Safety, reactogenicity and immunogenicity of two investigational pneumococcal protein-based vaccines: Results from a randomized phase II study in infants

Prymula, Roman; Szenborn, Leszek; Silfverdal, Sven‐Arne; Wysocki, Jacek; Albrecht, Piotr; Traskine, Magali; Gardev, Asparuh; Song, Yue; Borys, Dorota

doi:10.1016/j.vaccine.2017.07.008

Cited by 29 publications

(16 citation statements)

References 29 publications

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“…This study did not reveal any safety concern for 12vPHiD-CV vaccination in young children when compared to PHiD-CV vaccination, the latter being widely assessed in clinical trials and real-life settings. 19 In line with previously reported immunogenicity results for a PHiD-CV booster dose administered following a two-or three-dose primary series in infants, [20][21][22] one dose of either PHiD-CV or 12vPHiD-CV induced robust anamnestic immune responses against PHiD-CV serotypes in toddlers previously primed with three doses of PHiD-CV.…”

Section: Discussionsupporting

confidence: 75%

Safety, reactogenicity, and immunogenicity of a 12-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine in healthy toddlers: results from a phase I, randomized trial

Horn

Behre

Traskine

et al. 2020

Human Vaccines & Immunotherapeutics

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As a stepping stone toward evaluation in infants, the safety and immunogenicity of an investigational 12-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (12vPHiD-CV) was assessed in toddlers. 12vPHiD-CV contains CRM 197 -conjugated capsular polysaccharides of serotypes 6A and 19A in addition to capsular polysaccharides of the 10 serotypes in PHiD-CV. In this phase I, double-blind, multicenter study (NCT01485406) conducted in Germany, 61 healthy toddlers aged 12–23 months previously primed with three PHiD-CV doses were randomized (1:1) to receive one dose of 12vPHiD-CV or PHiD-CV. Safety and reactogenicity of 12vPHiD-CV were assessed in terms of occurrence of grade 3 vaccination-related solicited and unsolicited adverse events (AEs) and vaccination-related serious AEs. Immune responses were evaluated 1 month post-vaccination. Grade 3 solicited local AEs (all considered vaccination-related) were reported for two (6.5%, redness) and three (9.7%, swelling) toddlers in the 12vPHiD-CV group and one (3.4%, swelling) in the PHiD-CV group. Grade 3 vaccination-related solicited general AEs were only reported in the PHiD-CV group. No grade 3 unsolicited or serious AEs were reported. For PHiD-CV serotypes, 100% of toddlers in both groups had antibody concentrations ≥0.2 µg/mL 1 month post-vaccination, and antibody geometric mean concentrations increased from pre-boosting. For serotypes 6A and 19A, antibody responses tended to be higher in the 12vPHiD-CV than the PHiD-CV group. A single dose of 12vPHiD-CV administered in toddlers was well tolerated and no safety concerns were identified. Immune responses were comparable to those induced by PHiD-CV when administered in toddlers previously primed with three doses of PHiD-CV.

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Section: Discussionsupporting

confidence: 75%

Safety, reactogenicity, and immunogenicity of a 12-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine in healthy toddlers: results from a phase I, randomized trial

Horn

Behre

Traskine

et al. 2020

Human Vaccines & Immunotherapeutics

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“…With both vaccines, particularly PCV10, poor opsonophagocytic assay responses to serotype 1 were seen post-primary series, despite strong ELISA responses. This finding was reflected in the two European trials of investigational PCVs, in which 41% and 62% of participants in the PCV10 groups and 61% and 84% in the PCV13 groups had an opsonisation index of at least 8 9, 10. This disconnect between responses measured by opsonophagocytic assay and by ELISA is corrected after the booster dose, providing immunological evidence for the importance of a booster dose in protecting against disease.…”

Section: Discussionmentioning

confidence: 91%

“…A trial from Papua New Guinea compared three doses of PCV10 and PCV13 administered at 1 month, 2 months, and 3 months of age, with immunogenicity data obtained prevaccination, after dose three, and at 9 months of age 8 . Two European trials of investigational next-generation pneumococcal vaccines have included control groups of both PCV10 and PCV13, administered in a 3 + 1 schedule at 2 months, 3 months, 4 months, and 12–15 months of age, with immunogenicity data obtained post-primary series, pre-booster, and post-booster 9, 10. Two other trials with post-primary series immunogenicity data available are registered on ClinicalTrials.gov: a trial from The Gambia of investigational, protein-based pneumococcal vaccines administered in a 3 + 0 schedule that includes both PCV10 and PCV13 control groups (NCT01262872); and a trial from Mexico to evaluate mixed regimens that includes groups that received a two-dose primary series of either PCV10 or PCV13 (NCT01641133).…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity and reactogenicity of ten-valent versus 13-valent pneumococcal conjugate vaccines among infants in Ho Chi Minh City, Vietnam: a randomised controlled trial

Temple

Toàn

Dai

et al. 2019

The Lancet Infectious Diseases

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Summary Background Few data are available to support the choice between the two currently available pneumococcal conjugate vaccines (PCVs), ten-valent PCV (PCV10) and 13-valent PCV (PCV13). Here we report a head-to-head comparison of the immunogenicity and reactogenicity of PCV10 and PCV13. Methods In this parallel, open-label, randomised controlled trial, healthy infants from two districts in Ho Chi Minh City, Vietnam, were randomly allocated (in a 3:3:5:4:5:4 ratio), with use of a computer-generated list, to one of six infant PCV schedules: PCV10 in a 3 + 1 (group A), 3 + 0 (group B), 2 + 1 (group C), or two-dose schedule (group D); PCV13 in a 2 + 1 schedule (group E); or no infant PCV (control; group F). Blood samples were collected from infants between 2 months and 18 months of age at various timepoints before and after PCV doses and analysed (in a blinded manner) by ELISA and opsonophagocytic assay. The trial had two independent aims: to compare vaccination responses between PCV10 and PCV13, and to evaluate different schedules of PCV10. In this Article, we present results pertaining to the first aim. The primary outcome was the proportion of infants with an IgG concentration of at least 0·35 μg/mL for the ten serotypes common to the two vaccines at age 5 months, 4 weeks after the two-dose primary vaccination series (group C vs group E, per protocol population). An overall difference among the schedules was defined as at least seven of ten serotypes differing in the same direction at the 10% level. We also assessed whether the two-dose primary series of PCV13 (group E) was non-inferior at the 10% level to a three-dose primary series of PCV10 (groups A and B). This trial is registered with ClinicalTrials.gov , number NCT01953510 . Findings Of 1424 infants screened between Sept 30, 2013, and Jan 9, 2015, 1201 were allocated to the six groups: 152 (13%) to group A, 149 (12%) to group B, 250 (21%) to group C, 202 (17%) to group D, 251 (21%) to group E, and 197 (16%) to group F. 237 (95%) participants in group C (PCV10) and 232 (92%) in group E (PCV13) completed the primary vaccination series and had blood draws within the specified window at age 5 months, at which time the proportion of infants with IgG concentrations of at least 0·35 μg/mL did not differ between groups at the 10% level for any serotype (PCV10–PCV13 risk difference −2·1% [95% CI −4·8 to −0·1] for serotype 1; −1·3% [–3·7 to 0·6] for serotype 4; −3·4% [–6·8 to −0·4] for serotype 5; 15·6 [7·2 to 23·7] for serotype 6B; −1·3% [–3·7 to 0·6] for serotype 7F; −1·6% [–5·1 to 1·7] for serotype 9V; 0·0% [–2·7 to 2·9] for serotype 14; −2·1% [–5·3 to 0·9] for serotype 18C; 0·0% [–2·2 to 2·3] for serotype 19F; and −11·6% [–18·2 to −4·9] for serotype 23F). At the same timepoint, two doses of PCV13 were non-inferior to three doses of PCV10 for nine of the ten shared serotypes (excluding 6B). Reac...

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“…Numerous toxoid versions of pneumolysin have been proposed as vaccine antigens, both as fusion proteins and as components of multivalent vaccines (27,(32)(33)(34)(35)(36)(37)(38)(39)(40)(41). Therefore, we next sought to determine whether a different pneumolysin toxoid fused to fragments of CbpA would confer a degree of protection similar to that of YLN vaccination.…”

Section: Resultsmentioning

confidence: 99%

A Cross-Reactive Protein Vaccine Combined with PCV-13 Prevents Streptococcus pneumoniae- and Haemophilus influenzae-Mediated Acute Otitis Media

et al. 2019

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Acute otitis media is one of the most common childhood infections worldwide. Currently licensed vaccines against the common otopathogen Streptococcus pneumoniae target the bacterial capsular polysaccharide and confer no protection against nonencapsulated strains or capsular types outside vaccine coverage. Mucosal infections such as acute otitis media remain prevalent, even those caused by vaccine-covered serotypes. Here, we report that a protein-based vaccine, a fusion construct of epitopes of CbpA to pneumolysin toxoid, confers effective protection against pneumococcal acute otitis media for non-PCV-13 serotypes and enhances protection for PCV-13 serotypes when coadministered with PCV-13. Having cross-reactive epitopes, the fusion protein also induces potent antibody responses against nontypeable Haemophilus influenzae and S. pneumoniae, engendering protection against acute otitis media caused by emerging unencapsulated otopathogens. These data suggest that augmenting capsule-based vaccination with conserved, cross-reactive protein-based vaccines broadens and enhances protection against acute otitis media.

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Safety, reactogenicity and immunogenicity of two investigational pneumococcal protein-based vaccines: Results from a randomized phase II study in infants

Abstract: Both PHiD-CV/dPly/PhtD formulations co-administered with DTPa-HBV-IPV/Hib in infants were well-tolerated and immunogenic for dPly and PhtD antigens, while immune responses to serotype-specific, protein D and co-administered antigens did not appear altered in comparison to PHiD-CV group.

Cited by 29 publications

References 29 publications

Safety, reactogenicity, and immunogenicity of a 12-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine in healthy toddlers: results from a phase I, randomized trial

Safety, reactogenicity, and immunogenicity of a 12-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine in healthy toddlers: results from a phase I, randomized trial

Immunogenicity and reactogenicity of ten-valent versus 13-valent pneumococcal conjugate vaccines among infants in Ho Chi Minh City, Vietnam: a randomised controlled trial

A Cross-Reactive Protein Vaccine Combined with PCV-13 Prevents Streptococcus pneumoniae- and Haemophilus influenzae-Mediated Acute Otitis Media

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