You are here: Home Research Themes Immune Response

Immune Response

Article Reference Synergistic and feedback signaling mechanisms in the regulation of inflammation in respiratory infections.
Pneumonia, the most typical and frequent lower respiratory tract infection (LRTI), is a leading cause of health problems in the United States. Bacteria represent the most prevailing cause of pneumonia in both children and adults. Although pneumonia with a single bacterial infection is common, a significant portion of patients with pneumonia is polymicrobial. This infection is often complexed with other physiological factors such as cytokines and growth factors. Nontypeable Haemophilus influenzae (NTHi) is the most frequently recovered Gram-negative bacterial pathogen in the respiratory system and induces strong inflammatory responses. NTHi also synergizes with other respiratory pathogens, such as Streptococcus pneumoniae and respiratory viruses and pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α). It is noteworthy that NTHi not only synergizes with growth factors such as transforming growth factor-beta (TGF-β), but also utilizes growth factor receptors such as TGF-β receptor and epidermal growth factor receptor (EGFR), to enhance inflammatory responses. Although appropriate inflammation is a protective response against invading pathogens, an uncontrolled inflammatory response is often detrimental to the host. Thus, inflammation must be tightly regulated. The human immune system has evolved strategies for controlling overactive inflammatory response. One such important mechanism is via regulation of negative feedback regulators for inflammation. CYLD, a multifunctional deubiquitinase, was originally reported as a tumor suppressor, but was recently identified as a negative regulator for nuclear factor-kappa B (NF-κB) signaling. It is induced by NTHi and TNF-α via a NF-κB-dependent mechanism, thereby serving as an inducible negative feedback regulator for tightly controlling inflammation in NTHi infection.
Article Reference PKCθ synergizes with TLR-dependent TRAF6 signaling pathway to upregulate MUC5AC mucin via CARMA1.
CARD-containing MAGUK protein 1 (CARMA1) plays a crucial role in regulating adaptive immune responses upon T-cell receptor (TCR) activation in T cells. Its role in regulating host mucosal innate immune response such as upregulation of mucin remains unknown. Here we show that CARMA1 acts as a key signaling mediator for synergistic upregulation of MUC5AC mucin by bacterium nontypeable Haemophilus influenzae (NTHi) and phorbol ester PMA in respiratory epithelial cells. NTHi-induced TLR-dependent TRAF6-MKK3-p38 MAPK signaling pathway synergizes with PKCθ-MEK-ERK signaling pathway. CARMA1 plays a crucial role in mediating this synergistic effect via TRAF6, thereby resulting in synergistic upregulation of MUC5AC mucin. Thus our study unveils a novel role for CARMA1 in mediating host mucosal innate immune response.
Article Reference Critical role of type 1 plasminogen activator inhibitor (PAI-1) in early host defense against nontypeable Haemophilus influenzae (NTHi) infection.
Respiratory systems are constantly being challenged by pathogens. Lung epithelial cells serve as a first line of defense against microbial pathogens by detecting pathogen-associated molecular patterns (PAMPs) and activating downstream signaling pathways, leading to a plethora of biological responses required for shaping both the innate and adaptive arms of the immune response. Acute-phase proteins (APPs), such as type 1 plasminogen activator inhibitor (PAI-1), play important roles in immune/inflammatory responses. PAI-1, a key regulator for fibrinolysis and coagulation, acts as an APP during acute phase response (APR) such as acute lung injury (ALI), inflammation, and sepsis. However, the role of PAI-1 in the pathogenesis of these diseases still remains unclear, especially in bacterial pneumonia. In this study, we showed that PAI-1 expression is upregulated following nontypeable Haemophilus influenzae (NTHi) infection. PAI-1 knockout (KO) mice failed to generate early immune responses against NTHi. Failure of generating early immune responses in PAI-1 KO mice resulted in reduced bacterial clearance and prolonged disease process, which in turn led to enhanced inflammation at late stage of infection. Moreover, we also found that NTHi induces PAI-1 via activation of TLR2-MyD88-MKK3-p38 MAPK signaling pathway. These data suggest that PAI-1 plays critical role in earl host defense response against NTHi infection. Our study thus reveals a novel role of PAI-1 in infection caused by NTHi, one of the most common gram-negative bacterial pathogens in respiratory systems.
Article Reference Elicitation of epithelial cell-derived immune effectors by outer membrane vesicles of nontypeable Haemophilus influenzae.
Outer membrane vesicles (OMVs) are produced by all Gram-negative microorganisms studied to date. The contributions of OMVs to biological processes are diverse and include mediation of bacterial stress responses, selective packaging and secretion of virulence determinants, modulation of the host immune response, and contributions to biofilm formation and stability. First characterized as transformasomes in Haemophilus, these membranous blebs facilitate transfer of DNA among bacteria. Nontypeable Haemophilus influenzae (NTHI), an opportunistic pathogen of the upper and lower respiratory tracts, produces OMVs in vivo, but there is a paucity of information regarding both the composition and role of OMVs during NTHI colonization and pathogenesis. We demonstrated that purified NTHI vesicles are 20 to 200 nm in diameter and contain DNA, adhesin P5, IgA endopeptidase, serine protease, and heme utilization protein, suggesting a multifaceted role in virulence. NTHI OMVs can bind to human pharyngeal epithelial cells, resulting in a time- and temperature-dependent aggregation on the host cell surface, with subsequent internalization. OMVs colocalize with the endocytosis protein caveolin, indicating that internalization is mediated by caveolae, which are cholesterol-rich lipid raft domains. Upon interaction with epithelial cells, NTHI OMVs stimulate significant release of the immunomodulatory cytokine interleukin-8 (IL-8) as well as the antimicrobial peptide LL-37. Thus, we demonstrated that NTHI OMVs contain virulence-associated proteins that dynamically interact with and invade host epithelial cells. Beyond their ability to mediate DNA transfer in Haemophilus, OMV stimulation of host immunomodulatory cytokine and antimicrobial peptide release supports a dynamic role for vesiculation in NTHI pathogenesis and clinically relevant disease progression.
Article Reference Murine model of chronic respiratory inflammation.
The respiratory mucosa is exposed to the external environment each time we breathe and therefore requires a robust and sophisticated immune defense system. As with other mucosal sites, the respiratory mucosal immune system must balance its response to pathogens while also regulating inflammatory immune cell-mediated tissue damage. In the airways, a failure to tightly control immune responses to a pathogen can result in chronic inflammation and tissue destruction with an overzealous response being deleterious for the host. Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death in the US and both the prevalence of and mortality rate of this disease is increasing annually. COPD is characterized by intermittent disease exacerbation. The causal contribution of bacterial infections to exacerbations of COPD is now widely accepted, accounting for at least 50% of all exacerbations. Non-typeable Haemophilus influenzae and Moraxella catarrhalis (both gram-negative bacteria) along with Streptococcus pneumoniae (a gram-positive bacterium) are the three most common bacterial pathogens that cause respiratory tract infections in COPD patients. The colonization of bacteria in the lower airways is similar to a low-grade smoldering infection that induces chronic airway inflammation. Chronic low-grade infection can induce a persistent inflammatory response in the airways and parenchyma. Inefficient removal of bacteria from the lower respiratory tract is characteristic of chronic bronchitis. Inflammation is believed to be central to the pathogenesis of exacerbations, but a clear understanding of the inflammatory changes during an exacerbation of COPD has yet to emerge. As bacterial colonization of the lung in COPD patients is a chronic inflammatory condition highlighted by frequent bouts of exacerbation and clearance, we sought to reproduce this chronic pathogen-mediated inflammation in a murine model by repeatedly delivering the intact, whole, live bacteria intra-tracheally to the lungs.
Article Reference Anamnestic immune response in 3- to 4-year-old children previously immunized with 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine as 2-dose or 3-dose priming and a booster dose in the first year of life.
Immunogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein d conjugate vaccine (PHiD-CV), administered as 2-dose or 3-dose priming followed by a booster dose, has been described previously. The present study evaluated immunologic memory following PHiD-CV vaccination according to these vaccination schedules.
Article Reference ArcA-regulated glycosyltransferase lic2B promotes complement evasion and pathogenesis of nontypeable Haemophilus influenzae.
Signaling mechanisms used by Haemophilus influenzae to adapt to conditions it encounters during stages of infection and pathogenesis are not well understood. The ArcAB two-component signal transduction system controls gene expression in response to respiratory conditions of growth and contributes to resistance to bactericidal effects of serum and to bloodstream infection by H. influenzae. We show that ArcA of nontypeable H. influenzae (NTHI) activates expression of a glycosyltransferase gene, lic2B. Structural comparison of the lipooligosaccharide (LOS) of a lic2B mutant to that of the wild-type strain NT127 revealed that lic2B is required for addition of a galactose residue to the LOS outer core. The lic2B gene was crucial for optimal survival of NTHI in a mouse model of bacteremia and for evasion of serum complement. The results demonstrate that ArcA, which controls cellular metabolism in response to environmental reduction and oxidation (redox) conditions, also coordinately controls genes that are critical for immune evasion, providing evidence that NTHI integrates redox signals to regulate specific countermeasures against host defense.
Article Reference Effectiveness of engineering the nontypeable Haemophilus influenzae antigen Omp26 as an S-layer fusion in bacterial ghosts as a mucosal vaccine delivery.
The potential of empty bacterial cell envelopes (ghosts) as a delivery system for mucosal immunization was assessed in a rat model and different routes of immunization were evaluated. Animals were mucosally immunized targeting either gut only or gut and lung mucosal sites with Escherichia coli ghosts harbouring the nontypeable Haemophilus influenzae (NTHi) antigen Omp26. Omp26 was expressed as either a part of an S-layer fusion or as a soluble protein in the periplasm. In the gut/lung regime two initial gut targeted inoculations with the ghosts were followed by an intratracheal (IT) boost with purified Omp26. The gut only immunization regime showed a moderate enhancement of bacterial clearance following pulmonary challenge whereas the gut/lung immunization regime resulted in significantly enhanced pulmonary clearance of NTHi. Both immunization regimes induced high levels of Omp26 specific antibodies in the serum of immunized rats, with higher levels in the groups that received the IT boost with purified Omp26. Analysis of IgG isotypes present in serum suggest that the immune response was predominantly of a T-helper1 type. Additionally, immunization induced a significant cellular immune response with lymphocytes from animals vaccinated using the gut/lung regime responding significantly to Omp26 when compared to control groups. The results of this study show that mucosal immunization with recombinant Omp26 in E. coli ghosts followed by a boost with purified Omp26 can induce a specific and protective immune response in a rodent model of acute lung infection.
Article Reference The role of DNA sensing and innate immune receptor TLR9 in otitis media.
Otitis media (OM), a common infectious disease in children, is associated with bacterial middle ear (ME) infection. Toll-like receptors (TLRs) are important mediators of innate immune responses, and TLR9 specifically recognizes the unmethylated cytidine-phosphate-guanosine (CpG) motifs in bacterial DNA. Additional sensors of foreign DNA have recently been identified. The role of DNA sensing and TLR9 was investigated in a murine model of OM induced by non-typeable Haemophilus influenzae (NTHi). Expression of genes related to DNA-sensing pathways involved in innate immunity was assessed via DNA microarray, qPCR and immunohistochemistry. Middle ear responses to NTHi were examined in wild-type and TLR9(-/-) mice by histopathology and bacterial culture. Expression of TLR9 signaling genes was modestly up-regulated during OM, as was TLR9 protein in both ME mucosal cells and infiltrating leukocytes. However, genes known to be regulated by CpG DNA were dramatically up-regulated, as were genes involved in DNA sensing by DIA, Pol-III and AIM2. Toll-like receptor 9 deletion significantly prolonged the inflammatory response induced by NTHi in the ME and delayed bacterial clearance. The results suggest that DNA sensing via TLR9 plays a role in OM pathogenesis and recovery. Alternative forms of DNA sensing may also contribute to OM.
Article Reference Serum intercellular adhesion molecule 1 variations in young children with acute otitis media.
Acute otitis media (AOM) is an inflammatory reaction in the middle ear, most often occurring in young children. Streptococcus pneumoniae, nontypeable Haemophilus influenzae, and Moraxella catarrhalis are the most common bacteria isolated. Intercellular adhesion molecule 1 (ICAM-1) is involved in the innate immune response to infection by microorganisms, in effective antigen presentation, and in subsequent T-cell activation. Here we prospectively studied levels of serum soluble ICAM-1 (sICAM-1) before, at the time of, and after antimicrobial treatment of AOM in a group of 138 children ages 6 to 30 months. Middle ear fluids were collected by tympanocentesis to identify otopathogens. We found that (i) serum levels of sICAM-1 were significantly higher in S. pneumoniae-, nontypeable H. influenzae-, and M. catarrhalis-infected children than in well children (P < 0.001), confirming that a systemic inflammatory response occurs during AOM; (ii) sICAM-1 levels varied from no elevation (110 ng/ml) to elevation to high levels (maximum, 1,470 ng/ml) among children with AOM; (iii) in paired samples, sICAM-1 levels increased 4- to 20-fold when children developed AOM compared to their sICAM-1 levels before infection; and (iv) the level of sICAM-1 returned to the pre-AOM level at the convalescent stage of AOM after successful antimicrobial therapy. We conclude that AOM often causes a systemic inflammatory reaction, as measured by elevation of the serum sICAM-1 level, and that a high variability in sICAM-1 responses occurs with the presence of otopathogens during AOM.
Article Reference The T-helper cell type 1 immune response to gram-negative bacterial infections is impaired in COPD.
The increased susceptibility to bacterial infections in chronic obstructive pulmonary disease (COPD) is critical for exacerbations. Toll-like receptor-4 (TLR4) detects bacteria via LPS and induces IFN-γ-based immune responses. The direct responsiveness of Th1 lymphocytes to LPS is disputed because they lack surface expression of the TLR4 coreceptor CD14.
Article Reference Cigarette smoke inhibits airway epithelial cell innate immune responses to bacteria.
The human upper respiratory tract, including the nasopharynx, is colonized by a diverse array of microorganisms. While the host generally exists in harmony with the commensal microflora, under certain conditions, these organisms may cause local or systemic disease. Respiratory epithelial cells act as local sentinels of the innate immune system, responding to conserved microbial patterns through activation of signal transduction pathways and cytokine production. In addition to colonizing microbes, these cells may also be influenced by environmental agents, including cigarette smoke (CS). Because of the strong relationship among secondhand smoke exposure, bacterial infection, and sinusitis, we hypothesized that components in CS might alter epithelial cell innate immune responses to pathogenic bacteria. We examined the effect of CS condensate (CSC) or extract (CSE) on signal transduction and cytokine production in primary and immortalized epithelial cells of human or murine origin in response to nontypeable Haemophilus influenzae and Staphylococcus aureus. We observed that epithelial production of interleukin-8 (IL-8) and IL-6 in response to bacterial stimulation was significantly inhibited in the presence of CS (P < 0.001 for inhibition by either CSC or CSE). In contrast, epithelial production of beta interferon (IFN-beta) was not inhibited. CSC decreased NF-kappaB activation (P < 0.05) and altered the kinetics of mitogen-activated protein kinase phosphorylation in cells exposed to bacteria. Treatment of CSC with antioxidants abrogated CSC-mediated reduction of epithelial IL-8 responses to bacteria (P > 0.05 compared to cells without CSC treatment). These results identify a novel oxidant-mediated immunosuppressive role for CS in epithelial cells.
Article Reference Microbial interactions in the respiratory tract.
Upper respiratory tract infections are caused by the synergistic and antagonistic interactions between upper respiratory tract viruses and 3 predominant bacterial pathogens: Streptococcus pneumoniae, nontypeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis, which are members of the commensal flora of the nasopharynx. For many bacterial pathogens, colonization of host mucosal surfaces is a first and necessary step in the infectious process. S. pneumoniae and H. influenzae have intricate interactions in the nasopharynx. The host innate immune response may influence these interactions and therefore influence the composition of the colonizing flora and the invading bacteria. S. pneumoniae, nontypeable H. influenzae, and M. catarrhalis can behave as opportunistic pathogens of the middle ear when conditions are optimal. Chronic otitis media (OM) and recurrent OM include a biofilm component. Each of the 3 predominant pathogens of OM can form a biofilm and have been shown to comprise biofilms present on middle ear mucosa specimens recovered from children with recurrent or chronic OM. Some of these characterized biofilms are of mixed bacterial etiology, suggesting that progress made on single-microbe directed strategies for treatment and/or prevention of OM, although highly encouraging, are likely to be inadequate. A significantly greater understanding about microbial physiology is required as it relates to the involvement of biofilms in OM, to identify points in the natural course of the disease that are perhaps more amenable to treatment strategies, as well as to identify biofilm-relevant antigenic targets that would be helpful in the rational design of vaccines to prevent OM.
Article Reference Pneumococcal polysaccharide protein D-conjugate vaccine (Synflorix; PHiD-CV).
The pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV; Synflorix) contains ten capsular polysaccharide serotypes from the bacterium Streptococcus pneumoniae, eight of which are conjugated to a nonlipidated cell-surface liporotein (protein D) of non-typeable Haemophilus influenzae (NTHi) and two of which are conjugated to either tetanus or diphtheria toxoid. In a three-dose primary vaccination schedule in infants aged <6 months, PHiD-CV elicited high immune responses against all pneumococcal serotypes contained in the vaccine and was noninferior to an approved 7-valent pneumococcal conjugate vaccine (7vCRM) for eight of the ten serotypes (five of the seven common to both vaccines). Moreover, functional antibodies were elicited against all vaccine serotypes in an opsonophagocytic activity (OPA) assay. A fourth booster dose of PHiD-CV during the second year of life elicited an anamnestic response against all ten pneumococcal serotypes, as determined by both antibody concentrations and OPA titers. There were no clinically relevant changes in the immunogenicity of PHiD-CV when coadministered with meningococcal serogroup C conjugate or pentavalent whole cell pertussis combination vaccines, and polio vaccines using two different primary vaccination schedules. 11Pn-PD, an 11-valent prototype of PHiD-CV, demonstrated protection against episodes of acute otitis media (AOM) caused by S. pneumoniae and NTHi in infants aged <27 months. The first occurrence of an episode of AOM caused by pneumococcal vaccine serotypes was reduced by 52.6% in 11Pn-PD vaccinees compared with recipients of a control vaccine (primary endpoint). The tolerability profile of PHiD-CV was generally similar to that of 7vCRM.
Article Reference The toll-Like receptor adaptor TRIF contributes to otitis media pathogenesis and recovery.
Toll-like receptor (TLR) signalling is crucial for innate immune responses to infection. The involvement of TLRs in otitis media (OM), the most prevalent childhood disease in developed countries, has been implicated by studies in middle ear cell lines, by association studies of TLR-related gene polymorphisms, and by altered OM in mice bearing mutations in TLR genes. Activated TLRs signal via two alternative intracellular signaling molecules with differing effects; MyD88 (Myeloid differentiation primary response gene 88) inducing primarily interleukin expression and TRIF (Tir-domain-containing adaptor inducing interferon beta) mediating type I interferon (IFN) expression. We tested the hypothesis that TRIF and type I IFN signaling play a role in OM, using a murine model of OM induced by non-typeable Haemophilus influenzae (NTHi). The ME inflammatory response to NTHi was examined in wild-type (WT) and TRIF-/- mice by qPCR, gene microarray, histopathology and bacterial culture.
Article Reference Breast-feeding is associated with a reduced frequency of acute otitis media and high serum antibody levels against NTHi and outer membrane protein vaccine antigen candidate P6.
Nontypeable Haemophilus influenzae (NTHi) causes acute otitis media (AOM) in infants. Breast-feeding protects against AOM and/or nasopharyngeal (NP) colonization; however, the mechanism of protection is incompletely understood. Children with AOM and healthy children were studied according to feeding status: breastfed,breast/formula fed, or formula fed. Cumulative episodes of AOM, ELISA titers of serum IgG antibodies to whole-cell NTHi and vaccine candidate outer membrane protein P6, bactericidal titers of serum and NP colonization by NTHi were assessed. A lower incidence of AOM was found in breast- versus formula-fed children. Levels of specific serum IgG antibody to NTHi and P6 were highest in breast-fed, intermediate in breast/formula fed, and lowest in formula-fed infants. Serum IgG antibody to P6 correlated with bactericidal activity against NTHi. Among children with AOM, the prevalence of NTHi in the NP was lower in breast- versus nonbreast-fed infants. We conclude that breast-feeding shows an association with higher levels of antibodies to NTHi and P6, suggesting that breast-feeding modulates the serum immune response to NTHi and P6. Higher serum IgG might facilitate protection against AOM and NP colonization in breast-fed children.
Article Reference The relationship between undernutrition and humoral immune status in children with pneumonia in Papua New Guinea.
Malnutrition is a significant risk factor for childhood infectious diseases in developing countries, including Papua New Guinea (PNG). Whilst the mechanisms are not fully understood there is little doubt that impairment of immune function is a major contributing factor in enhancing disease susceptibility in malnourished children. This susceptibility has been clearly shown for pneumonia in PNG. The aim of this study was to examine the effect of undernutrition on the humoral immune profile in children less than 60 months of age with pneumonia. The study was cross-sectional with measurements of nutritional status and parameters of the immune response being assessed simultaneously. The children were grouped according to age for the purpose of comparative analysis. The children were from the Goroka region of the Eastern Highlands Province of PNG and had been admitted to hospital with moderate-severe pneumonia. They were classified as undernourished (less than 80% weight for age) or nourished (greater than or equal to 80% weight for age). Serum albumin, IgG, IgA and IgM and salivary albumin and IgA were measured. Antibodies to nontypeable Haemophilus influenzae outer membrane protein and Escherichia coli O antigen were also determined in serum and saliva. Undernourished children aged less than 49 months had lower levels of serum albumin than nourished children throughout this age range. Lower values of salivary IgA were observed in infants (less than 13 months of age) than in older children, with a larger proportion of younger children having no detectable IgA. The age-related immunological profile was similar in undernourished and nourished children. At different age intervals the concentration of immunoglobulins in serum and saliva from undernourished children was generally found to be less than or the same as that from nourished children. In most cases undernourished children had lower levels of specific antibodies than nourished children but for some antibodies in some age groups the levels in the undernourished were higher. In conclusion, undernutrition was associated with hypoalbuminaemia and reduced humoral immune responses in children with pneumonia but its immunological effects varied with age in an unpredictable way.
Article Reference Serial isolates of persistent Haemophilus influenzae in patients with chronic obstructive pulmonary disease express diminishing quantities of the HMW1 and HMW2 adhesins.
In patients with chronic obstructive pulmonary disease (COPD), the lower respiratory tract is commonly colonized by bacterial pathogens, including nontypeable Haemophilus influenzae. The H. influenzae HMW1 and HMW2 adhesins are homologous proteins that promote bacterial adherence to respiratory epithelium and are the predominant targets of the host immune response. These adhesins undergo graded phase variation, controlled by the numbers of 7-bp repeats upstream of the HMW1 and HMW2 structural genes (hmw1A and hmw2A, respectively). In this study, we examined the levels of HMW1 and HMW2 expressed by H. influenzae isolates collected serially from patients with COPD. We found that expression of HMW1 and HMW2 in a given strain decreased over time in a majority of patients, reflecting progressive increases in the numbers of 7-bp repeats and associated with high serum titers of HMW1/HMW2-specific antibodies. We speculate that the presence of high titers of antibodies against the HMW1 and HMW2 adhesins and other immune factors in the lower respiratory tracts of patients with COPD may result in gradual selection for bacteria with reduced levels of HMW1 and HMW2.
Article Reference Safety of the 11-valent pneumococcal vaccine conjugated to non-typeable Haemophilus influenzae-derived protein D in the first 2 years of life and immunogenicity of the co-administered hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio virus, Haemophilus influenzae type b and control hepatitis A vaccines.
This randomized (1:1), double-blind, multicenter study, included 4,968 healthy infants to receive either the 11-valent pneumococcal protein D (PD)-conjugate study vaccine or the hepatitis A vaccine (HAV) (control) at 3, 4, 5, and 12-15 months of age. The three-dose primary course of both vaccines was co-administered with combined hexavalent DTPa-HBV-IPV/Hib vaccine. The pneumococcal PD-conjugate study vaccine did not impact the immune response of co-administered hexavalent vaccine and the control HAV vaccine induced seropositivity (antibodies >or=15 mIU/mL) in all infants. The incidence of solicited symptoms was higher with the 11-valent pneumococcal PD-conjugate study vaccine, yet similar to that induced by concomitant DTPa-HBV-IPV/Hib vaccine. Overall, the reactogenicity and safety profile of the 11-valent pneumococcal PD-conjugate vaccine when co-administered with the hexavalent DTPa-HBV-IPV/Hib vaccine, as well as the immunogenicity of the co-administered hexavalent vaccine, were consistent with previous reports for the licensed DTPa-HBV-IPV/Hib and pneumococcal conjugate vaccines.
Article Reference Promiscuous peptides on the nontypeable Haemophilus influenzae P6 outer membrane protein.
P6 outer membrane protein is one of the candidates for a vaccine formulation against nontypeable Haemophilus influenzae (NTHi) infection. As otitis-prone children who have recurrent episodes of acute otitis media because of NTHi show an impaired immune response to P6, an innovative approach to vaccination is required to augment their immune response.