PMID- 35118580
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2193-8229 (Print)
IS  - 2193-6382 (Electronic)
IS  - 2193-6382 (Linking)
VI  - 11
IP  - 2
DP  - 2022 Apr
TI  - GMMA Technology for the Development of Safe Vaccines: Meta-Analysis of Individual 
      Patient Data to Assess the Safety Profile of Shigella sonnei 1790GAHB Vaccine in 
      Healthy Adults, with Special Focus on Neutropenia.
PG  - 757-770
LID - 10.1007/s40121-022-00596-x [doi]
AB  - INTRODUCTION: Shigellosis is a major health concern among children < 5 years of 
      age from developing countries, and there are no widely available vaccines to 
      prevent it. The GMMA-based 1790GAHB investigational vaccine against Shigella 
      sonnei was well tolerated and immunogenic in phase 1 and 2 studies conducted in 
      healthy adults from Shigella endemic and non-endemic populations. Based on pooled 
      data of five individual trials, we assessed the association between vaccine 
      administration and the risk of neutropenia as well as the overall safety profile 
      of 1790GAHB. METHODS: The risk ratio (RR) of neutropenia was evaluated between 
      participants receiving 1790GAHB (vaccinees) and active comparator/placebo 
      (controls) using different ethnicity-specific absolute neutrophil count (ANC) 
      thresholds established to define neutropenia. Safety was assessed in terms of 
      solicited, unsolicited, and serious adverse events (AEs). RESULTS: Of the 279 
      participants, 11 (5.5%) vaccinees and 4 (5.0%) controls had ANC below the 
      appropriate threshold within 7 days post-vaccination. RR was 0.96 [95% confidence 
      interval (CI) 0.54-1.70]. When neutrophil counts of participants of African 
      descent were measured against an ethnicity non-specific threshold, they resulted 
      in neutropenia episodes in 30 (37.0%) vaccinees and 16 (30.2%) controls, while 
      only 2 (2.5%) vaccinees and 1 (1.9%) control had neutropenia when the 
      ethnicity-specific threshold was applied. RRs were 0.98 (95% CI 0.75-1.28) and 
      1.30 (95% CI 0.1-17.6), respectively. Solicited and unsolicited AEs were slightly 
      more frequent among vaccinees than controls. No serious AEs, other than 
      neutropenia cases, were recorded in the vaccine group. CONCLUSION: By applying 
      the appropriate threshold, no increased risk of neutropenia was identified in 
      vaccinees compared with the controls. The frequency of neutropenia events varied 
      drastically when ethnicity-appropriate thresholds were applied. This observation 
      highlights the importance of selecting appropriate cut-off values according to 
      the correct population reference. Overall, the 1790GAHB vaccine demonstrated an 
      acceptable safety profile.
CI  - (c) 2022. The Author(s).
FAU - De Ryck, Iris
AU  - De Ryck I
AUID- ORCID: 0000-0003-3044-1117
AD  - GSK, Siena, Italy. iris.x.de-ryck@gsk.com.
FAU - Sarakinou, Eleanna
AU  - Sarakinou E
AD  - GSK Vaccines Institute for Global Health, Via Fiorentina 1, 53100, Siena, Italy.
FAU - Nakakana, Usman
AU  - Nakakana U
AD  - GSK Vaccines Institute for Global Health, Via Fiorentina 1, 53100, Siena, Italy.
FAU - Cilio, Giulia Luna
AU  - Cilio GL
AD  - GSK, Siena, Italy.
FAU - Ndiaye, Augustin
AU  - Ndiaye A
AD  - Takeda Pharmaceutical International AG, Zurich, Switzerland.
FAU - Vella, Venanzio
AU  - Vella V
AD  - GSK, Siena, Italy.
FAU - Auerbach, Joachim
AU  - Auerbach J
AD  - GSK Vaccines Institute for Global Health, Via Fiorentina 1, 53100, Siena, Italy.
AD  - Coalition for Epidemic Preparedness Innovations, London, UK.
FAU - Granada, Juan-Paolo
AU  - Granada JP
AD  - Ferring Pharmaceuticals, Copenhagen, Denmark.
FAU - Conti, Valentino
AU  - Conti V
AD  - GSK Vaccines Institute for Global Health, Via Fiorentina 1, 53100, Siena, Italy.
FAU - Podda, Audino
AU  - Podda A
AD  - GSK Vaccines Institute for Global Health, Via Fiorentina 1, 53100, Siena, Italy.
LA  - eng
PT  - Journal Article
DEP - 20220203
PL  - New Zealand
TA  - Infect Dis Ther
JT  - Infectious diseases and therapy
JID - 101634499
EIN - Infect Dis Ther. 2022 Jun;11(3):1313. PMID: 35435576
PMC - PMC8960504
OTO - NOTNLM
OT  - 1790GAHB vaccine
OT  - GMMA technology
OT  - Neutropenia
OT  - Safety profile
OT  - Shigella sonnei
EDAT- 2022/02/05 06:00
MHDA- 2022/02/05 06:01
PMCR- 2022/02/03
CRDT- 2022/02/04 05:55
PHST- 2021/11/26 00:00 [received]
PHST- 2022/01/21 00:00 [accepted]
PHST- 2022/02/05 06:00 [pubmed]
PHST- 2022/02/05 06:01 [medline]
PHST- 2022/02/04 05:55 [entrez]
PHST- 2022/02/03 00:00 [pmc-release]
AID - 10.1007/s40121-022-00596-x [pii]
AID - 596 [pii]
AID - 10.1007/s40121-022-00596-x [doi]
PST - ppublish
SO  - Infect Dis Ther. 2022 Apr;11(2):757-770. doi: 10.1007/s40121-022-00596-x. Epub 
      2022 Feb 3.