immune globulin.