Pneumococcal Vaccine Responses Research Articles

No Waning of Pneumococcal Vaccine Responses over Time in People with Inflammatory Arthritis: Findings from a Single Centre Cohort.

Vaccination against pneumococcus reduces the risk of infective events, hospitalisation, and death in individual with inflammatory arthritis, particularly in those on immunomodulating therapy who are at risk of worse outcomes from pneumococcal disease. The objective of this study was to investigate the serological protection following vaccination against pneumococcal serovars over time. Methods: This was a single centre, retrospective cohort study of individuals with rheumatoid arthritis, psoriatic arthritis, or axial spondylarthritis who had previously received the PPSV23 polysaccharide pneumococcal vaccine (Pneumovax). Data were retrieved between January 2021 to August 2023. Dates of previous pneumococcal vaccination were identified using linked primary care records. Serum serotype levels were collected. The primary outcome was serological response defined as a titre ≥0.35 mcg/mL in at least five from a total of 12 evaluated pneumococcal serovars, examined using a Luminex platform. Multivariate logistic regression models adjusting for age, gender, ethnicity, co-morbidities, and the use of prednisolone, conventional synthetic and biological DMARDs were used to determine the odds of a sustained serological response according to time categorised into ≤5 years, 5-10 years, and ≥10 years since vaccination. Results: Serological response was measured in 296 individuals with inflammatory arthritis, with rheumatoid arthritis the most common diagnosis (74% of patients). The median time between pneumococcal vaccine administration and serological assessment was 6 years (interquartile range 2.4 to 9.9). A positive serological response to at least 5 serovars was present in 195/296 (66%) of patients. Time since vaccination did not significantly associate with serological protection compared with those vaccinated <5 years, the adjusted ORs of vaccine response was 1.15 (95% CI 0.64 to 2.07) in those 5-10 years and 1.26 (95% CI: 0.64 to 2.48) in those vaccinated over 10 years ago. No individual variable from the multivariate model reached statistical significance as an independent predictor of vaccine response, although steroid use at the time of vaccine had a consistent detrimental impact on serological immunity. Conclusions: We demonstrated that antibody titres following vaccination against pneumococcal serovars do not appear to wane over time. It appears more critical to focus on maximising the initial vaccine response, which is known to be diminished in this patient population.

Immunogenicity of the Currently Recommended Pneumococcal Vaccination Schedule in Patients with Chronic Lymphocytic Leukaemia

Background Patients with chronic lymphocytic leukemia (CLL) are at increased risk of both invasive pneumococcal disease (IPD) and community acquired pneumonia (CAP) caused by Streptococcus pneumoniae. Therefore, international guidelines recommend pneumococcal vaccination for all CLL patients, preferably before initiation of treatment. The vaccination schedule recommended in the European Conference on Infections in Leukaemia (ECIL) 7 guideline consists of Prevnar13®, a 13-valent pneumococcal conjugated vaccine (PCV13) followed 2 months later by Pneumovax23®, a 23-valent polysaccharide vaccine (PPSV23). However, the immunogenicity of this sequential pneumococcal vaccination schedule in CLL patients is unknown. The aim of this study is to assess the immunogenicity of PCV13 followed by PPSV23 in untreated and treated CLL patients, as CLL treatment has been shown to be a major determinant of COVID-19 vaccine immunogenicity. Methods We quantified pneumococcal immunoglobulin G (IgG) concentrations to 5 pneumococcal serotypes shared across both vaccines (6B, 9V, 14, 19F, 23F) and 4 serotypes unique to PPSV23 (8, 15B, 20, 33F) before and 4-8 weeks after vaccination using a validated multiplex immunoassay, Luminex®. The primary outcome was the serologic response rate (SRR), defined as a ≥4-fold increase in ≥70% of the serotype-specific anti-pneumococcal IgGs. Secondary outcome was serologic protection, defined as an antibody concentration of ≥1.3 mcg/ml for ≥70% of all measured serotypes, in accordance with the definition by the American Academy of Allergy, Asthma & Immunology. Additional secondary outcomes were serotype-specific serologic protection and IgG level dynamics. Results We included 113 CLL patients (mean age 66 years; 39/113 female) in one academic and six teaching hospitals in the Netherlands. All completed the vaccination and measurement schedule. Median time since CLL diagnosis was 3.6 years. Of the 113 patients 33 had previously received CLL treatment, including rituximab (22 patients), cytotoxic chemotherapy (11), ibrutinib (10) and/or venetoclax (7). Seven patients received intravenous immunoglobulin prior to the vaccinations, while 6 received this during the vaccination scheme. The SRR was 11.5% (15% in untreated and 3% in treated patients) (Table 1). A statistically significant increase in all serotype-specific antibody concentrations was observed after vaccination (p <0.001) (Figure 1). The immunogenicity varied per serotype: the percentage of patients mounting a 4-fold increase was lowest for serotype 20 (16%) and highest for serotype 9V (40%). The serotype-specific anti-pneumococcal IgGs after vaccination were all significantly lower in treated than in previously untreated patients. Nevertheless, treatment status was not statistically significant associated with the SRR. Total IgG concentration prior to vaccination was the only evaluated factor associated with the SRR (OR 5.69; p = 0.008). Serologic protection increased from 1.8% before vaccination to 10.6% after both vaccinations (13.8% in untreated and 3% in treated patients). Serotype-specific protection was highest for serotype 14 and 33F (43.4% of patients obtained a concentration of ≥1.3 mcg/ml) and lowest for serotype 6B (16.8%). Conclusion The serologic response to combined PCV13 and PPSV23 vaccination is impaired in previously treated CLL patients as well as in treatment-naive patients, a contrast with COVID-19 vaccination. These findings emphasize the importance of further investigation into the pneumococcal vaccination response in CLL patients. Since patients with CLL are insufficiently protected after a single dose of PCV13, research should focus on multi-dose PCV schedules with the currently available higher valent T cell dependent conjugate vaccines. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Application of vaccine response in the evaluation of patients with suspected B-cell immunodeficiency: Assessment of responses and challenges with interpretation

Diagnostic vaccination is an integral component in the evaluation of patients suspected to have a B cell or humoral deficiency. Evaluation of antibody production in response to both protein- and polysaccharide-based vaccines aids in distinguishing between specific categories of humoral deficiency. Although assessment of pneumococcal polysaccharide responses is widely available and included in diagnostic guidelines, significant variability still exists in the measurement and interpretation of these responses. Interpretation can also be complicated by age, vaccination history and treatment with immunoglobulin replacement therapy. Despite the challenges and limitations of evaluating pneumococcal polysaccharide vaccine responses, it can provide valuable diagnostic and prognostic information to guide therapeutic intervention. Future efforts are needed to further standardize measurement and interpretation of pneumococcal antibody responses to vaccination and to identify and establish other methods and/or vaccines as alternatives to pneumococcal vaccination to address the challenges in certain patient populations.

The metabolic hormone adiponectin affects the correlation between nutritional status and pneumococcal vaccine response in vulnerable indigenous children.

Almost 200 million children worldwide are either undernourished or overweight. Only a few studies have addressed the effect of variation in nutritional status on vaccine response. We previously demonstrated an association between stunting and an increased post-vaccination 13-valent pneumococcal conjugate vaccine (PCV13) response. In this prospective study, we assessed to what extent metabolic hormones may be a modifier in the association between nutritional status and PCV13 response. Venezuelan children aged 6 weeks to 59 months were vaccinated with a primary series of PCV13. Nutritional status and serum levels of leptin, adiponectin and ghrelin were measured upon vaccination and their combined effect on serum post-vaccination antibody concentrations was assessed by generalized estimating equations multivariable regression analysis. A total of 210 children were included, of whom 80 were stunted, 81 had a normal weight and 49 were overweight. Overweight children had lower post-vaccination antibody concentrations than normal weight children (regression coefficient -1.15, 95% CI -2.22 --0.072). Additionally, there was a significant adiponectin-nutritional status interaction. In stunted children, higher adiponectin serum concentrations were associated with lower post-PCV13 antibody concentrations (regression coefficient -0.19, 95% CI -0.24 --0.14) while the opposite was seen in overweight children (regression coefficient 0.14, 95% CI 0.049-0.22). Metabolic hormones, in particular adiponectin, may modify the effect of nutritional status on pneumococcal vaccine response. These findings emphasize the importance of further research to better understand the immunometabolic pathways underlying vaccine response and enable a future of optimal personalized vaccination schedules.

Dietary Intake and Pneumococcal Vaccine Response Among Children (5-7 Years) in Msambweni Division, Kwale County, Kenya.

BackgroundVaccine and sufficient food availability are key factors for reducing pneumonia outbreaks in sub-Saharan Africa.MethodsIn this study, the 10-valent pneumococcal conjugate vaccine (Synflorix® or PCV10) was administered to a child cohort (5–7 years old, n = 237) in Msambweni, Kenya, to determine relationships between dietary intake, nutritional/socioeconomic status of mothers/caregivers, and vaccine response. 7-day food frequency questionnaire (FFQ), dietary diversity score (DDS) and single 24-h dietary recall were used to address participants' dietary assessment and nutritional status. Individual food varieties were recorded and divided into 9 food groups as recommended by Food and Agriculture Organization. Anthropometric measurements, nasopharyngeal swabs and vaccine administration were performed at the initial visit. Participants were followed 4–8 weeks with a blood draw for pneumococcal IgG titers assessed by Luminex assay.FindingsChronic malnutrition was prevalent in the cohort (15% stunting, 16% underweight). Unbalanced dietary intake was observed, with mean energy intake 14% below Recommended Dietary Allowances (1,822 Kcal) for 5–7 years age range. 72% of the daily energy was derived from carbohydrates, 18% from fats and only 10% from proteins. Poor anthropometric status (stunting/underweight) was associated with low socioeconomic/educational status and younger mother/caregiver age (p < 0.002). Limited intake of essential micronutrients (vitamins A, E, K) and minerals (calcium, potassium) associated with low consumption of fresh fruits, vegetables, and animal source foods (dairy, meat) was observed and correlated with poor vaccine response (p < 0.001). In contrast, children who consumed higher amounts of dietary fiber, vitamin B1, zinc, iron, and magnesium had adequate vaccine response (p < 0.05). Correlation between higher dietary diversity score (DDS), higher Vitamin E, K, Zinc intake and adequate vaccine response was also observed (p < 0.03).InterpretationOverall, this study highlights ongoing food scarcity and malnutrition in Kenya and demonstrates the links between adequate socioeconomic conditions, adequate nutrient intake, and vaccine efficacy.

Do JAK inhibitors affect immune response to COVID-19 vaccination? Data from the MAJIK-SFR Registry.

Do JAK inhibitors affect immune response to COVID-19 vaccination? Data from the MAJIK-SFR Registry.

Anti–SARS-CoV-2 Antibody Responses in Patients With IBD Treated With Biologics: Are We Finding CLARITY?

Anti–SARS-CoV-2 Antibody Responses in Patients With IBD Treated With Biologics: Are We Finding CLARITY?

Impact of Pneumococcal Vaccination on Multiple Myeloma

Background. Streptococcus pneumoniae causes substantial morbidity and mortality from pneumonia, septicaemia and meningitis in myeloma primarilyrelated to severe hypogammaglobulinemia. In immunocompromised patients, pneumococcal vaccination is recommended as primeboost 13-valent conjugated vaccine (Prevnar13 ®) followed by 23-valent Pneumococcal polysaccharide (PS) vaccine (Pneumo23 ®) 1 to 2 months apart. However, there is a paucity of data in multiple myeloma (MM) to validate this approach.We aimed at analyzing subclass and isotype (IgG, IgG2, IgA and IgM) specific responses to pneumococcal vaccination.Method. We have prospectively included 28 NDMM. Serum was collected prior to vaccination and any treatment, then were sequentially collected at day 1 of each further cycle until treatment ended. 15 patients received both vaccinations Prevnar13® and Pneumo23® at the same time and 13 the prime boost. To assess the response to vaccination,VaccZyme™ (Binding Site) PCP anti-PS23 IgG, IgG2, IgA and IgM test was performed on every sample. In parallel, adverse events of infectious type were collected, with a particular attention topneumococcal infections.Results. The median age was 66, the M/F ratio was 0.6. All patients, but one, presented with hypogammaglobulinemia at diagnosis, of whom 21 had severe hypogammaglobulinemia < 4g/L. Serum titers of IgG, IgG2, IgM and IgA anti-PS23 increased for 70%, 85%, 80% and 85% of the patients, respectively following vaccination, within a week response after vaccination for the majority of MM. Overall, 80% of the patient obtained significant antibody titres on at least one subtype and 55% for at least three subtypes. Ten patients underwent ASCT among whom eight had serum collected before and after ASCT. The anti-PS23 geometric mean titers significantly decreased when compared prior and after ASCT for IgG2 (49.4 to 11.7), IgA (56.3 to 2.9) and IgM (55.3 to 10.1) subtypes.Among the 20 patients included into this study, 5 reached CR, 7 VGPR, 4 PR, 3 SD and 1 had PD. Our data showed that pneumococcal vaccine responses occurred independently of the degree of disease control, and thus did not correlate with the depth of response rateSevere infection was observed in 5 patients, including two streptococcus oralis and one streptococcus salivarus septicemia (including one pneumonia and septicemia with S.oralis at diagnosis). No patient has presented Streptococcus pneumoniae infection.Conclusion . Most patients respond to pneumococcal vaccination in MM, independently of depth of hypogammaglobulinemia, vaccine schemas, with no difference according to the disease control. However, there was a clear drop in serum vaccine titers following ASCT. This data tends to confirm that MM can respond to vaccination at diagnosis and relapse, but not if the patients are further immunocompromised with a myeloablative treatment approach. DisclosuresFacon:Amgen, Celgene: Speakers Bureau. Harding:The Binding Site: Employment. Leleu:AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pierre Fabre: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Pneumococcal immunity and PCV13 vaccine response in SOT-candidates and recipients

BackgroundSolid organ transplantation (SOT) candidates and recipients are highly vulnerable to invasive pneumococcal diseases (IPD). Data on which to base optimal immunization recommendations for this population is scant. The national distribution of IPD serotypes led the Swiss Health Authorities to recommend in 2014 one dose of pneumococcal-13-valent-conjugate-vaccine (PCV13), without any subsequent dose of the 23-valent-polysaccharide-pneumococcal-vaccine (PPV23). MethodsThis is a retrospective analysis of pneumococcal immunity using a multiplex binding assay, to assess seroprotection rates against a selection of seven PCV13- and seven PPV23-serotypes in SOT-candidates and recipients evaluated and/or transplanted in 2014/2015 in the University Hospitals of Geneva. Seroprotection was defined as serotype-specific antibody concentration greater than 0.5 mg/l and overall seroprotection when this was achieved for ≥ 6/7 serotypes. ResultsPre-vaccination and at time of transplant sera were available for 35/43 (81%), and 43/43 (100%) SOT-candidates respectively. At listing, 17/35 (49%) SOT-candidates were seroprotected against PCV13 and 21/35 (60%) against PPV23 serotypes. Following one systematic dose of PCV13 at listing, 35/43 (81%) SOT-recipients were seroprotected at day of transplant against PCV13-serotypes and 34/43 (79%) against PPV23 serotypes, compared to 21/41 (51%) and 28/41 (68%) respectively in the controls transplanted in 2013, before the systematic PCV13-vaccination. ConclusionsThe systematic vaccination with PCV13 of all SOT candidates without additional PPV23 is a good strategy as it confers seroprotection against a wide range of pneumococcal serotypes. Indeed, one of five PCV13-vaccinated SOT-candidates was nevertheless not seroprotected at time of transplant, reflecting their partial immune competence, and indicating the need for additional dose of pneumococcal vaccines before transplant.

EASL position paper on the use of COVID-19 vaccines in patients with chronic liver diseases, hepatobiliary cancer and liver transplant recipients

According to a recent World Health Organization estimate, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, which originated in China in 2019, has spread globally, infecting nearly 100 million people worldwide by January 2021. Patients with chronic liver diseases (CLD), particularly cirrhosis, hepatobiliary malignancies, candidates for liver transplantation, and immunosuppressed individuals after liver transplantation appear to be at increased risk of infections in general, which in turn translates into increased mortality. This is also the case for SARS-CoV-2 infection, where patients with cirrhosis, in particular, are at high risk of a severe COVID-19 course. Therefore, vaccination against various pathogens including SARS-CoV-2, administered as early as possible in patients with CLD, is an important protective measure. However, due to impaired immune responses in these patients, the immediate and long-term protective response through immunisation may be incomplete. The current SARS-CoV-2 pandemic has led to the exceptionally fast development of several vaccine candidates. A small number of these SARS-CoV-2 vaccine candidates have already undergone phase III, placebo-controlled, clinical trials in healthy individuals with proof of short-term safety, immunogenicity and efficacy. However, although regulatory agencies in the US and Europe have already approved some of these vaccines for clinical use, information on immunogenicity, duration of protection and long-term safety in patients with CLD, cirrhosis, hepatobiliary cancer and liver transplant recipients has yet to be generated. This review summarises the data on vaccine safety, immunogenicity, and efficacy in this patient population in general and discusses the implications of this knowledge on the introduction of the new SARS-CoV-2 vaccines.

An immune stress test for resilience to aging: Pneumococcal vaccine response.

The idea that the degree of response to physical stress in early life can be used to measure health in later life is a novel approach to better define resilience to aging. To investigate this, middle-age (15 months) mice were stressed by vaccination with a commercial pneumococcal vaccine (Prevnar 13), and 30 days later separated into a high antibody response group and a low antibody response group using Elisa to detect IgG serum antibody levels. After 4 months, mice were evaluated for physiological performance and learning ability. The high antibody response group was able to stay on a rotating rod longer than the low antibody response group and were more quickly able to find the escape hole in a spatial navigation learning task. This observation suggests Prevnar 13 antibody response in midlife could be a useful stress test to predict healthy aging.

IgM Memory B Cell Heterogeneity in Immune Responses to Pneumococcal Vaccination in HIV-positive and Healthy Individuals

Abstract Background: Both normal aging and HIV infection impact B cell functionality and lead to activation of resting B cells, memory cell depletion and altered gene expression. As a result, HIV+ individuals and the elderly fail to demonstrate robust and durable immune responses against pneumococcal polysaccharides. Herein, we assessed altered B cell function in high risk groups by utilizing single cell technology. Methods: HIV-positive individuals with CD4+T cell counts >200 on Antiretroviral Therapy (ART) and HIV-negative individuals age groups 21-40 and 50-65 received pneumococcal vaccination. Serum IgG and IgM PPS-specific antibodies were measured pre- and post-immunization using ELISA method. Evaluation of B cells was performed using flow cytometry and single cell RT-PCR. Results: IgM memory B cells are important players in responding to pneumococcal antigens and are present in reduced quantities in HIV+ and aging HIV- individuals. Single cell analysis of IgM memory B cells demonstrated heterogeneity and identified two unique subpopulations. One of the subpopulations represents B cells with higher expression of TACI and BAFF-R and is more likely to dominate in T-cell independent immune responses. IgD+IgM+memory B cells were present in equal proportions in both subpopulations. Conclusion: Pneumococcal vaccine responses in HIV+ and aging HIV- individuals are multifactorial and largely depend on the abundance and phenotypic characteristics of IgM memory B cells.

Impact of pneumococcal vaccine response on asthma exacerbation frequency in young children.

IntroductionChronic asthma is a heterogeneous disease, and increased eosinophils have been shown to predict increased asthma exacerbations, especially in adults. Recent recommendations suggest the need for supplemental PPV‐23 vaccination in older children with chronic asthma.MethodsTo investigate differences in preschool asthma, our case‐cohort study comprised of 127 children, mean age 47 months (32‐65), with a history of asthma exacerbations requiring more than three courses of systemic steroid bursts and more than six antibiotics courses in the previous year.ResultsAt baseline, mean antibody titer response to Streptococcus pneumoniae was decreased at 2.6 ± 2 out of 14 serotypes, despite prior complete pneumococcal conjugate vaccine (PCV) vaccinations. All children were readministered pneumococcal vaccinations with PCV‐13 booster and/or PPSV‐23. Mean postvaccination pneumococcal vaccine (PV) titer response was 16 ± 5 out of 23 serotypes. After contacting 91 parents/caretakers, 75 responded with less frequency of corticosteroids and antibiotic use for asthma exacerbations after PV. This group had baseline eosinophil counts of 211 ± 36/µL, while those without improvement were significantly higher at 371 ± 123/µL,*P < .05. There were no significant differences (P > .05) between the two groups from other baseline measures including demography or atopic status.ConclusionsThis subset of children with exacerbation‐prone asthma had poor antibody titer response to Streptococcus pneumoniae, even with prior complete PCV‐13 immunization. Identification of low antibody responses to PV serotypes may provide a targeted therapeutic approach to reduce wheezing exacerbations in a precise asthma phenotype in children.

Immunological and Clinical Phenotyping in Primary Antibody Deficiencies: a Growing Disease Spectrum.

Although common variable immunodeficiency (CVID) is considered the most prevalent symptomatic primary antibody deficiency (PAD), there is a population with symptomatic PADs that do not meet criteria for CVID. We analyzed clinical and immunological profiles of patients with different PADs to better understand the differences and similarities between CVID and other PADs. We extracted clinical and laboratory data of patients with PADs from electronic medical records. Patients were categorized into CVID, IgG subclass 2 deficiency (IgG2D), IgG deficiency (IgGD), and specificantibody deficiency (sAbD) based on basal immunoglobulin levels and pneumococcal vaccine responses. We compared clinical and immunological characteristics in these groups. All patients, regardless of PAD types, showed similar frequencies of infections, bronchiectasis, and interstitial lung disease (ILD). Hematopoietic malignancies were more frequently found in the CVID than in the IgG2D, IgGD, and sAbD groups, while the latter groups trended towards an increased frequency of connective tissue diseases (CTD). Low counts of natural killer (NK) cells were associated with malignancy, autoimmunity, and ILD in CVID but not in other PAD groups. Higher frequency of hematopoietic malignancy in CVID than in the other PADs and association of lower NK cell counts with non-infectious complications in CVID suggest a relationship between immune alterations and the development of non-infectious manifestations in PADs.

Pneumococcal 13-valent polysaccharide vaccination (PCV13) response in patients with pulmonary aspergillosis

Background Response to pneumococcal 23-valent polysaccharide vaccine (PPV23) is poor in patients with pulmonary aspergillosis, pneumococcal 13-valent polysaccharide vaccine (PCV13) is believed to be more antigenic. Thus practice at the national aspergillosis centre (NAC), Manchester University NHS foundation trust (MFT) is to give PCV13. However, response to PCV13 has not been studied. Methods We conducted a retrospective, observational study of patients with pulmonary aspergillosis at the NAC, MFT. Patients who had non-protective pre-vaccine levels, and received PCV13 between January-2015 and July-2019 with serology available within 3 months after vaccination were included. Serotype-specific pneumococcal IgG antibodies were quantified for 12 pneumococcal serotypes. Non-protective immunity was defined as pre-vaccine level &lt;0.35μg/mL to &gt; 6 out of 12 serotypes. Protective response was defined as level &gt;1.3μg/mL, or an increase in concentration ≥4-fold for at least 9 of 12 serotypes within 3 months. Results 47 of 144 patients receiving PCV13 had non-protective pre-vaccination levels and repeat serology within 3 months post-vaccination. 52% and 20%, of patients who received 2 and 1 doses (respectively) developed protective immunity; χ2(1)=2.987,p= 0.084. 42.86%, 69.23%, 42.86%, 50%, and 0% of patients with chronic pulmonary aspergillosis (CPA), allergic bronchopulmonary aspergillosis (ABPA), severe asthma with fungal sensitisation, aspergillus bronchitis, and mixed ABPA and CPA developed protective immunity; χ2(4)=6.329,p=0.176. Conclusion Patients with CPA respond poorly to PCV13 compared to ABPA. Response to two doses of PCV13 is comparable to one dose of PPV-231. Patients with pulmonary aspergillosis should receive two doses of PCV13 rather than one dose.

Priming with Prevnar® improves global pneumococcal vaccine responses to Pneumovax® in Asthmatic Adults

Priming with Prevnar® improves global pneumococcal vaccine responses to Pneumovax® in Asthmatic Adults

Defining Polysaccharide Antibody Deficiency: Measurement of Anti-Pneumococcal Antibodies and Anti-Salmonella typhi Antibodies in a Cohort of Patients with Recurrent Infections.

The correlation between different methods for the detection of pneumococcal polysaccharide vaccine (PPV) responses to diagnose specific polysaccharide antibody deficiency (SAD) is poor and the criteria for defining a normal response lack consensus. We previously proposed fifth percentile (p5) values of PPV responses as a new cutoff for SAD. To analyze the association of SAD (determined by either World Health Organization (WHO)-standardized ELISA or multiplex bead-based assay) with abnormal response to Salmonella (S.) typhi Vi vaccination in a cohort of patients with recurrent infections. Ninety-four patients with a clinical history suggestive of antibody deficiency received PPV and S. typhi Vi vaccines. Polysaccharide responses to either 3 or 18 pneumococcal serotypes were measured by either the WHO ELISA or a multiplex in-house bead-based assay. Anti-S. typhi Vi IgG were measured by a commercial ELISA kit. Allohemagglutinins (AHA) were measured by agglutination method. Based on the American Academy of Allergy, Asthma and Immunology (AAAAI) criteria for WHO ELISA, 18/94 patients were diagnosed with SAD and 22/93 based on serotype-specific p5 cutoffs for bead-based assay. The association between the two methods was significant, with 10 subjects showing abnormal response according to both techniques. Abnormal response to S. typhi Vi vaccination was found in 7 patients, 6 of which had SAD. No correlation was found between polysaccharide response and AHA, age, or clinical phenotype. The lack of evidence-based gold standards for the diagnosis of SAD represents a challenge in clinical practice. In our cohort, we confirmed the insufficient correlation between different methods of specific PPV response measurement, and showed that the S. typhi Vi response was not contributive. Caution in the interpretation of results is warranted until more reliable diagnostic methods can be validated.

Focusing on Good Responders to Pneumococcal Polysaccharide Vaccination in General Hospital Patients Suspected for Immunodeficiency. A Decision Tree Based on the 23-Valent Pneumococcal IgG Assay.

Background and Aim: Recently, the 23-valent IgG-assay was suggested as screening assay to identify poor responders to pneumococcal polysaccharide (PnPS)-vaccination with the serotype-specific assay as a second-line test. However, in a low pre-test probability general hospital setting predicting good responders could be more valuable to reduce the number of samples needing serotyping.Methods: Serotype-specific PnPS antibody-assays were performed for suspected immunodeficiency in two Dutch general hospitals (Jeroen Bosch Hospital, 's-Hertogenbosch; Elisabeth Tweesteden Hospital, Tilburg). 23-Valent PnPS antibody-assays were subsequently performed in archived material. Data were analyzed using receiver operating characteristic curves (AUC) and agreement indices (ICC).Results: Sera of 284 patients (348 samples) were included; 23-valent IgG-titres and the corresponding sum of PnPS-serotype specific antibodies showed moderate correlation (ICC = 0.63). In 232 conjugated-pneumococcal-vaccine-naïve patients (270 samples), a random 23-valent IgG-titer could discriminate between samples with and without ≥7/11, ≥7/13, or ≥6/9 pneumococcal serotypes when both cut-off values 0.35 and 1.0 μg/ml were used (AUC 0.86 and 0.92, respectively). All patients with a pre-immunization-titer ≥38.2 μg/ml and/or post-immunization-titer ≥96.1 μg/ml and none with a post-immunization-titer ≤38.5 μg/ml exhibited a good response to PnPS vaccination. Using these breakpoints as screening test to predict good responders, only 24% of patients would require further serotyping, as opposed to 68% if breakpoints to predict poor responders would have been used.Conclusion: In a low pre-test probability setting, the 23-valent IgG-assay proved to be a reliable screening test for good responders in conjugated-pneumococcal-vaccine-naïve patients, reducing the overall number of patient samples needing further serotyping, thus reducing overall costs of pneumococcal vaccination response assessment.

Comparison of pneumococcal vaccination response in children with sickle cell disease: HbSS and HbSC

IntroductionSickle cell disease (SCD) children are at increased risk of invasive pneumococcal disease and rely on penicillin prophylaxis and vaccination for infection prevention. Post-vaccination antibody levels in SCD may wane overtime. HbSC are believed to have better immunological response than HbSS. ObjectiveTo compare antibody response to 23-valent pneumococcal polysaccharide vaccine (PPSV-23) between HbSS and HbSC. MethodsPatients with HbSS (n=33) and HbSC (n=11), aged 7–18 years, were prospectively recruited. Luminex pneumococcal antibody levels were measured for 23-serotypes, after two PPSV-23 doses. ResultsAbsolute median titer for 20 of the 23 serotypes was higher in HbSC than HbSS and significantly higher for serotypes 22 (3.9 vs. 1.6mcg/ml; p=0.039) and 43 (2.9 vs. 0.8mcg/ml; p=0.007). HbSC mounted a better immune anti-pneumococcal response compared to HbSS (≥1.3mcg/ml) for 18 of 23 serotypes, albeit not significant for any of the serotypes. More HbSC (64%) than HbSS (42%) were good vaccine responders (p=0.303). Two of 21 (10%) good vaccine responders and nine of 23 (39%) poor vaccine responders SCD participants subsequently developed acute chest syndrome or pneumonia (p=0.036). None of the HbSC patients developed ACS after receiving PPSV-23. HbSS poor vaccine responders were at increased future recurrence risk for ACS (p=0.003), pneumonia (p=0.036) or both (p=0.011), compared to good vaccine responders. ConclusionHbSC possess better pneumococcal vaccine response than HbSS. Poor vaccine response is concerning for future acute pulmonary events. Current vaccination strategy for SCD sub-types are lacking, therefore further study to evaluate utility of vaccine boosters is necessary.

Evaluation of pneumococcal and tetanus vaccine responses in patients with rheumatoid arthritis receiving baricitinib: results from a long-term extension trial substudy

BackgroundClinical guidelines recommend pneumococcal and tetanus vaccinations in patients with rheumatoid arthritis (RA). Baricitinib is an oral, selective Janus kinase (JAK) 1/JAK 2 inhibitor and is approved for the treatment of moderately to severely active RA in adults in over 50 countries including European countries, the USA, and Japan. This substudy evaluated pneumococcal conjugate and tetanus toxoid vaccine (TTV) responses in patients with RA receiving baricitinib. These vaccines elucidate predominantly T cell-dependent humoral antibody response.MethodsEligible RA patients receiving baricitinib 2 mg or 4 mg with or without concomitant methotrexate (MTX) were enrolled in a phase 3 long-term extension trial (RA-BEYOND; ClinicalTrials.gov, NCT01885078) in USA/Puerto Rico. Patients were vaccinated with 13-serotype pneumococcal conjugate vaccine (PCV-13) and TTV. Primary endpoints were the proportion of patients achieving a satisfactory humoral response for PCV-13 (≥ 2-fold increase in anti-pneumococcal antibody concentrations in ≥ 6 serotypes) and TTV (≥ 4-fold increase in anti-tetanus concentrations) at 5 weeks post-vaccination. Secondary endpoints included humoral responses at 12 weeks and functional responses of serotypes 4, 6B, 14, and 23F (twofold and fourfold increases in opsonic indexes at 5 and 12 weeks).ResultsOf 106 patients with a mean duration of RA of approximately 12 years, 80% were female, 30% were taking corticosteroids, and 89% (N = 94) were taking baricitinib plus MTX; most patients (97% PCV-13/96% TTV) completed the evaluations. Overall, 68% (95% CI 58.4, 76.2) of patients achieved a satisfactory response to PCV-13, 43% (34.0, 52.8) achieved a ≥ 4-fold increase in anti-tetanus concentrations, and 74% (64.2, 81.1) achieved a ≥ 2-fold increase. PCV-13 response was similar for patients taking corticosteroids (71%; 53.4, 83.9) vs those not (67%; 55.2, 76.5). The percentage of sera with a ≥ 2-fold increase in post-vaccination opsonic indexes at week 5 ranged from 47% (serotype 14) to 76% (serotype 6B). Through 12 weeks post-vaccination, seven patients (6.6%) reported injection-site events. There were no deaths during the substudy, and three patients experienced a serious adverse event.ConclusionsApproximately two thirds of patients on long-term baricitinib achieved satisfactory humoral and functional responses to PCV-13 vaccination, while TTV responses were less robust. PCV-13 response was not diminished in those taking concomitant corticosteroids.Trial registrationClinicalTrials.gov, NCT01885078. Registered on 24 June 2013.