scholarly journals Priming for Immunologic Memory in Adults by Meningococcal Group C Conjugate Vaccination

2006 ◽  
Vol 13 (6) ◽  
pp. 605-610 ◽  
Author(s):  
David M. Vu ◽  
Alberdina W. de Boer ◽  
Lisa Danzig ◽  
George Santos ◽  
Bridget Canty ◽  
...  

ABSTRACT Meningococcal group C polysaccharide-protein conjugate vaccines (MCV) prime infants and children for memory anticapsular responses upon subsequent exposure to unconjugated polysaccharide. The objective of this study was to determine whether MCV primes vaccine-naïve adults and adults previously vaccinated with meningococcal polysaccharide vaccine (MPSV) for memory antibody responses. Meningococcal vaccine-naïve adults were randomized to receive either MCV (MCV/naïve group) (n = 35) or pneumococcal conjugate vaccine (PCV) (PCV/naïve group) (n = 34). Participants with a history of receiving MPSV were given MCV (MCV/MPSV group) (n = 26). All subjects were challenged 10 months later with one-fifth of the usual dose of MPSV (10 μg of each polysaccharide). Sera were obtained before the conjugate vaccination and before and 7 days after the MPSV challenge and assayed for immunoglobulin G (IgG) anticapsular antibody concentrations and bactericidal titers. The MCV/naïve group had 7- to 10-fold-higher serum IgG and bactericidal responses after the MPSV challenge than the PCV/naïve group (P < 0.001). The increases (n-fold) in anticapsular antibody concentrations in the MCV/naïve group were greatest in subjects with antibody concentrations of ≤2 μg/ml before the challenge (geometric mean increase [n-fold] of 8.3 versus 1.1 in subjects with concentrations of >2 μg/ml before the challenge; P < 0.0001). Only 3 of 11 MCV-vaccinated subjects who had received MPSV before enrollment and who had antibody concentrations of ≤2 μg/ml before the polysaccharide challenge showed more-than-twofold increases in anticapsular antibody concentration or bactericidal titer after the challenge. MCV vaccination of meningococcal vaccine-naïve adults primes for robust memory antibody responses. There was no evidence of induction of memory by MCV in adults previously vaccinated with MPSV.

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ernesta Cavalcanti ◽  
Maria Antonietta Isgrò ◽  
Domenica Rea ◽  
Lucia Di Capua ◽  
Giusy Trillò ◽  
...  

Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally, requiring the development of billions of different vaccine doses. The SARS-CoV-2 spike mRNA vaccine (named BNT162b2/Pfizer), authorized by the FDA, has shown high efficacy in preventing SARS-CoV-2 infection after administration of two doses in individuals 16 years of age and older. In the present study, we retrospectively evaluated the differences in the SARS-CoV-2 humoral immune response after vaccine administration in the two different cohorts of workers at the INT - IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy): previously infected to SARS-CoV-2 subjects and not infected to SARS-CoV-2 subjects. Methods We determined specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S immunoassay in serum samples of 35 healthcare workers with a previous documented history of SARS-CoV-2 infection and 158 healthcare workers without, after 1 and 2 doses of vaccine, respectively. Moreover, geometric mean titers and relative fold changes (FC) were calculated. Results Both previously infected and not infected to SARS-CoV-2 subjects developed significant immune responses to SARS-CoV-2 after the administration of 1 and 2 doses of vaccine, respectively. Anti-S antibody responses to the first dose of vaccine were significantly higher in previously SARS-CoV-2-infected subjects in comparison to titers of not infected subjects after the first as well as the second dose of vaccine. Fold changes for subjects previously infected to SARS-CoV-2 was very modest, given the high basal antibody titer, as well as the upper limit of 2500.0 BAU/mL imposed by the Roche methods. Conversely, for naïve subjects, mean fold change following the first dose was low ($$ \overline{x} $$ x ¯ =1.6), reaching 3.8 FC in 72 subjects (45.6%) following the second dose. Conclusions The results showed that, as early as the first dose, SARS-CoV-2-infected individuals developed a remarkable and statistically significant immune response in comparison to those who did not contract the virus previously, suggesting the possibility of administering only one dose in previously SARS-CoV-2-infected subjects. FC for previously infected subjects should not be taken into account for the generally high pre-vaccination values. Conversely, FC for not infected subjects, after the second dose, were = 3.8 in > 45.0% of vaccinees, and ≤ 3.1 in 19.0%, the latter showing a potential susceptibility to further SARS-CoV-2 infection.


PEDIATRICS ◽  
1991 ◽  
Vol 88 (3) ◽  
pp. 604-607
Author(s):  
Penelope H. Dennehy ◽  
Keith S. Reisinger ◽  
Mark M. Blatter ◽  
Barbara A. Veloudis

To compare the immunogenicity and safety of varicella vaccine by either subcutaneous or intramuscular injection, 166 healthy children aged 12 months to 10 years old who had no prior history of varicella were enrolled from two pediatric practices and randomly assigned to receive 0.5 mL of a single lot of varicella vaccine. Sera from the day of and 6 weeks postvaccination were tested for varicella antibody by gpELISA. Parents recorded clinical events occurring in the 6 weeks following vaccination. In the 132 evaluable children, the mean prevaccination titer was 0.3 gpELISA units for both groups. Sixty-three (97%) of the 65 receiving varicella vaccine by the subcutaneous route seroconverted compared with 67 (100%) of 67 immunized intramuscularly. Postvaccination geometric mean titer in the subcutaneous group was 6.9 ± 7.0 gpELISA units and did not differ significantly from the geometric mean titer of 10.5 ± 4.4 in the intramuscular group. Varicella vaccine was generally well tolerated by either route; 21% of both groups complained of reactions at the injection site and 7% had a varicella-like rash. Although varicella vaccine is recommended to be given subcutaneously, the results of this study indicate that inadvertent intramuscular administration of varicella vaccine is not reason for revaccination.


2019 ◽  
Vol 104 (7) ◽  
pp. 680-684
Author(s):  
Petra Zimmermann ◽  
Kirsten P Perrett ◽  
Guy Berbers ◽  
Nigel Curtis

IntroductionDespite immunisation, antibiotics and intensive care management, infection with Streptococcus pneumoniae remains a major cause of morbidity and mortality in children. The WHO currently recommends vaccinating infants with either a 3+0 schedule (6 weeks, 3–4 and 4–6 months of age) or 2+1 schedule (2 doses before 6 months of age, plus a booster dose at 9–15 months of age). This study investigated pneumococcal antibody responses, including persistence of antibodies, after immunisation of healthy infants with a 3+0 schedule.MethodsWe measured pneumococcal antibody concentrations to all 13 antigens included in the 13-valent pneumococcal conjugate vaccine (PCV13) after immunisation with a 3+0 schedule in 91 infants at 7 months and in 311 infants at 13 months of age. The geometric mean concentrations (GMCs) and the proportion of infants with an antibody concentration above the standard threshold correlate of protection (seroprotection rate) were calculated at both time points.ResultsAt 7 months of age, GMCs varied between 0.52 µg/mLand 11.52 µg/mL, and seroprotection rates varied between 69% and 100%. At 13 months of age, GMCs had decreased to between 0.22 µg/mLand 3.09 µg/mL, with the lowest responses against serotype 4, followed by 19A, 3, 6B and 23F. Seroprotection rates at 13 months of age were below 90% for most serotypes, with the lowest rates for serotype 4 (23%) followed by 19A (50%), 23F (61%) and 6B (64%).ConclusionOur study shows that at 13 months of age, many infants vaccinated with a 3+0 schedule have pneumococcal antibody concentrations below the standard threshold correlate of protection. To optimise protection against pneumococcal disease through early childhood and to improve antibody persistence and indirect protective effects, immunisation schedules with booster doses might be necessary.


2021 ◽  
Author(s):  
Ernesta Cavalcanti ◽  
Maria Antonietta Isgrò ◽  
Domenica Rea ◽  
Lucia Di Capua ◽  
Giusy Trillò ◽  
...  

Abstract Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally, requiring the development of billions of different vaccine doses. The SARS-CoV-2 spike mRNA vaccine (named BNT162b2/Pfizer), authorized by the FDA, has shown high efficacy in preventing SARS-CoV-2 infection after administration of two doses in individuals 16 years of age and older. In the present study, we retrospectively evaluated the differences in the SARS-CoV-2 humoral immune response after vaccine administration in the two different cohorts of workers at the INT - IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy): previously exposed to SARS-CoV-2 subjects and not exposed to SARS-CoV-2 subjects.Methods: We determined specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S immunoassay in serum samples of 35 healthcare workers with a previous documented history of SARS-CoV-2 infection and 158 healthcare workers without, after 1 and 2 doses of vaccine, respectively. Moreover, geometric mean titers and relative fold changes (FC) were calculated.Results: Both previously exposed and not exposed to SARS-CoV-2 subjects developed significant immune responses to SARS-CoV-2 after the administration of 1 and 2 doses of vaccine, respectively. Anti-S antibody responses to the first dose of vaccine were significantly higher in previously SARS-CoV-2-exposed subjects in comparison to titers of not exposed subjects after the first as well as the second dose of vaccine. Fold changes for subjects previously exposed to SARS-CoV-2 was very modest, given the high basal antibody titer, as well as the upper limit of 2500.0 BAU/mL imposed by the Roche methods. Conversely, for naïve subjects, mean fold change following the first dose was low ( =1.6), reaching 3.8 FC in 72 subjects (45.6%) following the second dose.Conclusions: The results showed that, as early as the first dose, SARS-CoV-2-exposed individuals developed a remarkable and statistically significant immune response in comparison to those who did not contract the virus previously, suggesting the possibility of administering only one dose in previously SARS-CoV-2-exposed subjects. FC for previously exposed subjects should not be taken into account for the generally high pre-vaccination values. Conversely, FC for not exposed subjects, after the second dose, were = 3.8 in >45.0% of vaccinees, and ≤3.1 in 19.0%, the latter showing a potential susceptibility to further SARS-CoV-2 infection.


2000 ◽  
Vol 68 (3) ◽  
pp. 1450-1456 ◽  
Author(s):  
Rose S. Chu ◽  
Tera McCool ◽  
Neil S. Greenspan ◽  
John R. Schreiber ◽  
Clifford V. Harding

ABSTRACT Pneumococcal polysaccharide-protein conjugate vaccines elicit antipolysaccharide antibodies, but multiple doses are required to achieve protective antibody levels in children. In addition, the immunogenicity of experimental multivalent pneumococcal conjugate vaccines varies with different polysaccharide serotypes. One strategy to improve these vaccines is to incorporate an adjuvant to enhance their immunogenicity. Synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) are adjuvants that promote T-cell and T-dependent antibody responses to protein antigens, but it has been unclear whether CpG ODN can enhance polysaccharide-specific antibody responses. The present studies demonstrate significant adjuvant activity of CpG ODN for antibody responses against Streptococcus pneumoniae polysaccharide types 19F and 6B induced by conjugates of 19F and 6B with the protein carrier CRM197. BALB/c ByJ mice were injected with 19F-CRM197 or 6B-CRM197with or without CpG ODN, and sera were tested for anti-19F or anti-6B antibodies by enzyme-linked immunosorbent assay. The polysaccharide-specific antibody response to 19F-CRM197alone was predominantly of the immunoglobulin G1 (IgG1) and IgM isotypes, but addition of CpG ODN markedly increased geometric mean titers of total anti-19F antibody (23-fold), anti-19F IgG2a (26-fold), and anti-19F IgG3 (>246-fold). The polysaccharide-specific antibody response to 6B-CRM197 alone consisted only of IgM, but addition of CpG ODN induced high titers of anti-6B IgG1 (>78-fold increase), anti-6B IgG2a (>54-fold increase), and anti-6B IgG3 (>3,162-fold increase). CpG ODN also increased anti-CRM197IgG2a and IgG3. Adjuvant effects were not observed with control non-CpG ODN. Thus, CpG ODN significantly enhance antipolysaccharide IgG responses (especially IgG2a and IgG3) induced by these glycoconjugate vaccines.


2008 ◽  
Vol 16 (2) ◽  
pp. 194-199 ◽  
Author(s):  
Jo Southern ◽  
Ray Borrow ◽  
Nick Andrews ◽  
Rhonwen Morris ◽  
Pauline Waight ◽  
...  

ABSTRACT This study investigated the use of two doses of three different meningococcal group C conjugate (MCC) vaccines when given for primary immunization with a seven-valent pneumococcal conjugate vaccine (PCV7) and Pediacel, a combination product containing five acellular pertussis components, diphtheria and tetanus toxoids, Haemophilus influenzae type b (Hib) conjugate, and inactivated-poliovirus vaccine. The immune response after a single dose of MCC is also presented. Infants were randomized to receive two doses of one of the MCC vaccines and PCV7 at 2 and 3 months or at 2 and 4 months of age. Meningococcal group C serum bactericidal antibody (SBA) geometric mean titers, Hib-polyribosylribitol phosphate (PRP) immunoglobulin G (IgG) geometric mean concentrations (GMCs), and diphtheria and tetanus antitoxin GMCs, together with the proportions of infants achieving putative protective levels, were determined. A total of 393 infants were recruited. Following the first dose of NeisVac-C (MCC conjugated to tetanus toxoid), 97% of infants achieved protective levels (SBA titer of ≥8), compared with 80% and 53%, respectively, for Menjugate and Meningitec (both of which are conjugated to CRM197). SBA responses to MCC vaccines were not significantly different when administered at 2 and 3 or 2 and 4 months of age. Following two doses of each MCC, 98 to 100% of infants achieved protective levels. Both PRP IgG and tetanus responses were significantly enhanced when Pediacel was coadministered with NeisVac-C. This study demonstrates that NeisVac-C and Menjugate generate good immunogenicity after the first dose at 2 months of age when coadministered with PCV7 and Pediacel and merit further investigation in single-dose priming strategies.


2001 ◽  
Vol 40 (04) ◽  
pp. 107-110 ◽  
Author(s):  
B. Roßmüller ◽  
S. Alalp ◽  
S. Fischer ◽  
S. Dresel ◽  
K. Hahn ◽  
...  

SummaryFor assessment of differential renal function (PF) by means of static renal scintigraphy with Tc-99m-dimer-captosuccinic acid (DMSA) the calculation of the geometric mean of counts from the anterior and posterior view is recommended. Aim of this retrospective study was to find out, if the anterior view is necessary to receive an accurate differential renal function by calculating the geometric mean compared to calculating PF using the counts of the posterior view only. Methods: 164 DMSA-scans of 151 children (86 f, 65 m) aged 16 d to 16 a (4.7 ± 3.9 a) were reviewed. The scans were performed using a dual head gamma camera (Picker Prism 2000 XP, low energy ultra high resolution collimator, matrix 256 x 256,300 kcts/view, Zoom: 1.6-2.0). Background corrected values from both kidneys anterior and posterior were obtained. Using region of interest technique PF was calculated using the counts of the dorsal view and compared with the calculated geometric mean [SQR(Ctsdors x Ctsventr]. Results: The differential function of the right kidney was significantly less when compared to the calculation of the geometric mean (p<0.01). The mean difference between the PFgeom and the PFdors was 1.5 ± 1.4%. A difference > 5% (5.0-9.5%) was obtained in only 6/164 scans (3.7%). Three of 6 patients presented with an underestimated PFdors due to dystopic kidneys on the left side in 2 patients and on the right side in one patient. The other 3 patients with a difference >5% did not show any renal abnormality. Conclusion: The calculation of the PF from the posterior view only will give an underestimated value of the right kidney compared to the calculation of the geometric mean. This effect is not relevant for the calculation of the differntial renal function in orthotopic kidneys, so that in these cases the anterior view is not necesssary. However, geometric mean calculation to obtain reliable values for differential renal function should be applied in cases with an obvious anatomical abnormality.


Author(s):  
Aditi Dey ◽  
Han Wang ◽  
Helen Quinn ◽  
Rona Hiam ◽  
Nicholas Wood ◽  
...  

This report summarises Australian passive surveillance data for adverse events following immunisation (AEFI) for 2017 reported to the Therapeutic Goods Administration and describes reporting trends over the 18-year period 1 January 2000 to 31 December 2017. There were 3,878 AEFI records for vaccines administered in 2017; an annual AEFI reporting rate of 15.8 per 100,000 population. There was a 12% increase in the overall AEFI reporting rate in 2017 compared with 2016. This increase in reported adverse events in 2017 compared to the previous year was likely due to the introduction of the zoster vaccine (Zostavax®) provided free for people aged 70–79 years under the National Immunisation Program (NIP) and also the state- and territory-based meningococcal ACWY conjugate vaccination programs. AEFI reporting rates for most other individual vaccines in 2017 were similar to 2016. The most commonly reported reactions were injection site reaction (34%), pyrexia (17%), rash (15%), vomiting (8%) and pain (7%). The majority of AEFI reports (88%) described non-serious events. Two deaths were reported that were determined to have a causal relationship with vaccination; they occurred in immunocompromised people contraindicated to receive the vaccines.


2003 ◽  
Vol 37 (2) ◽  
pp. 202-205 ◽  
Author(s):  
Patrick G Clay ◽  
Molly M Adams

OBJECTIVE: To report a case of Parkinson-like symptoms appearing in a patient after introduction of ritonavir to buspirone therapy. CASE SUMMARY: A 54-year-old HIV-positive white man presented to the clinic with a 2-week history of ataxia, shuffling gait, cogwheel rigidity, resting tremor, and sad affect with masked features. This patient had been receiving high-dose buspirone (40 mg every morning and 30 mg every evening) for 2 years prior to the introduction of ritonavir/indinavir combination therapy (400 mg/400 mg twice daily) 6 weeks prior to initiation of the above symptoms. Buspirone was decreased to 15 mg 3 times daily, ritonavir/indinavir was discontinued, and amprenavir 1200 mg twice daily was added. The patient's symptoms began to subside after 1 week, with complete resolution after about 2 weeks. The patient continued to receive buspirone for an additional 12 months without recurrence of symptoms. DISCUSSION: This is the first reported interaction of buspirone and antiretrovirals. Buspirone, extensively metabolized by CYP3A4, was likely at supratherapeutic levels due to the inhibitory effect of ritonavir and, secondarily, indinavir. The Parkinson-like symptoms developed rapidly and severely, impacted this patient's quality of life, and necessitated significant clinic expenditures to identify this drug–drug interaction. CONCLUSIONS: This case demonstrates a severe drug–drug interaction between buspirone and ritonavir and further demonstrates the need for awareness of the metabolic profile for all agents an HIV-infected patient is receiving.


2021 ◽  
Vol 7 (15) ◽  
pp. eabf6780
Author(s):  
Corinde E. Wiers ◽  
Leandro F. Vendruscolo ◽  
Jan-Willem van der Veen ◽  
Peter Manza ◽  
Ehsan Shokri-Kojori ◽  
...  

Individuals with alcohol use disorder (AUD) show elevated brain metabolism of acetate at the expense of glucose. We hypothesized that a shift in energy substrates during withdrawal may contribute to withdrawal severity and neurotoxicity in AUD and that a ketogenic diet (KD) may mitigate these effects. We found that inpatients with AUD randomized to receive KD (n = 19) required fewer benzodiazepines during the first week of detoxification, in comparison to those receiving a standard American (SA) diet (n = 14). Over a 3-week treatment, KD compared to SA showed lower “wanting” and increased dorsal anterior cingulate cortex (dACC) reactivity to alcohol cues and altered dACC bioenergetics (i.e., elevated ketones and glutamate and lower neuroinflammatory markers). In a rat model of alcohol dependence, a history of KD reduced alcohol consumption. We provide clinical and preclinical evidence for beneficial effects of KD on managing alcohol withdrawal and on reducing alcohol drinking.


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