Impaired Antibody Responses Research Articles

Impaired antibody response and phagocytosis in goats fed a diet low in cobalt

Cobalt (Co) is utilized by rumen microflora to produce vitamin B12. The aim of the present study was to determine whether feeding newly-weaned goats a diet containing low levels of Co results in impairment of neutrophil function, antibody production and/or lymphocyte proliferative responses. Forty, ten week old goats were fed a commercially-prepared concentrate (150g/day) and Rhodesgrass hay ad libitum. This diet contained Co at <0.1mg/kg dry matter. The goats were divided into a control group and a treated group (both n=20). Goats in the treated group were supplemented with bi-monthly subcutaneous injections of 2mg of hydroxycobalamin. Two months after weaning, the goats were immunized with keyhole limpet haemocyanin (KLH). A luminol-dependent chemiluminescence (CL) assay was employed to measure the oxidative respiratory burst of neutrophils during phagocytosis of zymosan A. The lymphocyte proliferative response to phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) was assessed. The controls goats demonstrated a significantly lower antibody (IgG) response to KLH compared with the Co-supplemented goats that was apparent 1 week post immunization and was maintained for the 8 week observation period. Neutrophils from the Co-restricted group demonstrated significantly lower CL responses to opsonized zymosan A. Lymphocytes from the control and treated goats did not differ in their mitogenic responses to PHA and PWM. These results demonstrate that goats fed a diet low in Co exhibited impaired antibody and phagocytic responses.

Common Variable Immunodeficiency.

Common variable immunodeficiency (CVID) is the most common primary immunodeficiency of young adolescents and adults which also affects the children. The disease remains largely under-diagnosed in India and Southeast Asian countries. Although in majority of cases it is sporadic, disease may be inherited in a autosomal recessive pattern and rarely, in autosomal dominant pattern. Patients, in addition to frequent sino-pulmonary infections, are also susceptible to various autoimmune diseases and malignancy, predominantly lymphoma and leukemia. Other characteristic lesions include lymphocytic and granulomatous interstitial lung disease, and nodular lymphoid hyperplasia of gut. Diagnosis requires reduced levels of at least two immunoglobulin isotypes: IgG with IgA and/or IgM and impaired specific antibody response to vaccines. A number of gene mutations have been described in CVID; however, these genetic alterations account for less than 20% of cases of CVID. Flow cytometry aptly demonstrates a disturbed B cell homeostasis with reduced or absent memory B cells and increased CD21(low) B cells and transitional B cell populations. Approximately one-third of patients with CVID also display T cell functional defects. Immunoglobulin therapy remains the mainstay of treatment. Immunologists and other clinicians in India and other South East Asian countries need to be aware of CVID so that early diagnosis can be made, as currently, majority of these patients still go undiagnosed.

Inactivation of nuclear GSK3β by Ser(389) phosphorylation promotes lymphocyte fitness during DNA double-strand break response.

Variable, diversity and joining (V(D)J) recombination and immunoglobulin class switch recombination (CSR) are key processes in adaptive immune responses that naturally generate DNA double-strand breaks (DSBs) and trigger a DNA repair response. It is unclear whether this response is associated with distinct survival signals that protect T and B cells. Glycogen synthase kinase 3β (GSK3β) is a constitutively active kinase known to promote cell death. Here we show that phosphorylation of GSK3β on Ser389 by p38 MAPK (mitogen-activated protein kinase) is induced selectively by DSBs through ATM (ataxia telangiectasia mutated) as a unique mechanism to attenuate the activity of nuclear GSK3β and promote survival of cells undergoing DSBs. Inability to inactivate GSK3β through Ser389 phosphorylation in Ser389Ala knockin mice causes a decrease in the fitness of cells undergoing V(D)J recombination and CSR. Preselection-Tcrβ repertoire is impaired and antigen-specific IgG antibody responses following immunization are blunted in Ser389GSK3β knockin mice. Thus, GSK3β emerges as an important modulator of the adaptive immune response.

N-WASP is required for B-cell–mediated autoimmunity in Wiskott-Aldrich syndrome

AbstractMutations of the Wiskott-Aldrich syndrome gene (WAS) are responsible for Wiskott-Aldrich syndrome (WAS), a disease characterized by thrombocytopenia, eczema, immunodeficiency, and autoimmunity. Mice with conditional deficiency of Was in B lymphocytes (B/WcKO) have revealed a critical role for WAS protein (WASP) expression in B lymphocytes in the maintenance of immune homeostasis. Neural WASP (N-WASP) is a broadly expressed homolog of WASP, and regulates B-cell signaling by modulating B-cell receptor (BCR) clustering and internalization. We have generated a double conditional mouse lacking both WASP and N-WASP selectively in B lymphocytes (B/DcKO). Compared with B/WcKO mice, B/DcKO mice showed defective B-lymphocyte proliferation and impaired antibody responses to T-cell-dependent antigens, associated with decreased autoantibody production and lack of autoimmune kidney disease. These results demonstrate that N-WASP expression in B lymphocytes is required for the development of autoimmunity of WAS and may represent a novel therapeutic target in WAS.

Common variable immunodeficiency associated with microdeletion of chromosome 1q42.1-q42.3 and inositol 1,4,5-trisphosphate kinase B (ITPKB) deficiency.

Common variable immunodeficiency (CVID) is a heterogenous disorder characterized by hypogammaglobulinemia and impaired specific antibody response and increased susceptibility to infections, autoimmunity and malignancies. A number of gene mutations, including ICOS, TACI and BAFF-R, and CD19, CD20, CD21, CD81, MSH5 and LRBA have been described; however, they account for approximately 20–25% of total cases of CVID. In this study, we report a patient with CVID with an intrinsic microdeletion of chromosome 1q42.1-42.3, where gene for inositol 1,3,4, trisphosphate kinase β (ITPKB) is localized. ITPKB has an important role in the development, survival and function of B cells. In this subject, the expression of ITPKB mRNA as well as ITKPB protein was significantly reduced. The sequencing of ITPKB gene revealed three variants, two of them were missense variants and third was a synonymous variant; the significance of each of them in relation to CVID is discussed. This case suggests that a deficiency of ITPKB may have a role in CVID.

A plasma cell differentiation quality control ablates B cell clones with biallelic Ig rearrangements and truncated Ig production

Aberrantly rearranged immunoglobulin (Ig) alleles are frequent. They are usually considered sterile and innocuous as a result of nonsense-mediated mRNA decay. However, alternative splicing can yield internally deleted proteins from such nonproductively V(D)J-rearranged loci. We show that nonsense codons from variable (V) Igκ exons promote exon-skipping and synthesis of V domain-less κ light chains (ΔV-κLCs). Unexpectedly, such ΔV-κLCs inhibit plasma cell (PC) differentiation. Accordingly, in wild-type mice, rearrangements encoding ΔV-κLCs are rare in PCs, but frequent in B cells. Likewise, enforcing expression of ΔV-κLCs impaired PC differentiation and antibody responses without disturbing germinal center reactions. In addition, PCs expressing ΔV-κLCs synthesize low levels of Ig and are mostly found among short-lived plasmablasts. ΔV-κLCs have intrinsic toxic effects in PCs unrelated to Ig assembly, but mediated by ER stress-associated apoptosis, making PCs producing ΔV-κLCs highly sensitive to proteasome inhibitors. Altogether, these findings demonstrate a quality control checkpoint blunting terminal PC differentiation by eliminating those cells expressing nonfunctionally rearranged Igκ alleles. This truncated Ig exclusion (TIE) checkpoint ablates PC clones with ΔV-κLCs production and exacerbated ER stress response. The TIE checkpoint thus mediates selection of long-lived PCs with limited ER stress supporting high Ig secretion, but with a cost in terms of antigen-independent narrowing of the repertoire.

Effect of complement Factor H on anti-FHbp serum bactericidal antibody responses of infant rhesus macaques boosted with a licensed meningococcal serogroup B vaccine

FHbp is a major serogroup B meningococcal vaccine antigen. Binding of complement Factor H (FH) to FHbp is specific for human and some non-human primate FH. In previous studies, FH binding to FHbp vaccines impaired protective anti-FHbp antibody responses. In this study we investigated anti-FHbp antibody responses to a third dose of a licensed serogroup B vaccine (MenB-4C) in infant macaques vaccinated in a previous study with MenB-4C. Six macaques with high binding of FH to FHbp (FHhigh), and six with FHlow baseline phenotypes, were immunized three months after dose 2. After dose 2, macaques with the FHlow baseline phenotype had serum anti-FHbp antibodies that enhanced FH binding to FHbp (functionally converting them to a FHhigh phenotype). In this group, activation of the classical complement pathway (C4b deposition) by serum anti-FHbp antibody, and anti-FHbp serum bactericidal titers were lower after dose 3 than after dose 2 (p<0.02). In macaques with the FHhigh baseline phenotype, the respective anti-FHbp C4b deposition and bactericidal titers were similar after doses 2 and 3. Two macaques developed serum anti-FH autoantibodies after dose 2, which were not detected after dose 3. In conclusion, in macaques with the FHlow baseline phenotype whose post-dose 2 serum anti-FHbp antibodies had converted them to FHhigh, the anti-FHbp antibody repertoire to dose 3 was skewed to less protective epitopes than after dose 2. Mutant FHbp vaccines that eliminate FH binding may avoid eliciting anti-FHbp antibodies that enhance FH binding, and confer greater protection with less risk of inducing anti-FH autoantibodies than FHbp vaccines that bind FH.

Extending the Debate on Poor Response to Hepatitis B Virus Vaccination in Children With Celiac Disease: Which Question Remains?

Dear Editor, A poorer response to hepatitis B vaccination, in coeliac subjects, compared to healthy subjects, has been largely debated. Almost all authors postulated that human leukocyte antigen (HLA) genotype DQ2, found in 90 - 95% of coeliac patients, could represent the main cause in determining the impaired antibody response to recombinant HBV vaccine (1), as well as observed also in healthy not responder subjects. However it has been supposed that gluten intake could represent the main factor in influencing a poorer response to vaccine, since in several studies, it has been observed that the percentage of responders in patients compliant with a gluten free diet (GFD) was similar to healthy subjects (2, 3). Since type I diabetes (T1DM) and coeliac disease (CD) have the same genetic background, given by the HLA molecules that have also been identified as haplotypes associated with unresponsiveness to hepatitis B virus (HBV) vaccination (DR3 and DR4 for T1DM, DQ2 and DQ8 for CD), we firstly compared three different groups of patients, corresponding to T1DM, CD and DMT1-CD, that had in common the same HLA haplotypes, to establish the weight of specific haplotypes of HLA and/or gluten that could favor a poorer response to HBV vaccine. In 30 children suffering from both CD and DMT1, vaccinated by the administration of three doses of vaccine (Engerix-B, Glaxo Smith Kline, London, United Kingdome) at the age of 3, 5 and 11 months of life, according to the national vaccination schedule, we discovered 16 (53.3%) non-responders. This percentage was similar to a previous study on 60 coeliac patients (4), although not significantly higher, compared to a previous study on 100 diabetics (5) (Table 1). Table 1. Characteristics of Patients With Type 1 Diabetes Mellitus, Celiac Disease and Associated Type 1 Diabetes Mellitus/Coeliac Disease a As the mean age and the anti-HBs antibodies titers was similar between coeliacs and coeliacs/diabetics, we consider that the presence of T1DM and its HLA haplotype seems to not decrease anti-HBs antibodies production and percentage of responders. The open question is: what is the role of gluten in this matter? Comparing the T1DM/CD and T1DM, in which both groups had a similar HLA haplotype, we found a higher non-significant percentage of non-responders in T1DM/CD than in T1DM (53.3% vs. 38.2%), although the first group even had a significantly lower mean age (P < 0.0001), which usually is associated to a higher titer of anti HBs antibodies (P < 0.02) and a higher percentage of responders, as we also found in our study (Table 1). The question still remains open: what is the role of gluten in this matter? First of all, we observed that the percentage of non-responders is higher in T1DM/CD patients, compared with diabetics (53.3% vs. 38.2%). However, if we compare the first group with coeliacs, the percentage of non-responders is similar (53.3% vs. 50%). As the genetic substrate of HLA haplotypes, in the two diseases, is the same, this comparison indirectly confirms that gluten certainly represents a second variable, which favors a further decrease of efficacy to HBV vaccine, beyond the HLA system. As written in 1890 by in the chapter “The Science of Deduction” of the book “The Sign of Four, eliminate all other factors and the one which remains must be the truth (6).”

CVID-Induced Diarrhea: A Rare Cause of Chronic Diarrhea

Introduction: Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by impaired B-cell differentiation with defective immunoglobulin production. We report a case of chronic non-infectious diarrhea associated with CVID. Case: A 59 years-old female with history of rheumatoid arthritis, recurrent sinus infections, recurrent urinary tract infections, and hypothyroidism was referred to gastroenterology clinic for chronic diarrhea and fecal incontinence for several months. She had several bowel movements a day which she described as soft to loose with occasional abdominal pain. No systemic symptoms of fever, chills, hematochezia, melena, or weight loss. Her physical examination including vital signs was unremarkable. Her CBC, BMP, celiac panel, TSH, and stool studies were unremarkable. Her EGD and colonoscopy was unremarkable. She was empirically treated with rifaximin for bacterial overgrowth with recurrence of her symptoms after stopping the antibiotics. She was started on loperamide and dicyclomine on as needed basis with improvement in her symptoms. For her fecal incontinence, anorectal manometry with balloon defecography revealing low sphincter pressures, intact neurological reflexes, and prolonged balloon expulsion time. She also underwent rectal ultrasound which showed possible defect at the internal and external anal sphincters. She was managed conservatively. Due to her history of recurrent sinus infection, urinary tract infections, she was referred to immunology for evaluation of immune deficiency. She was diagnosed with CVID. She was started on treatment for CVID. Soon after treatment initiation, her diarrhea resolved. Discussion: CVID is a primary immune deficiency characterized by low levels of antibodies (IgG, IgA, IgM), normal or decreased B-cell numbers, or impaired antibody response to infections. Gastrointestinal manifestations, including malabsorption, diarrhea, and weight loss, are the most common presentation. Mild watery diarrhea can be seen in up to 20% of patients with CVID and 10% have been reported to have severe enteropathy. Treatment of CVID by steroids or other immunosuppressive agents generally improves the GI symptoms. Therefore, immunodeficiency should be kept in mind in patient with chronic non-infectious diarrhea, even in the absence of recurrent infections.

Immunosuppressive drugs impairs antibody response of the polysaccharide and conjugated pneumococcal vaccines in patients with Crohn's disease

BackgroundPatients with Crohn's disease (CD) have a higher risk of infectious diseases including pneumococcal infections, and the risk increases with immunotherapy. The primary endpoint of this study was to investigate the specific antibody response to two pneumococcal vaccines in CD patients with and without immunosuppressive treatment four weeks post vaccination. MethodsIn a randomized trial of the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal conjugated vaccine (PCV13), a group of CD patients treated with immunosuppressive drugs (IS) alone or in combination with TNF-α antagonists were compared to a group of CD patients not treated with any of these drugs (untreated). Specific pneumococcal antibody concentrations were measured against 12 serotypes common to the two vaccines before and 4 week after vaccination. ResultsPCV13 induced a significantly higher antibody response for one serotype (23F) in IS treated patients and for two serotypes (9V and 23F) in untreated patients compared to CD patients vaccinated with PPV23. Untreated PPV23 recipients had higher responses for serotypes 9V and 18C compared to IS+TNF-α treated PPV23 recipients. Comparison between treatment groups showed that immunosuppressive treatment impaired the antibody response to both vaccines and that TNF-a treatment further conveyed additional impairment of the response. ConclusionPCV13 induces higher antibody response for some serotypes compared to PPV23. In addition, CD patients treated with immunosuppressive drugs alone or in combination with TNF-α antagonists had an impaired antibody response to both PPV23 and PCV13 compared to patients not receiving any of these treatments.The study has been registered in the European Clinical Trials Database (EudraCT, record no 2012-002867-86) and ClinicalTrials.gov (record no. NCT01947010).

TNF and regulatory T cells are critical for sepsis-induced suppression of T cells.

The immune system in sepsis is impaired as seen by reduced numbers and function of immune cells and impaired antigen-specific antibody responses. We studied T cell function in septic mice using cecal ligation and puncture (CLP) as a clinically relevant mouse model for sepsis. The proliferative response of CD4(+) and CD8(+) T cells was suppressed in septic mice. Adoptive transfer experiments demonstrated that the T cells were not intrinsically altered by CLP. Instead, the septic host environment was responsible for this T cell suppression. While CLP-induced suppression was dependent on TNF activity, neither the activation of TNF receptors type 1 nor TNF receptor type 2 alone was sufficient to generate sepsis-induced suppression showing that the two TNF receptors can substitute each other. Specific depletion of regulatory T (Treg) cells improved the impaired T cell proliferation in septic recipients demonstrating participation of Treg in sepsis-induced suppression. In summary, sepsis leads to TNF-dependent suppression of T cell proliferation in vivo involving induction of Treg cells.

Hypogammaglobulinemia and impaired antibody response in a child with chromosome 2p15-16.1 microdeletion syndrome

Immune defects occur at an increased incidence in patients with dysmorphic conditions, with abnormal immunologic laboratory profiles observed in up to 79% of patients with chromosomal disorders. [1] Mahmoud S.A. Lowery-Nordberg M. Chen H. Thurmon T. Ursin S. Bahna S.L. Immune defects in subjects with dysmorphic disorders. Allergy Asthma Proc. 2005; 26: 373-381 PubMed Google Scholar Chromosome 2p15-16.1 microdeletion syndrome is a rare genetic syndrome characterized by dysmorphic facial features with multiple associated anomalies, including intellectual disability with developmental delay, autism spectrum disorder, feeding difficulties, postnatal growth failure, and gastrointestinal complications. 2 Hucthagowder V. Liu T.C. Paciorkowsi A.R. et al. Chromosome 2p15p16.1 microdeletion syndrome: 2.5 Mb deletion in a patient with renal anomalies, intractable seizures and a choledochal cyst. Eur J Med Genet. 2012; 55: 485-489 Crossref PubMed Scopus (15) Google Scholar , 3 Jorgez C.J. Rosenfeld J.A. Wilken N.R. et al. Genitourinary defects associated with genomic deletions in 2p15 encompassing OTX1. PLoS One. 2014; 9: e107028 Crossref PubMed Scopus (24) Google Scholar , 4 de Leeuw N. Pfundt R. Koolen D.A. et al. A newly recognised microdeletion syndrome involving 2p15p16.1: narrowing down the critical region by adding another patient detected by genome wide tiling path array comparative genomic hybridisaion analysis. J Med Genet. 2008; 45: 122-124 Crossref PubMed Scopus (41) Google Scholar , 5 Rajcan-Separovic E. Harvard C. Liu X. et al. Clinical and molecular cytogenetic characterisation of a newly recognised microdeletion syndrome involving 2p15-16.1. J Med Genet. 2007; 44: 269-276 Crossref PubMed Scopus (109) Google Scholar Several patients with this microdeletion syndrome have also presented with recurrent infections, including otitis media, upper respiratory tract infections, and pneumonia. 2 Hucthagowder V. Liu T.C. Paciorkowsi A.R. et al. Chromosome 2p15p16.1 microdeletion syndrome: 2.5 Mb deletion in a patient with renal anomalies, intractable seizures and a choledochal cyst. Eur J Med Genet. 2012; 55: 485-489 Crossref PubMed Scopus (15) Google Scholar , 3 Jorgez C.J. Rosenfeld J.A. Wilken N.R. et al. Genitourinary defects associated with genomic deletions in 2p15 encompassing OTX1. PLoS One. 2014; 9: e107028 Crossref PubMed Scopus (24) Google Scholar , 4 de Leeuw N. Pfundt R. Koolen D.A. et al. A newly recognised microdeletion syndrome involving 2p15p16.1: narrowing down the critical region by adding another patient detected by genome wide tiling path array comparative genomic hybridisaion analysis. J Med Genet. 2008; 45: 122-124 Crossref PubMed Scopus (41) Google Scholar , 5 Rajcan-Separovic E. Harvard C. Liu X. et al. Clinical and molecular cytogenetic characterisation of a newly recognised microdeletion syndrome involving 2p15-16.1. J Med Genet. 2007; 44: 269-276 Crossref PubMed Scopus (109) Google Scholar However, immunodeficiency has not been previously reported in patients with this syndrome. We describe a patient with chromosome 2p15-16.1 microdeletion syndrome and recurrent childhood infections, hypogammaglobulinemia, and impaired vaccine responses successfully treated with immunoglobulin replacement therapy.

Fatal Coxsackie meningoencephalitis in a patient with B-cell lymphopenia and hypogammaglobulinemia following rituximab therapy

Fatal Coxsackie meningoencephalitis in a patient with B-cell lymphopenia and hypogammaglobulinemia following rituximab therapy

CD6 is a novel positive regulator of natural antibody producing B-1a cells (INC1P.401)

Abstract Although CD6 has recently been identified as a risk gene for multiple sclerosis, its biological function remains unclear, partially due to the lack of CD6 gene engineered animals. It is established that CD6 is present on all T cells in both humans and mice; however, it is believed that mouse B cells do not express CD6. B-1a B cells are the primary source of natural antibodies (Nabs), which provide the first line of defense against infection and facilitate the clearance of oxidized lipoproteins that contribute to the pathogenesis of atherosclerosis. By studying CD6 knockout (KO) and WT mice, we found that CD6 is basally expressed selectively on splenic B-1a B cells. CD6 KO mice exhibit smaller B1a B cell population in the spleen concomitant with lower titers of Nabs in the serum than those in WT mice. Interestingly, B-1a-cell-specified progenitors also express CD6 and the frequencies of these progenitors are significantly reduced in the CD6 KO mice. B cell receptor (BCR) signaling is critical for B1a B cell development and T-independent immunoglobulin response. CD6 KO B1a B cells displayed impaired BCR-induced JNK activation and elicited impaired T-independent antibody responses to NP-Ficoll. These findings suggest a positive role for CD6 in regulating B1a B cell homeostasis and immune response.

Manipulation of B-cell responses with histone deacetylase inhibitors.

Histone deacetylase inhibitors (HDACi) are approved for treating certain haematological malignancies, however, recent evidence also illustrates they are modulators of the immune system. In experimental models, HDACi are particularly potent against malignancies originating from the B-lymphocyte lineage. Here we examine the ability of this class of compounds to modify both protective and autoimmune antibody responses. In vitro, HDACi affect B-cell proliferation, survival and differentiation in an HDAC-class-dependent manner. Strikingly, treatment of lupus-prone Mrl/lpr mice with the HDACi panobinostat significantly reduces autoreactive plasma-cell numbers, autoantibodies and nephritis, while other immune parameters remain largely unaffected. Immunized control mice treated with panobinostat or the clinically approved HDACi vorinostat have significantly impaired primary antibody responses, but these treatments surprisingly spare circulating memory B cells. These studies indicate that panobinostat is a potential therapy for B-cell-driven autoimmune conditions and HDACi do not induce major long-term detrimental effects on B-cell memory.

927 End to End VS Side to Side Anastomosis and Post-Operative Crohn's Disease Quality of Life and Healthcare Utilization: A Prospective Comparative Effectiveness Study

tion antibody concentration than those vaccinated with PPV23 (PCV13 2.32 ±2.38; PPV23 1.53 ±1.69; p=0.02). Furthermore, when CD patients were stratified by treatment, vaccination with PCV13 resulted in a higher GM antibody response than vaccination with PPV23 in all groups (ID odds ratio (OR) 1.16, 95% CI 1.01-1.41; ID+TNFαOR 1.17, 95% CI 0.761.95; none OR 1.11, 95% CI 1.03-1.24). Vaccination with PCV13 in patients without immunosuppression resulted in a significantly higher GM value compared to any of the other groups, p<0.01. Conclusion PCV13 induced an overall higher antibody response than PPV23 when vaccinating CD patients. In addition, CD patients treated with ID alone or in combination with TNF-α had an impaired antibody response compared to patients not receiving any of these treatments.

Myelodysplastic Syndrome (MDS) and Acute Lymphocytic Leukemia in Common Variable Immunodeficiency (CVID)

Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia, impaired antibody responses and an increased suspectibility to infections. It is also associated with other diseases of immune dysregulation including autoimmune disease and malignancy, particularly non-Hodgkin lymphomas. However, few cases of myelodysplastic syndrome (MDS) and acute leukemias associated with CVID have been described.

H7N9 influenza virus infection in BALB/c mouse induced impaired neutralizing antibody responses

H7N9 influenza virus infection in BALB/c mouse induced impaired neutralizing antibody responses

Common variable immunodeficiency (CVID): new genetic insight and unanswered questions.

Common variable immunodeficiency (CVID): new genetic insight and unanswered questions.

Chronic helminth infections impair pneumococcal vaccine responses

Pneumonia is the leading killer of children and disproportionately affects developing countries. Vaccination campaigns against Streptococcus pneumoniae, the leading cause of pneumonia, have recently been launched with a new conjugate vaccine in Africa. Using a mouse model, we assessed the potential role that the high burden of helminth infections in the countries targeted for vaccine might have on vaccine effectiveness. Mice vaccinated with either commercial conjugate or purified polysaccharide vaccines had impaired antibody responses if they were chronically infected with Taenia crassiceps. This translated to increased susceptibility to pneumococcal pneumonia and high mortality compared to helminth-negative vaccinated animals, which were fully protected from disease and death. Antibodies taken from Taenia-infected, vaccinated mice were unable to effectively opsonize S. pneumoniae for killing by alveolar macrophages, and did not protect against pneumococcal challenge when adoptively transferred into naïve animals. These data may have implications for vaccination programs in countries endemic with helminths.