Safety and immunogenicity of pneumococcal protein vaccine candidates: Monovalent choline-binding protein A (PcpA) vaccine and bivalent PcpA-pneumococcal histidine triad protein D vaccine

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• 作者：Monica Bologa^a ; ^{monica@mbpharma.ca} ; Thierry Kamtchoua^b ; ^{thierry.kamtchoua@covance.com} ; Robert Hopfer^c ; ^{Robert.Hopfer@sanofipasteur.com} ; Xiaohua Sheng^c ; ^{Xiaohua.Sheng@sanofipasteur.com} ; Bryony Hicks^b ; ^{Bryony.Hicks@sanofipasteur.com} ; Garvin Bixler^c ; ^{Garvin.Bixler@sanofipasteur.com} ; Victor Hou^c ; ^{Victor.Hou@sanofipasteur.com} ; Vildana Pehlic^b ; ^{Vildana.Pehlic@covance.com} ; Tao Yuan^a ; ^{Tao.Yuan@sanofipasteur.com} ; Sanjay Gurunathan^c ; ^{Sanjay.Gurunathan@sanofipasteur.com}
• 关键词：AE ; adverse event ; AR ; adverse reaction ; CI ; confidence interval ; ELISA ; enzyme-linked immunosorbent assay ; EU ; ELISA unit ; GMC ; geometric mean concentration ; IgG ; immunoglobulin G ; IM ; intramuscular ; PcpA ; pneumococcal choline-binding protein A ; PhtD ; pn
• 刊名：Vaccine
• 出版年：2012
• 出版时间：14 December, 2012
• 年：2012
• 卷：30
• 期：52
• 页码：7461-7468
• 全文大小：660 K

文摘

Background

Pneumococcal vaccines based on protein antigens may provide expanded protection against Streptococcus pneumoniae.

Objective

To evaluate safety and immunogenicity in adults of pneumococcal vaccine candidates comprising S. pneumoniae pneumococcal histidine triad protein D (PhtD) and pneumococcal choline-binding protein A (PcpA) in monovalent and bivalent formulations.

Methods

This was a phase I, randomized, observer-blinded, placebo-controlled, step-wise dose-escalation study. Following a pilot safety study in which participants received one intramuscular injection of either aluminum hydroxide (AH)-adjuvanted PcpA (25 ¦Ìg) or PhtD-PcpA (10 ¦Ìg each), participants in the main study received AH-adjuvanted PcpA (25 ¦Ìg), AH-adjuvanted PhtD-PcpA (10, 25, or 50 ¦Ìg each), unadjuvanted PhtD-PcpA (25 ¦Ìg each), or placebo as 2 injections 30 days apart. Assignment of successive dose cohorts was made after blinded safety reviews after each dose level. Safety endpoints included rates of solicited injection site and systemic reactions, unsolicited adverse events (AEs), serious AEs (SAEs), and safety laboratory tests. Immunogenicity endpoints included levels of anti-PhtD and anti-PcpA antibodies (ELISA).

Results

Six adults 18-50 years of age were included in the pilot study and 125 in the main study. No obvious increases in solicited reactions or unsolicited AEs were reported with escalating doses (adjuvanted vaccine) after either injection, or with repeated administration. Adjuvanted vaccine candidates were associated with a higher incidence of solicited reactions (particularly injection site reactions) than unadjuvanted vaccine candidates. However, no SAE or discontinuation due to an AE occurred. Geometric mean concentrations of anti-PhtD IgG and anti-PcpA IgG increased significantly after injection 2 compared with injection 1 at each dose level. No enhancement of immune responses was shown with adjuvanted vaccine candidates compared with the unadjuvanted vaccine candidate. In the dose-escalating comparison, a plateau effect at the 25 ¦Ìg dose was observed as measured by geometric mean concentrations and by fold increases.

Conclusions

Promising safety profiles and immunogenicity of these monovalent and bivalent protein vaccine candidates were demonstrated in an adult population (ClinicalTrials.gov registry no. ).