Search

Background: Rituximab is an anti-CD20 chimeric antibody used to treat autoimmune conditions and B cell neoplasms. We characterized immunoglobulin (Ig) levels and vaccine responses in rituximab-treated B cell non-Hodgkin lymphoma (NHL) patients. Patients with impaired vaccine responses were offered therapy with 20% subcutaneous (subq) Ig., Patients and Methods: Patients with a biopsy-proven diagnosis of B cell NHL who had received rituximab within the past 24 months were eligible for the study and underwent the following immune evaluation: serum IgG, IgM, IgA, IgE, T/B cell lymphocyte panel, and pre/post vaccine IgG titers to diphtheria, tetanus, and streptococcus pneumoniae. Patients were vaccinated with tetanus, diphtheria and pneumococcal polysaccharide vaccine. Patients with abnormal vaccine responses were offered prophylactic subq Ig for 52 weeks., Results: Fifteen patients with NHL were enrolled in the study. The median IgG was 628 mg/dL [interquartile range, 489-718 mg/dL]. Three (20%) of 15 patients responded to diphtheria vaccination, 1 (6.7%) of 15 responded to tetanus vaccination, and 3 (20%) of 15 responded to vaccination to streptococcus pneumoniae. Thirteen (86.7%) of 15 met criteria for humoral immunodeficiency. Ten patients received subq Ig, and experienced a significant increase in serum IgG (P = .008). There were no serious adverse events, and there was a decrease in nonneutropenic infections while on subq Ig therapy., Conclusions: Patients with NHL treated with rituximab may have significant humoral immunodeficiency as defined by abnormal vaccine responses even in the setting of relatively normal IgG levels. For these patients, subq Ig replacement therapy is well-tolerated and efficacious in improving serum IgG, and may decrease reliance on antibiotics for the treatment of nonneutropenic infections., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Asthma is an allergic airway disease (AAD) characterized by eosinophilic inflammation, mucus hypersecretion, and airway hyper responsiveness, and it is caused by dysregulated immune responses. Conversely, regulatory T cells (Tregs) control aberrant immune responses and maintain homeostasis. Recent evidence suggests that Streptococcus pneumoniae, including its components as well as a live attenuated mutant, and pneumococcal infection induce Tregs and can thus potentially be harnessed therapeutically for asthma treatment. Previously, a pep27 deletion mutant (Δpep27) demonstrated a significantly attenuated virulence in a sepsis model, and Δpep27 immunization induced serotype-nonspecific protection against S. pneumoniae infection, as well as influenza virus, possibly via an immune tolerance mechanism. Here, the potential of Δpep27 immunization for asthma protection was studied. Mice were immunized intranasally with Δpep27 before or after ovalbumin sensitization and subsequent challenge. Δpep27 immunization suppressed hallmark features of AAD, including antigen-specific type 2 helper T cell cytokine and antibody responses, peripheral and pulmonary eosinophil accumulation, and goblet cell hyperplasia. Thus, a Δpep27 vaccine may be highly feasible as a preventive or therapeutic agent for asthma., (Copyright © 2019. Published by Elsevier Inc.)

Developing effective mucosal subunit vaccine for the Streptococcus pneumoniae has been unsuccessful mainly because of their poor immunogenicity with insufficient memory T and B cell responses. We thus address whether such limitation can be overcome by introducing effective adjuvants that can enhance immunity and show here that polysorbitol transporter (PST) serves as a mucosal adjuvant for a subunit vaccine against the Streptococcus pneumoniae. Pneumococcal surface protein A (PspA) with PST adjuvant induced protective immunity against S. pneumoniae challenge, especially long-term T and B cell immune responses. Moreover, we found that the PST preferentially induced T helper (Th) responses toward Th2 or T follicular helper (Tfh) cells and, importantly, that the responses were mediated through antigen-presenting cells via activating a peroxisome proliferator-activated receptor gamma (PPAR-γ) pathway. Thus, these data indicate that PST can be used as an effective and safe mucosal vaccine adjuvant against S. pneumoniae infection. STATE OF SIGNIFICANCE: In this study, we suggested the nanoparticle forming adjuvant, PST works as an effective adjuvant for the pneumococcal vaccine, PspA. The PspA subunit vaccine together with PST adjuvant efficiently induced protective immunity, even in the long-term memory responses, against Streptococcus pneumoniae lethal challenge. We found that PspA with PST adjuvant induced dendritic cell activation followed by follicular helper T cell responses through PPAR-γ pathway resulting long-term memory antibody-producing cells. Consequently, in this paper, we suggest the mechanism for safe nanoparticle forming subunit vaccine adjuvant against pneumococcal infection., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Streptococcus pneumoniae is a major human pathogen responsible for the majority of bacterial pneumonia cases as well as invasive pneumococcal diseases with high mortality and morbidity. Use of conjugate vaccines targeting the pneumococcal capsule has dramatically reduced the incidence of invasive diseases, and there are active efforts to further improve the conjugate vaccines. However, in children new pneumococcal vaccines can no longer be tested with placebo-based clinical trials because effective vaccines are currently available. Thus, vaccine studies must depend on surrogate markers of vaccine efficacy. Although traditional antibody levels (e.g., ELISA) are useful as a surrogate marker of protection, they have limitations, and a bioassay measuring the capacity of antibodies to opsonize pneumococci has been developed. This opsonophagocytosis assay (OPA) replicates the in vivo mechanism of antibody protection and should therefore better reflect protection by vaccine-induced antibodies. Technical improvements of OPA have made this bioassay rapid, multiplexed, and practical for analyzing small samples including those from children. Strong correlations between ELISA and OPA have been observed in many studies of young children. However, poor correlations have been found in some important clinical situations (such as determination of protection by cross-reactive antibodies) and populations (such as elderly adults and immunodeficient patients). In these settings, OPA has become a useful supplementary measure of pneumococcal vaccine immunogenicity. Current efforts to standardize OPA will further expand its uses.

Although effective in the treatment of immunodysregulatory diseases such as psoriasis, targeted immunosuppressive agents may confer risks of both enhanced susceptibility to infection and decreased responsiveness to vaccination. In a recent study, Krueger et al. (this issue) investigated these issues by testing the immune response to both a model antigen and a therapeutic vaccination in psoriasis patients during and after treatment with an LFA-1 inhibitor, efalizumab.

Efalizumab is a humanized monoclonal CD11a antibody approved for treatment of psoriasis. Its immunomodulatory effects led us study how immune responses are modified and the possible consequences for vaccinations in clinical practice. This was a randomized, single-blind, placebo-controlled, parallel-group study of 12 weeks of subcutaneous efalizumab treatment of patients with moderate psoriasis. Bacteriophage phiX174 was used as a model neoantigen to assess T-cell-dependent humoral immunity. Tetanus booster vaccine, pneumococcal vaccine, and intracutaneous skin tests were administered to further evaluate humoral and cellular immune responses. During efalizumab treatment, both primary and secondary antibody responses to phiX174, including IgM/IgG isotype switch, were reduced. There appeared to be naïve T-cell anergy to a neoantigen (phiX174) during active CD11a blockade, without tolerance to the antigen after efalizumab withdrawal. Secondary humoral immune responses to tetanus booster during treatment were reduced, but antibody titer increases led to protective levels. Responses to pneumococcal vaccination 6 weeks after withdrawal from efalizumab were not affected. Cellular immune responses to intracutaneous recall antigens were reduced during treatment and returned to pretreatment conditions after withdrawal. These results expand our knowledge of how immune responses are modulated in humans by CD11a blockade and have implications for vaccinations of patients treated with this agent.

Background: When seven-valent pneumococcal conjugate vaccine was introduced in the USA, many children were vaccinated on schedules that differed from those tested in clinical trials. Our aim was to assess the effectiveness of the vaccine against various pneumococcal serotypes, and to measure the effectiveness of the recommended dose schedule and of catch-up and incomplete schedules., Methods: Invasive disease, defined as isolation of pneumococcus from a sterile site, was identified in children aged 3-59 months through the US Centers for Disease Control and Prevention's Active Bacterial Core surveillance. We tested isolates for serotype and antimicrobial susceptibility. Three controls, matched for age and zip code were selected for each case. We calculated the matched odds ratio for vaccination using conditional logistic regression, controlling for underlying conditions. Vaccine effectiveness was calculated as one minus the adjusted matched odds ratio times 100%., Findings: We enrolled 782 cases and 2512 controls. Effectiveness of one or more doses against vaccine serotypes was 96% (95% CI 93-98) in healthy children and 81% (57-92) in those with coexisting disorders. It was 76% (63-85) against infections that were not susceptible to penicillin. Vaccination prevented disease caused by all seven vaccine serotypes, and by vaccine-related serotype 6A. Several schedules were more protective than no vaccination; three infant doses with a booster were more protective against vaccine-type disease than were three infant doses alone (p=0.0323)., Interpretation: The seven-valent pneumococcal conjugate vaccine prevents invasive disease in both healthy and chronically ill children. The vaccine is effective when used with various non-standard schedules.