PMID- 29132988
OWN - NLM
STAT- MEDLINE
DCOM- 20180731
LR  - 20231115
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Linking)
VI  - 35
IP  - 51
DP  - 2017 Dec 18
TI  - Safety and immunogenicity of a novel multiple antigen pneumococcal vaccine in 
      adults: A Phase 1 randomised clinical trial.
PG  - 7181-7186
LID - S0264-410X(17)31484-6 [pii]
LID - 10.1016/j.vaccine.2017.10.076 [doi]
AB  - BACKGROUND: Pneumococcal vaccines, combining multiple protein antigens, provide 
      an alternative approach to currently marketed vaccines and may provide broader 
      protection against pneumococcal disease. This trial evaluated the safety and 
      immunogenicity of a novel vaccine candidate PnuBioVax in healthy young adults. 
      METHODS: In a Phase 1 double-blind study, 36 subjects (18-40 years) were 
      randomised to receive 3 doses of PnuBioVax, 28 days apart, at one of three dose 
      levels (50, 200, 500 microg) or placebo. Safety assessments included rates of 
      emergent adverse events (AEs), injection site and systemic reactions. 
      Immunogenicity endpoints included antibody titre against PnuBioVax and selected 
      pneumococcal antigens. RESULTS: In the placebo (n=9) and PnuBioVax (n=27) 
      vaccinated subjects, there were 15 and 72, reported TEAEs, respectively. The 
      majority of TEAEs were classified as common vaccine related AEs. There were no 
      serious AEs. Common vaccine-related AEs occurred in 13 PnuBioVax (48%) and 2 
      placebo (22%) subjects and were all headaches (mild and moderate). Injection site 
      reactions, mostly pain and tenderness (graded mild or moderate) were reported, in 
      particular in the 200 microg and 500 microg PnuBioVax groups. There were no clinically 
      significant changes in vital signs, ECG or blood chemistries. Subjects receiving 
      the higher dose (200 and 500 mug) demonstrated a greater fold increase in IgG 
      titre compared with the starting dose (50 mug) or the placebo group. The 
      fold-increase was statistically significantly higher for 200 and 500microg PnuBioVax 
      vs 50microg PnuBioVax and placebo at each timepoint post-immunisation. Most subjects 
      receiving 200 and 500 microg PnuBioVax demonstrated a >/=2-fold increase in antibody 
      against pneumolysin (Ply), Pneumococcal surface antigen (PsaA), PiaA 
      (Pneumococcal iron acquisition), PspA (Pneumococcal surface protein A) and pilus 
      proteins (RrgB and RrgA). CONCLUSIONS: All dose levels were considered safe and 
      well tolerated. There was a statistically significant increase in anti-PnuBioVax 
      IgG titres at the 200 and 500 microg dose levels compared to 50 microg and placebo. TRIAL 
      REGISTRATION NUMBER: NCT02572635https://www.clinicaltrials.gov.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Entwisle, Claire
AU  - Entwisle C
AD  - ImmunoBiology Ltd, Babraham Research Campus, Cambridge, UK. Electronic address: 
      Claire.Entwisle@Immbio.com.
FAU - Hill, Sue
AU  - Hill S
AD  - ImmunoBiology Ltd, Babraham Research Campus, Cambridge, UK.
FAU - Pang, Yin
AU  - Pang Y
AD  - ImmunoBiology Ltd, Babraham Research Campus, Cambridge, UK.
FAU - Joachim, Michael
AU  - Joachim M
AD  - ImmunoBiology Ltd, Babraham Research Campus, Cambridge, UK.
FAU - McIlgorm, Ann
AU  - McIlgorm A
AD  - ImmunoBiology Ltd, Babraham Research Campus, Cambridge, UK.
FAU - Colaco, Camilo
AU  - Colaco C
AD  - ImmunoBiology Ltd, Babraham Research Campus, Cambridge, UK.
FAU - Goldblatt, David
AU  - Goldblatt D
AD  - Immunobiology Section, UCL GOS Institute of Child Health, London, UK.
FAU - De Gorguette D'Argoeuves, Polly
AU  - De Gorguette D'Argoeuves P
AD  - Immunobiology Section, UCL GOS Institute of Child Health, London, UK.
FAU - Bailey, Chris
AU  - Bailey C
AD  - ImmunoBiology Ltd, Babraham Research Campus, Cambridge, UK.
LA  - eng
SI  - ClinicalTrials.gov/NCT02572635
GR  - G0902176/MRC_/Medical Research Council/United Kingdom
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20171110
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Adhesins, Bacterial)
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Lipoproteins)
RN  - 0 (Pneumococcal Vaccines)
RN  - 0 (PsaA protein, Streptococcus)
RN  - 0 (RrgA protein, Streptococcus pneumoniae)
RN  - 0 (Streptolysins)
RN  - 0 (Virulence Factors)
RN  - 0 (plY protein, Streptococcus pneumoniae)
RN  - 147680-16-8 (Fimbriae Proteins)
SB  - IM
MH  - Adhesins, Bacterial/immunology
MH  - Adult
MH  - Antigens, Bacterial/administration & dosage/*chemistry/*immunology
MH  - Bacterial Proteins/immunology
MH  - Double-Blind Method
MH  - Female
MH  - Fimbriae Proteins/immunology
MH  - Humans
MH  - *Immunogenicity, Vaccine
MH  - Immunoglobulin G/blood
MH  - Lipoproteins/immunology
MH  - Male
MH  - Pneumococcal Vaccines/administration & dosage/*adverse 
      effects/chemistry/*immunology
MH  - Streptococcus pneumoniae/immunology
MH  - Streptolysins/immunology
MH  - Vaccination
MH  - Virulence Factors/immunology
MH  - Young Adult
OTO - NOTNLM
OT  - Immunogenicity
OT  - Multiple antigen vaccine
OT  - Phase I
OT  - Pneumococcal infection
OT  - PnuBioVax
OT  - Safety
EDAT- 2017/11/15 06:00
MHDA- 2018/08/01 06:00
CRDT- 2017/11/15 06:00
PHST- 2017/08/31 00:00 [received]
PHST- 2017/10/23 00:00 [revised]
PHST- 2017/10/24 00:00 [accepted]
PHST- 2017/11/15 06:00 [pubmed]
PHST- 2018/08/01 06:00 [medline]
PHST- 2017/11/15 06:00 [entrez]
AID - S0264-410X(17)31484-6 [pii]
AID - 10.1016/j.vaccine.2017.10.076 [doi]
PST - ppublish
SO  - Vaccine. 2017 Dec 18;35(51):7181-7186. doi: 10.1016/j.vaccine.2017.10.076. Epub 
      2017 Nov 10.