PMID- 31895881
OWN - NLM
STAT- MEDLINE
DCOM- 20210209
LR  - 20210209
IS  - 1532-0987 (Electronic)
IS  - 0891-3668 (Linking)
VI  - 39
IP  - 4
DP  - 2020 Apr
TI  - A Phase 1 Randomized, Placebo-controlled, Observer-blinded Trial to Evaluate the 
      Safety and Immunogenicity of Inactivated Streptococcus pneumoniae Whole-cell 
      Vaccine in Adults.
PG  - 345-351
LID - 10.1097/INF.0000000000002567 [doi]
AB  - BACKGROUND: Broadly protective pneumococcal vaccines that are affordable for 
      low-resource countries are needed. Streptococcus pneumoniae whole cell vaccine 
      (wSp) is an investigational vaccine that contains killed cells from a 
      nonencapsulated strain of S. pneumoniae (SPn) with aluminum hydroxide adjuvant. 
      Studies in mice demonstrated protection against nasopharyngeal carriage 
      (T-cell-mediated) and invasive pneumococcal disease (antibody-mediated). The aim 
      of this randomized, double-blind, placebo-controlled Phase 1 study was to assess 
      safety, tolerability and immunogenicity of wSp in healthy adults. METHODS: 
      Forty-two participants were randomized into 3 dose cohorts to receive 0.1, 0.3, 
      or 0.6 mg of wSp or saline intramuscularly. Participants received a 3-dose 
      vaccination schedule spaced by 4-week intervals. Postvaccination assessments 
      included solicited reactogenicity events through day 7, blood chemistry and 
      hematology assessments at day 7, and adverse events (AEs) through day 84. 
      Participants were monitored for serum antibody and peripheral blood mononuclear 
      cell cytokine responses to pneumococcal antigens. A 6-month telephone follow-up 
      was completed to assess for any additional AEs. RESULTS: wSp was safe and well 
      tolerated. Reactogenicity was acceptable and no untoward safety signals were 
      observed. wSp elicited potentially clinically significant rises (defined 
      arbitrarily as at least a 2-fold rise) in immunoglobulin G responses to multiple 
      pneumococcal antigens, including pneumococcal surface protein A and pneumolysin. 
      Functional antibody responses were observed with the highest dose of wSp 
      (0.6 mg). Increases in T-cell cytokine responses, including interleukin 17A, were 
      also seen among wSp vaccines. CONCLUSIONS: wSp was safe and well tolerated in 
      healthy US adults, eliciting pneumococcal antigen-specific antibody and T-cell 
      cytokine responses.
FAU - Keech, Cheryl A
AU  - Keech CA
AD  - From the PATH, Seattle, Washington.
AD  - PPD, Wilmington, North Carolina.
FAU - Morrison, Royce
AU  - Morrison R
AD  - Clinical Research Consultancy - Design, Medical Monitoring, DMC/DSMB, Safety 
      Assessment, Seattle, Washington.
FAU - Anderson, Porter
AU  - Anderson P
AD  - Boston Children's Hospital, Division of Infectious Diseases, Boston, 
      Massachusetts.
FAU - Tate, Andrea
AU  - Tate A
AD  - From the PATH, Seattle, Washington.
AD  - PPD, Wilmington, North Carolina.
FAU - Flores, Jorge
AU  - Flores J
AD  - From the PATH, Seattle, Washington.
FAU - Goldblatt, David
AU  - Goldblatt D
AD  - Great Ormond Street Institute of Child Biomedical Research Centre, University 
      College London, London, United Kingdom.
FAU - Briles, David
AU  - Briles D
AD  - Department of Microbiology, University of Alabama at Birmingham, Birmingham, 
      Alabama.
FAU - Hural, John
AU  - Hural J
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington.
FAU - Malley, Richard
AU  - Malley R
AD  - Boston Children's Hospital, Division of Infectious Diseases, Boston, 
      Massachusetts.
FAU - Alderson, Mark R
AU  - Alderson MR
AD  - From the PATH, Seattle, Washington.
LA  - eng
SI  - ClinicalTrials.gov/NCT01537185
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pediatr Infect Dis J
JT  - The Pediatric infectious disease journal
JID - 8701858
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Pneumococcal Vaccines)
RN  - 0 (Vaccines, Inactivated)
SB  - IM
MH  - Adjuvants, Immunologic/administration & dosage
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Bacterial/*blood/immunology
MH  - Cohort Studies
MH  - Double-Blind Method
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Immunization Schedule
MH  - *Immunogenicity, Vaccine
MH  - Immunoglobulin G/blood
MH  - Male
MH  - Pneumococcal Infections/immunology/*prevention & control
MH  - Pneumococcal Vaccines/administration & dosage/*immunology
MH  - Streptococcus pneumoniae
MH  - United States
MH  - Vaccines, Inactivated/immunology
MH  - Young Adult
EDAT- 2020/01/03 06:00
MHDA- 2021/02/10 06:00
CRDT- 2020/01/03 06:00
PHST- 2020/01/03 06:00 [pubmed]
PHST- 2021/02/10 06:00 [medline]
PHST- 2020/01/03 06:00 [entrez]
AID - 00006454-202004000-00018 [pii]
AID - 10.1097/INF.0000000000002567 [doi]
PST - ppublish
SO  - Pediatr Infect Dis J. 2020 Apr;39(4):345-351. doi: 10.1097/INF.0000000000002567.