Subcutaneous immunoglobulin replacement for treatment of humoral immune dysfunction in patients with chronic lymphocytic leukemia.

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) experience hypogammaglobinemia and non-neutropenic infections. In this exploratory proof of concept study, our objective was to determine the prevalence of humoral immunodeficiency in patients with CLL and serum IgG ≥ 400 mg/dL, and to evaluate the efficacy of subcutaneous immunoglobulin (SCIG) in this population. PATIENTS AND METHODS: Patients with CLL with serum IgG ≥ 400 mg/dL were evaluated for serum IgG, IgM, IgA, along with pre/post vaccine IgG titers to diphtheria, tetanus, and Streptococcus pneumoniae. Patients with evidence of humoral dysfunction were treated with SCIG with Hizentra every 7±2 days for 24 weeks. RESULTS: Fifteen patients enrolled with median IgG = 782 mg/dL [IQR: 570 to 827], and 6/15 (40%) responded to vaccination with Td, while 5/15 (33%) responded to vaccination with PPV23. 14/15 (93.3%) demonstrated humoral immunodeficiency as evidenced by suboptimal vaccine responses, and were treated with SCIG. In patients treated with SCIG, serum IgG increased from 670 mg/dL [IQR: 565 to 819] to 1054 mg/dL [IQR: 1040 to 1166] after 24 weeks (95% CI: 271-540). For streptococcus pneumoniae, the median protective serotypes at baseline was 8 [IQR: 4 to 9] and increased to 17 [IQR: 17 to 19] after 24 weeks (95% CI: 6.93-13.72). Non-neutropenic infections (NNI) decreased from 14 to 5 during treatment with SCIG. CONCLUSIONS: Patients with CLL demonstrate humoral immunodeficiency despite IgG > 400 mg/dL. For these patients, SCIG is well tolerated and efficacious in improving serum IgG, specific IgG to streptococcus pneumoniae, and may decrease reliance on antibiotics for the treatment of NNIs. CLINICAL TRIALS REGISTRATION: NCT03730129.

Induction of antibody responses in mice immunized intranasally with Type I interferon as adjuvant and synergistic effect of chitosan.

Type I IFNs are a range of host-derived molecules with adjuvant potential; they have been used for many years in the treatment of cancer and viral hepatitis. Therefore, the safety of IFNs for human use has been established. In this study, we evaluated the mucosal adjuvanticity of IFN-ß administered intranasally to mice with diphtheria toxoid, and suggested a method to improve its adjuvanticity. When IFN-ß alone was used as a mucosal adjuvant, no clear results were obtained. However, simultaneous administration of IFN-ß and chitosan resulted in an enhancement of the specific serum immunoglobulin G (IgG) and IgA antibody responses, the mucosal IgA antibody response, and antitoxin titers. Furthermore, the intranasal administration of IFN-α alone resulted in a greater increase in antibody titer than IFN-ß, and a synergistic effect with chitosan was also observed. These findings suggest that intranasal administration of chitosan and Type I IFNs may display an effective synergistic mucosal adjuvant activity.

Identification of Formaldehyde-Induced Modifications in Diphtheria Toxin.

Diphtheria toxoid is produced by detoxification of diphtheria toxin with formaldehyde. This study was performed to elucidate the chemical nature and location of formaldehyde-induced modifications in diphtheria toxoid. Diphtheria toxin was chemically modified using 4 different reactions with the following reagents: (1) formaldehyde and NaCNBH3, (2) formaldehyde, (3) formaldehyde and NaCNBH3 followed by formaldehyde and glycine, and (4) formaldehyde and glycine. The modifications were studied by SDS-PAGE, primary amino group determination, and liquid chromatography-electrospray mass spectrometry of chymotryptic digests. Reaction 1 resulted in quantitative dimethylation of all lysine residues. Reaction 2 caused intramolecular cross-links, including the NAD+-binding cavity and the receptor-binding site. Moreover, A fragments and B fragments were cross-linked by formaldehyde on part of the diphtheria toxoid molecules. Reaction 3 resulted in formaldehyde-glycine attachments, including in shielded areas of the protein. The detoxification reaction typically used for vaccine preparation (reaction 4) resulted in a combination of intramolecular cross-links and formaldehyde-glycine attachments. Both the NAD+-binding cavity and the receptor-binding site of diphtheria toxin were chemically modified. Although CD4+ T-cell epitopes were affected to some extent, one universal CD4+ T-cell epitope remained almost completely unaltered by the treatment with formaldehyde and glycine.

GM-CSF improves the immune response to the diphtheria-component in a multivalent vaccine.

Multivalent tetanus and diphtheria toxoid containing vaccines belong to the most frequently applied vaccines. However, there is an imbalance in the degree of protection against the two antigens with insufficient long-term protection against diphtheria, particularly in the elderly population. We have previously reported a positive correlation between granulocyte macrophage-colony stimulating factor (GM-CSF) and the production of diphtheria-specific antibodies. Therefore, in the present study we analyzed the effects of in vivo applied recombinant GM-CSF on immunization with multivalent tetanus/diphtheria vaccine in mice of different age. In vivo application of GM-CSF lead to enhanced production of diphtheria-specific antibodies as well as more diphtheria-specific CD4+ T cells following vaccination with multivalent tetanus/diphtheria vaccine. In contrast, the humoral and cellular immune response to the tetanus component was unaltered. Furthermore, application of GM-CSF resulted in more splenic CD11b+ dendritic cells (DCs) with a higher MHC-II expression. GM-CSF also induced a stronger recruitment of CD11b+ DCs to the injected muscle. Most remarkably, GM-CSF was able to boost the diphtheria-specific immune response to the multivalent vaccine in aged mice. This study demonstrates that local administration of GM-CSF is able to improve immune responsiveness to the diphtheria component of multivalent tetanus/diphtheria vaccine in young and old mice. This information could be useful for the future design of vaccines for the elderly.

Augmentation of humoral and cellular immunity in response to Tetanus and Diphtheria toxoids by supercritical carbon dioxide extracts of Hippophae rhamnoides L. leaves.

Hippophae rhamnoides L. commonly known as Seabuckthorn (SBT), a wild shrub of family Elaegnacea, has extensively used for treating various ailments like skin diseases, jaundice, asthma, lung troubles. SBT leaves have been reported to possess several pharmacological properties including immunomodulatory, antioxidant, anti-inflammatory, antimicrobial and tissue regeneration etc. The present study was undertaken to evaluate the adjuvant property of supercritical carbon dioxide extracts (SCEs 300ET and 350ET) of SBT leaves in balb/c mice immunized with Tetanus and Diphtheria toxoids. The dynamic changes in the immune response were measured in terms of humoral and cell-mediated immune responses. We have seen the effect of SCEs on immunoglobulin subtypes and secondary immune response generation. In addition, the effect of SCEs on antigen specific cellular immunity was evaluated. Our results show that SCEs 300ET and 350ET significantly enhanced antibody titers in response to both TT and DT antigens. The secondary immune response generated was significantly increased in case of TT immunized animals. SCEs also enhanced cytokine levels (IFN-γ, IL-4, TNF-α and IL-1ß) and increased lymphoproliferation. Besides, both SCEs did not show any toxic effects. Therefore, the study suggests that SCEs are safe and have potent immunostimulatory activity and hence, seems to be a promising balanced Th1 and Th2 directing immunological adjuvant for various veterinary as well as human vaccines.

Immunogenicity and efficacy of a rationally designed vaccine against vascular endothelial growth factor in mouse solid tumor models.

Vascular endothelial growth factor (VEGF) plays an important role in the progression of various cancers. The VEGF-specific antibody bevacizumab combined with chemotherapy was shown to significantly improve progression-free survival in certain cancers. However, repeated administration is necessary for effective suppression of VEGF, thereby making the therapy expensive and cumbersome. Thus, it is urgent to develop alternative reagents such as VEGF vaccines. Here we report that DTT-VEGF, a VEGF-based antigen consisting of the receptor-binding domain of VEGF and diphtheria toxin T domain (DTT), not only stimulated neutralizing antibody response, but also induced type 1 immune response as well as anti-tumor cytotoxic T lymphocytes in mice when administered with aluminum hydroxide adjuvant. The antibodies triggered by DTT-VEGF immunization inhibited the binding of VEGF to VEGF receptor and downregulated the serum VEGF levels in tumor-bearing mice. VEGF-specific IgG2a and IgG2b antibodies as well as type 1 cytokines were stimulated by DTT-VEGF vaccination. The splenocytes from DTT-VEGF-immunized mice showed cytotoxic activity against B16-F10 cells expressing VEGF. Extensive necrosis with severe hemorrhage and enhanced CD8+ T cell infiltration were observed in tumors from DTT-VEGF-immunized mice. The percentages of CD31+ vascular areas in the tumor sections from DTT-VEGF-immunized mice were significantly lower than those of control mice. DTT-VEGF significantly inhibited tumor growth in preventive and therapeutic vaccination settings in mouse models. Our data suggest that DTT is an effective antigen carrier to break immune self-tolerance and our vaccine design has potential to be used for human cancer therapy.

Vaccine-Derived Immunity in Children With Cancer-Analysis of Anti-Tetanus and Anti-Diphtheria Antibodies Changes after Completion of Antineoplastic Therapy.

BACKGROUND: Cancer survival rates and longevity of patients after therapy have significantly improved during the last decades. Thus durable protection against infections should be provided. The aim of the study was to compare the levels of vaccine-derived antibodies in children with cancer compared to those of healthy children and to investigate how therapy influences the levels of specific antibodies. PROCEDURE: A group of 40 children, diagnosed with acute lymphoblastic leukemia (ALL) or solid tumor (ST), followed in Poznan University of Medical Sciences Department of Pediatric Hematology, Oncology and Bone Marrow Transplantation, were recruited for evaluation of humoral immunity. Antibody levels were checked before treatment and 3, 6, and 12 months after treatment. RESULTS: In patients with ALL or ST, levels of IgG against tetanus and diphtheria were significantly lower than in the control group. Among ALL patients, 9% remained negative for tetanus and diphtheria antibodies 12 months after therapy. Among patients with ST 3 months after chemotherapy, there were no protective antibodies in 12% against tetanus, and in 18% against diphtheria. All patients reconstituted immunity 6 and 12 months after therapy. CONCLUSIONS: Our data show that a considerable number of cancer patients lose immunity against diphtheria and tetanus after therapy. Compared to ST, patients with ALL lose protective antibody levels more often. Patients with ST reconstituted antibodies after the treatment cessation, while levels in ALL patients remained low.

Determining trace amounts and the origin of formaldehyde impurity in Neisseria meningitidis A/C/Y/W-135-DT conjugate vaccine formulated in isotonic aqueous 1× PBS by improved C18-UPLC method.

The ability to accurately measure and report trace amounts of residual formaldehyde impurity in a vaccine product is not only critical in the product release but also a regulatory requirement. In many bacterial or viral vaccine manufacturing procedures, formaldehyde is used either at a live culture inactivation step or at a protein de-toxification step or at both. Reported here is a validated and improved C18-UPLC method (developed based on previously published C-8 HPLC method) to determine the traces of formaldehyde process impurity in a liquid form Neisseria meningitidis A/C/Y/W-135-DT conjugate vaccine formulated in isotonic aqueous 1× PBS. UPLC C-18 column and the conditions described distinctly resolved the 2,4-DNPH-HCHO adduct from the un-reacted 2,4-DNPH as detected by TUV detector at 360 nm. This method was shown to be compatible with PBS formulation and extremely sensitive (with a quantitation limit of 0.05 ppm) and aided to determine formaldehyde contamination sources by evaluating the in-process materials as a track-down analysis. Final nanogram levels of formaldehyde in the formulated single dose vialed vaccine mainly originated from the diphtheria toxoid carrier protein used in the production of the conjugate vaccine, whereas relative contribution from polysaccharide API was minimal.

A palindromic CpG-containing phosphodiester oligodeoxynucleotide as a mucosal adjuvant stimulates plasmacytoid dendritic cell-mediated T(H)1 immunity.

BACKGROUND: CpG oligodeoxynucleotides (ODNs), resembling bacterial DNA, are currently tested in clinical trials as vaccine adjuvants. They have the nuclease-resistant phosphorothioate bond; the immune responses elicited differ according to the CpG ODN sequence and vaccination method. To develop a CpG ODN that can induce plasmacytoid dendritic cell (pDC)-mediated T(H)1 immunity through the mucosa, we constructed phosphodiester G9.1 comprising one palindromic CpG motif with unique polyguanosine-runs that allows degradation similar to naturally occurring bacterial DNA. METHODS: T(H)1 and T(H)2 immunity activation was evaluated by cytokine production pattern and T-bet/GATA-3 ratio in human peripheral blood mononuclear cells and mouse bone marrow cells. Adjuvanticity was evaluated in mice administered G9.1 with diphtheria toxoid (DT) through nasal vaccination. RESULTS: G9.1 exhibited stronger IFN-α-inducing activity than A-class CpG ODN2216 and increased T-bet/GATA-3 ratio by enhancing T-bet expression. Nasally administered G9.1 plus DT induced DT-specific mucosal IgA and serum IgG, but not IgE, responses with antitoxin activity in C57BL/6 and BALB/c mice, possibly due to IFN/BAFF production. Induction of T(H)1, but not T(H)2-type Abs depended completely on pDCs, the first in vivo demonstration by CpG ODNs. CONCLUSIONS: G9.1 is a promising mucosal adjuvant for induction of pDC-mediated T(H)1 immunity.

Generation of a universal CD4 memory T cell recall peptide effective in humans, mice and non-human primates.

CD4T cells play a key role in humoral immunity by providing help to B cells, enabling effective antibody class switching and affinity maturation. Some vaccines may generate a poor response due to a lack of effective MHC class II epitopes, resulting in ineffective helper T cell activation and recall and consequently poor humoral immunity. It may be beneficial to provide a CD4T cell helper peptide with a vaccine particularly in the case of a poorly immunogenic antigen. Such a T cell helper peptide must be promiscuous in its ability to bind a broad range of MHC class II alleles due to broad allelic variation in the human population. We designed a chimeric MHC class II peptide (TpD) with epitopes from tetanus toxoid and diphtheria toxoid, separated by an internal cathepsin cleavage site. TpD was capable of inducing a memory recall response in peripheral blood mononuclear cells from 20/20 human donors. T cells responding to TpD showed a central memory phenotype. Immunization of mice with a synthetic nicotine nanoparticle vaccine containing TpD showed that the peptide was required for robust antibody production and resulted in a long term CD4 memory T cell recall response. As a pre-clinical model two non-human primate species, rhesus macaques and cynomolgus monkeys, were immunized with a nicotine nanoparticle vaccine and evaluated for an anti-nicotine antibody response and TpD specific memory T cells. We found that 4/4 rhesus monkeys had both sustained antibody production and TpD memory T cells for the duration of the experiment (119 days). In addition 30/30 cynomolgus monkeys dosed with nicotine vaccine nanoparticles showed dose-dependent antibody generation and T cell recall response compared to saline injected controls. In summary we have developed a potent universal memory T cell helper peptide (TpD) that is active in vitro in human PBMCs and in vivo in mice and non-human primates.

Selection of a novel anti-nicotine vaccine: influence of antigen design on antibody function in mice.

Anti-nicotine vaccines may aid smoking cessation via the induction of anti-nicotine antibodies (Ab) which reduce nicotine entering the brain, and hence the associated reward. Ab function depends on both the quantity (titer) and the quality (affinity) of the Ab. Anti-nicotine vaccines tested previously in clinical studies had poor efficacy despite high Ab titer, and this may be due to inadequate function if Ab of low affinity were induced. In this study, we designed and synthesized a series of novel nicotine-like haptens which were all linked to diphtheria toxoid (DT) as carrier, but which differed in the site of attachment of linker to nicotine, the nature of linker used, and the handle used to attach the hapten to DT. The resulting hapten conjugates were evaluated in a mouse model, using CpG (a TLR9 agonist) and aluminum hydroxide (Al(OH)3) as adjuvants, whereby Ab titers, affinity and function were evaluated using a radiolabeled nicotine challenge model. A series of additional linkers varying in length, rigidity and polarity were used with a single hapten to generate additional DT-conjugates, which were also tested in mice. Conjugates made with different haptens resulted in various titers of anti-nicotine Ab. Several haptens gave similarly high Ab titers, but among these, Ab affinity and hence function varied considerably. Linker also influenced Ab titer, affinity and function. These results demonstrate that immune responses induced in mice by nicotine-conjugate antigens are greatly influenced by hapten design including site of attachment of linker to nicotine, the nature of linker used, and the handle used to attach the hapten to DT. While both Ab titer and affinity contributed to function, affinity was more sensitive to antigen differences.

Enhancing immunogenicity of a 3'aminomethylnicotine-DT-conjugate anti-nicotine vaccine with CpG adjuvant in mice and non-human primates.

Tobacco smoking is one of the most preventable causes of morbidity and mortality, but current smoking cessation treatments have relatively poor long term efficacy. Anti-nicotine vaccines offer a novel mechanism of action whereby anti-nicotine antibodies (Ab) in circulation prevent nicotine from entering the brain, thus avoiding the reward mechanisms that underpin nicotine addiction. Since antibody responses are typically long lasting, such vaccines could potentially lead to better long-term smoking cessation outcomes. Clinical trials of anti-nicotine vaccines to date have not succeeded, although there was evidence that very high anti-nicotine Ab titers could lead to improved smoking cessation outcomes, suggesting that achieving higher titers in more subjects might result in better efficacy overall. In this study, we evaluated CpG (TLR9 agonist) and aluminum hydroxide (Al(OH)3) adjuvants with a model anti-nicotine antigen comprising trans-3'aminomethylnicotine (3'AmNic) conjugated to diphtheria toxoid (DT). Anti-nicotine Ab titers were significantly higher in both mice and non-human primates (NHP) when 3'AmNic-DT was administered with CpG/Al(OH)3 than with Al(OH)3 alone, and affinity was enhanced in mice. CpG also improved functional responses, as measured by nicotine brain levels in mice after intravenous administration of radiolabeled nicotine (30% versus 3% without CpG), or by nicotine binding capacity of NHP antisera (15-fold higher with CpG). Further improvement should focus on maximizing Ab function, which takes into account both titer and avidity, and this may require improved conjugate design in addition to adjuvants.

Effective humoral immunity against diphtheria and tetanus in patients with systemic lupus erythematosus or myasthenia gravis.

INTRODUCTION: Controversy exists about the effectiveness of vaccine-induced immune response in patients with immunoregulatory disorders. Our aim was to determine the antibody titers to diphtheria and tetanus in patients with either of two autoimmune diseases. METHODS: 279 patients with SLE (205 females, aged 45.0 ± 13.8 years), 158 patients with myasthenia gravis (MG) (101 females, aged 55 ± 18.7 years) and 208 healthy subjects (122 females, aged 48 ± 14.6 years) were enrolled. Serum concentrations of diphtheria-antitoxin-IgG (A-DIPHTH) and tetanus-antitoxoid-IgG (A-TET) were determined with ELISA. RESULTS: Equal proportions of healthy subjects, as well as patients with SLE or MG exhibited proper antibody responses and immune protection against diphtheria and tetanus. In all three test groups, serum concentration of A-DIPHTH decreased significantly (p<0.001) with age throughout the study population, while titers of A-TET dropped only in the elderly (>60-years-old) subjects. There were no significant differences among the groups in the age-related changes of A-TET and A-DIPHTH except that in <40-years-old subjects, A-DIPHTH level was significantly (p=0.029) lower in SLE patients than in controls. CONCLUSIONS: Our findings suggest that the level of vaccine-induced immunity against diphtheria and tetanus infections in patients with SLE or MG is comparable to the healthy population.

Evaluation and characterisation of A and B fragments of Corynebacterium diphtheriae toxin towards recombinant diphtheria vaccine.

BACKGROUND: Diphtheria is a highly communicable disease caused by toxin-producing strains of Corynebacterium diphtheriae. OBJECTIVES: To evaluate the efficacy of A and B subunits of diphtheria toxin (DT-A, DT-B) as potential vaccines against C. diphtheriae. A culture of C. diphtheriae (strain PW 8) was grown on Loeffler plates while Lingood medium was used for production of diphtheria toxin (DT). MATERIALS AND METHODS: DT was purified and digested to obtain pure DT-A and DT-B and detoxified to obtain diphtheria toxin. Four groups of mice were immunised with different antigens (Ag) of C. diphtheriae. RESULTS: The antibody (Ab) titres were significantly increased with immunised groups subsequent to three injections. On the other hand, Ab titres were estimated after the three immunisations and the levels of different Ab isotypes were comparatively measured. The levels of various isotypes immune responses showed variation between immunised groups where the IgG subclasses were significantly increased mainly with DPT immunised group. The IgM and IgA were significantly increased with DT-A more than others. Additionally, the evaluation of the cellular immune responses demonstrated that spleen cells from DPT and DT-A groups gave highly significant proliferative response with production of high levels of IL-2 and IFN-γ (Th1/Th2). Separation and purification of DT gene were performed using polymerase chain reaction (PCR) and sub-cloned in pGEM-T vector, for further studying of recombinant vaccine. CONCLUSION: Our results showed the possibility to prepare a potent recombinant vaccine containing whole DT gene or DT-A against C. diphtheriae or could be used in treatment of cancer as it give high levels of IL-2 and IFN-γ.

Short-term and long-term antibody response by mice after immunization against Neisseria meningitidis B or diphtheria toxoid

Serogroup B Neisseria meningitidis (MenB) is a major cause of invasive disease in early childhood worldwide. The only MenB vaccine available in Brazil was produced in Cuba and has shown unsatisfactory efficacy when used to immunize millions of children in Brazil. In the present study, we compared the specific functional antibody responses evoked by the Cuban MenB vaccine with a standard vaccine against diphtheria (DTP: diphtheria, tetanus, pertussis) after primary immunization and boosting of mice. The peak of bactericidal and opsonic antibody titers to MenB and of neutralizing antibodies to diphtheria toxoid (DT) was reached after triple immunization with the MenB vaccine or DTP vaccine, respectively. However, 4 months after immunization, protective DT antibody levels were present in all DTP-vaccinated mice but in only 20% of the mice immunized against MenB. After 6 months of primary immunization, about 70% of animals still had protective neutralizing DT antibodies, but none had significant bactericidal antibodies to MenB. The booster doses of DTP or MenB vaccines produced a significant antibody recall response, suggesting that both vaccines were able to generate and maintain memory B cells during the period studied (6 months post-triple immunization). Therefore, due to the short duration of serological memory induced by the MenB vaccine (VA-MENGOC-BC® vaccine), its use should be restricted to outbreaks of meningococcal disease.

Cell recruitment and antigen trafficking in afferent lymph after injection of antigen and poly(I:C) containing liposomes, in aqueous or oil-based formulations.

After vaccination, innate cell populations transport antigen from the tissue, via the afferent lymphatic vessels, into the local lymph node where they provide critical signals for the generation of an adaptive immune response. The present study uses a unique lymphatic cannulation model to examine, in real time, changes in afferent lymph after injection of a liposome-based delivery system, incorporating diptheria toxoid (DT) and the innate stimulator, poly(I:C). There was a dramatic but temporal recruitment of innate cell populations over time, with neutrophils and monocytes peaking at 6h and 28h post vaccination respectively. The number of dendritic cells (DC) did not increase over the 198h time period, while lymphocytes were slightly elevated at the latest times, indicating the start of an adaptive response. Monocytes and neutrophils were the predominant cell types transporting antigen at the early time points while DC were the most dominant antigen-carrying cells after 78h, predominantly the Sirp-α(high) DC subtype. Resuspending liposomes in oil instead of aqueous solutions has recently been shown to dramatically increase the level and persistence of an immune response and forms the basis of the novel adjuvant formulations, Vaccimax© and Depovax©. In the present study, formulation of the DT and poly(I:C) containing liposomes in an oil carrier dramatically reduced antigen transport to the draining lymph nodes. Examination of the injection site revealed the creation of an ectopic lymphoid tissue with prominent antigen foci and organized lymphoid cells, providing a possible mechanism for the persistence of an immune response in liposome-in-oil adjuvant formulation. Together, the present studies demonstrate the real-time innate in vivo response to vaccination of two novel liposome-based adjuvant systems and the dramatic effect of different carrier formulations.

Persistence of humoral immunity to tetanus and diphtheria in hematopoietic stem cell transplant recipients after post-transplant immunization.

BACKGROUND: Persistence of humoral immunity was evaluated in 82 hematopoietic stem cell transplant recipients up to 12.5 years after post-transplant immunization against tetanus and diphtheria. PROCEDURE: New immunization, initiated at least 12 months after transplantation, consisted of an average three-dose schedule of vaccine administration on day 1, month 3, and month 12. Serological data were collected at pre-transplant, post-transplant, vaccination, and post-vaccination time points. RESULTS: The first vaccination dose elicited a seroprotective response in most recipients, but the complete vaccine series (usually three-dose schedule) reinforced the specific immunity in most vaccinated cases, that is, 100% and 95.8% seroprotection against tetanus and diphtheria, respectively. Geometric mean concentration post-vaccination tetanus and diphtheria antibody levels persisted at 1.9 IU (95% CI: 1.23-2.94 IU/ml) and 0.20 IU (95% CI: 0.11-0.38 IU/ml) for 7 years, respectively. However, diphtheria antibodies were lost not significantly but much faster and more often than tetanus antibodies, though the seroprotection rates against tetanus and diphtheria remained favorable, that is, 100% (95% CI: 85.2-100%) and 87% (95% CI: 59.5-98.3%), respectively. CONCLUSIONS: Full post-transplant revaccination resulted in long-term persistence of humoral immunity against tetanus and diphtheria in SCT recipients, for an average of 8.6 and 9.0 years, respectively.

Soybean agglutinin coated PLA particles entrapping candidate vaccines induces enhanced primary and sustained secondary antibody response from single point immunization.

Polylactide (PLA) polymer particles entrapping diphtheria toxoid (DT) or tetanus toxoid (TT) were formulated with surface coatings of soybean agglutinin to have dendritic cells (DCs) targeting ability through c-type lectin receptors (CLR). It was observed that soybean agglutinin coating resulted in more association of polymer particles with DCs. Immunization with soybean agglutinin coated polymer particles entrapping DT or TT elicited antibody response better than the plain particles entrapping antigens. Both for TT and DT, single point immunization of soybean agglutinin coated polymer particles along with alum resulted in very high antibody titers; much higher than that observed while immunizing with alum adsorbed antigens or admixture of particle entrapped antigens and alum. More interestingly, single point immunization with soybean agglutinin coated polymer particles also elicited very high secondary antibody response which sustained for more than six weeks in mice. Interactions of different polymeric microparticles formulations with DCs correlated with antibody response. Improved primary and sustained secondary antibody response from single point immunization of antigen entrapped soybean agglutinin coated particles was attributed to the N-linked glycan mediated targeting of polymer particles to DCs.

Revaccination of children after completion of standard chemotherapy for acute lymphoblastic leukaemia: a pilot study comparing different schedules.

Given that a significant proportion of children with acute lymphoblastic leukaemia (ALL) lose immune protection to tetanus, diphtheria, and poliomyelitis, revaccination is indicated after chemotherapy. Our randomized pilot study comparing different revaccination schedules suggests that children with ALL might be revaccinated with non-live vaccines as early as 3 months after chemotherapy.