scholarly journals Immunogenicity and Reactogenicity of a Reduced Schedule of a 4-component Capsular Group B Meningococcal Vaccine: A Randomized Controlled Trial in Infants

2020 ◽  
Vol 7 (5) ◽  
Author(s):  
Marta Valente Pinto ◽  
Daniel O’Connor ◽  
Ushma Galal ◽  
Elizabeth A Clutterbuck ◽  
Hannah Robinson ◽  
...  

Abstract Background The 4-component capsular group B meningococcal vaccine (4CMenB) was licensed as a 4-dose infant schedule but introduced into the United Kingdom as 3 doses at 2, 4, and 12 months of age. We describe the immunogenicity and reactogenicity of the 2 + 1 schedule in infants. Methods Infants were randomized to receive 4CMenB with routine immunizations (test group) at 2, 4, and 12 months or 4CMenB alone at 6, 8, and 13 months of age (control group). Serum bactericidal antibody (SBA) assay against a serogroup B meningococcal reference strain (44/76-SL), memory B-cell responses to factor H binding protein, Neisseria adhesion protein A, Neisseria heparin binding antigen, Porin A (PorA), and reactogenicity was measured. Results One hundred eighty-seven infants were randomized (test group: 94; control group: 93). In the test group, 4CMenB induced SBA titers above the putative protective threshold (1:4) after primary and booster doses in 97% of participants. Postbooster, the SBA GMT (72.1; 95% confidence interval [CI], 51.7–100.4) was numerically higher than the serum bactericidal antibody geometric mean titre (SBA GMT) determined post–primary vaccination (48.6; 95% CI, 37.2–63.4). After primary immunizations, memory B-cell responses did not change when compared with baseline controls, but frequencies significantly increased after booster. Higher frequency of local and systemic adverse reactions was associated with 4CMenB. Conclusions A reduced schedule of 4CMenB was immunogenic and established immunological memory after booster.

2017 ◽  
Vol 217 (4) ◽  
pp. 572-580 ◽  
Author(s):  
Erin M Scherer ◽  
Robin A Smith ◽  
Joseph J Carter ◽  
Gregory C Wipf ◽  
Daniel F Gallego ◽  
...  

2021 ◽  
Vol 10 (9) ◽  
Author(s):  
Leire de Campos‐Mata ◽  
Sonia Tejedor Vaquero ◽  
Roser Tachó‐Piñot ◽  
Janet Piñero ◽  
Emilie K Grasset ◽  
...  

2010 ◽  
Vol 61 (6) ◽  
pp. 517
Author(s):  
Maheshi Ramasamy ◽  
Elizabeth Clutterbuck ◽  
Jaclyn Bowman ◽  
Matthew D. Snape ◽  
Mushiya Mpelembue ◽  
...  

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Piyawan Kochayoo ◽  
Natthapon Kittisenachai ◽  
Siriruk Changrob ◽  
Kittikorn Wangriatisak ◽  
Fauzi Muh ◽  
...  

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3382-3382
Author(s):  
Peter Allacher ◽  
Christina Hausl ◽  
Aniko Ginta Pordes ◽  
Rafi Uddin Ahmad ◽  
Hartmut J Ehrlich ◽  
...  

Abstract Memory B cells are essential for maintaining long-term antibody responses. They can persist for years even in the absence of antigen and are rapidly re-stimulated to differentiate into antibody-producing plasma cells when they encounter their specific antigen. Previously we demonstrated that ligands for TLR 7 and 9 amplify the differentiation of FVIII-specific memory B cells into anti-FVIII antibody-producing plasma cells at low concentrations of FVIII and prevent the inhibition of memory-B-cell differentiation at high concentrations of FVIII. The modulation of FVIII-specific memory-B-cell responses by agonists for TLR is highly relevant for the design of new immunotherapeutic approaches in patients with FVIII inhibitors because TLR are activated by a range of different viral and bacterial components. Specifically, TLR 7 is triggered by single-stranded RNA derived from viruses and TLR 9 is triggered by bacterial DNA containing unmethylated CpG motifs. We further explored the modulation of FVIII-specific memory-B-cell responses by agonists for TLRs by studying a broad range of concentrations of CpG DNA, a ligand for TLR 9, both in vitro and in vivo using the murine E17 model of hemophilia A. We used CpG-DNA in concentrations ranging from 0.1 to 10,000 ng/ml to study the modulation of FVIII-specific memory-B-cell responses in vitro and verified the specificity of the effects observed by including a blocking agent for TLR 9 and GpC-DNA, a non-stimulating negative control for CpG DNA. Furthermore, we used doses of CpG DNA ranging from 10 to 50,000 ng per dose to study the modulation of FVIII-specific memory-B-cell responses in vivo. E17 hemophilic mice were treated with a single intravenous dose of 200 ng FVIII to stimulate the generation of FVIII-specific memory B cells and were subsequently treated with another dose of FVIII that was given together with CpG DNA. We analyzed titers of anti-FVIII antibodies in the circulation of these mice one week after the second dose of FVIII. Previously we had shown that a single dose of 200 ng FVIII, given intravenously to E17 hemophilic mice, stimulates the formation of FVIII-specific memory B cells but is not sufficient to induce anti-FVIII antibodies that would be detectable in the circulation. Our results demonstrate a biphasic effect of CpG DNA on the re-stimulation of FVIII-specific memory B cells and their differentiation into antibody-producing plasma cells. Both in vitro and in vivo studies show that CpG DNA at high doses inhibits the re-stimulation and differentiation of FVIII-specific memory B cells. However, CpG DNA at low doses amplifies these processes. Amplification and inhibition of memory-B-cell responses are due to specific interactions of CpG DNA with TLR 9. Both effects are blocked by addition of a blocking agent for TLR 9 in vitro. We conclude that triggering of TLR 9 by bacterial DNA has a substantial influence on FVIII-specific memory-B-cell responses. The consequence of TLR 9 triggering can be inhibitory or stimulatory, depending on the actual concentration of the bacterial DNA. Our findings demonstrate the potential modulatory effects of bacterial infections on the regulation of FVIII inhibitor development.


2017 ◽  
Vol 18 (1) ◽  
pp. 102-112 ◽  
Author(s):  
M. Fribourg ◽  
J. Ni ◽  
F. Nina Papavasiliou ◽  
Z. Yue ◽  
P. S. Heeger ◽  
...  

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