PMID- 34712047
OWN - NLM
STAT- MEDLINE
DCOM- 20211124
LR  - 20220427
IS  - 1178-2013 (Electronic)
IS  - 1176-9114 (Print)
IS  - 1176-9114 (Linking)
VI  - 16
DP  - 2021
TI  - Robust Immune Response Induced by Schistosoma mansoni TSP-2 Antigen Coupled to 
      Bacterial Outer Membrane Vesicles.
PG  - 7153-7168
LID - 10.2147/IJN.S315786 [doi]
AB  - PURPOSE: The use of adjuvants can significantly strengthen a vaccine's efficacy. 
      We sought to explore the immunization efficacy of bacterial outer membrane 
      vesicles (OMVs) displaying the Schistosoma mansoni antigen, SmTSP-2, through a 
      biotin-rhizavidin coupling approach. The rationale is to exploit the 
      nanoparticulate structure and the adjuvant properties of OMVs to induce a robust 
      antigen-specific immune response, in light of developing new vaccines against S. 
      mansoni. MATERIALS AND METHODS: OMVs were obtained from Neisseria lactamica and 
      conjugated with biotin. The recombinant SmTSP-2 in fusion with the biotin-binding 
      protein rhizavidin (rRzvSmTSP-2) was produced in E. coli and coupled to 
      biotinylated OMVs to generate an OMV complex displaying SmTSP-2 on the membrane 
      surface (OMV:rSmTSP-2). Transmission electron microscopy (TEM) and dynamic light 
      scattering analysis were used to determine particle charge and size. The 
      immunogenicity of the vaccine complex was evaluated in C57BL/6 mice. RESULTS: The 
      rRzvSmTSP-2 protein was successfully coupled to biotinylated OMVs and purified by 
      size-exclusion chromatography. The OMV:rSmTSP-2 nanoparticles showed an average 
      size of 200 nm, with zeta potential around - 28 mV. Mouse Bone Marrow Dendritic 
      Cells were activated by the nanoparticles as determined by increased expression 
      of the co-stimulatory molecules CD40 and CD86, and the proinflammatory cytokines 
      (TNF-alpha, IL-6 and IL-12) or IL-10. Splenocytes of mice immunized with OMV:rSmTSP-2 
      nanoparticles reacted to an in vitro challenge with SmTSP-2 with an increased 
      production of IL-6, IL-10 and IL-17 and displayed a higher number of CD4+ and 
      CD8+ T lymphocytes expressing IFN-gamma, IL-4 and IL-2, compared to mice immunized 
      with the antigen alone. Immunization of mice with OMV:rSmTSP-2 induced a 100-fold 
      increase in specific anti-SmTSP-2 IgG antibody titers, as compared to the group 
      receiving the recombinant rSmTSP-2 protein alone or even co-administered with 
      unconjugated OMV. CONCLUSION: Our results demonstrate that the SmTSP-2 antigen 
      coupled with OMVs is highly immunogenic in mice, supporting the potential 
      effectiveness of this platform for improved antigen delivery in novel vaccine 
      strategies.
CI  - (c) 2021 Barbosa et al.
FAU - Barbosa, Mayra M F
AU  - Barbosa MMF
AUID- ORCID: 0000-0003-3602-1279
AD  - Laboratorio de Desenvolvimento de Vacinas, Instituto Butantan, Sao Paulo, Brazil.
AD  - Programa de Pos-Graduacao Interunidades em Biotecnologia, Universidade de Sao 
      Paulo, Sao Paulo, Brazil.
FAU - Kanno, Alex I
AU  - Kanno AI
AD  - Laboratorio de Desenvolvimento de Vacinas, Instituto Butantan, Sao Paulo, Brazil.
FAU - Barazzone, Giovana C
AU  - Barazzone GC
AUID- ORCID: 0000-0001-8601-8452
AD  - Laboratorio de Desenvolvimento de Vacinas, Instituto Butantan, Sao Paulo, Brazil.
FAU - Rodriguez, Dunia
AU  - Rodriguez D
AD  - Laboratorio de Desenvolvimento de Vacinas, Instituto Butantan, Sao Paulo, Brazil.
FAU - Pancakova, Violeta
AU  - Pancakova V
AD  - Laboratorio de Desenvolvimento de Vacinas, Instituto Butantan, Sao Paulo, Brazil.
AD  - Universite Claude Bernard Lyon 1 (UCBL1), Villeurbanne, 69100, France.
FAU - Trentini, Monalisa
AU  - Trentini M
AD  - Laboratorio de Desenvolvimento de Vacinas, Instituto Butantan, Sao Paulo, Brazil.
FAU - Faquim-Mauro, Eliana L
AU  - Faquim-Mauro EL
AUID- ORCID: 0000-0001-8083-4272
AD  - Laboratorio de Imunopatologia, Instituto Butantan, Sao Paulo, Brazil.
FAU - Freitas, Amanda P
AU  - Freitas AP
AD  - Laboratorio de Imunopatologia, Instituto Butantan, Sao Paulo, Brazil.
FAU - Khouri, Mariana I
AU  - Khouri MI
AUID- ORCID: 0000-0003-4371-4241
AD  - Laboratorio de Biomarcadores e Inflamacao, Instituto Goncalo Moniz, Fundacao 
      Oswaldo Cruz, Salvador, Brazil.
FAU - Lobo-Silva, Jessica
AU  - Lobo-Silva J
AD  - Laboratorio de Biomarcadores e Inflamacao, Instituto Goncalo Moniz, Fundacao 
      Oswaldo Cruz, Salvador, Brazil.
FAU - Goncalves, Viviane M
AU  - Goncalves VM
AD  - Laboratorio de Desenvolvimento de Vacinas, Instituto Butantan, Sao Paulo, Brazil.
FAU - Schenkman, Rocilda P F
AU  - Schenkman RPF
AD  - Laboratorio de Desenvolvimento de Vacinas, Instituto Butantan, Sao Paulo, Brazil.
FAU - Tanizaki, Martha M
AU  - Tanizaki MM
AD  - Laboratorio de Desenvolvimento de Vacinas, Instituto Butantan, Sao Paulo, Brazil.
FAU - Boraschi, Diana
AU  - Boraschi D
AD  - Istituto di Biochimica e Biologia Cellulare, Consiglio Nazionale delle Ricerche, 
      Napoli, Italy.
AD  - Stazione Zoologica Anton Dohrn, Napoli, Italy.
AD  - Shenzhen Institute of Advanced Technologies (SIAT), Chinese Academy of Sciences 
      (CAS), Shenzhen, China Division of Infectious Diseases, Boston Children's 
      Hospital, Boston, MA, USA.
FAU - Malley, Richard
AU  - Malley R
AD  - Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.
FAU - Farias, Leonardo P
AU  - Farias LP
AD  - Laboratorio de Biomarcadores e Inflamacao, Instituto Goncalo Moniz, Fundacao 
      Oswaldo Cruz, Salvador, Brazil.
FAU - Leite, Luciana C C
AU  - Leite LCC
AD  - Laboratorio de Desenvolvimento de Vacinas, Instituto Butantan, Sao Paulo, Brazil.
LA  - eng
PT  - Journal Article
DEP - 20211022
PL  - New Zealand
TA  - Int J Nanomedicine
JT  - International journal of nanomedicine
JID - 101263847
SB  - IM
MH  - Animals
MH  - Bacterial Outer Membrane
MH  - *Escherichia coli
MH  - Immunity
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Schistosoma mansoni
PMC - PMC8548026
OTO - NOTNLM
OT  - OMV
OT  - Schistosoma mansoni
OT  - TSP-2 antigen
OT  - biotin-avidin coupling
OT  - nanoparticle
OT  - outer membrane vesicles
OT  - vaccine
COIS- The authors MMFB, GB and LCCL have a patent application involving the OMV-Antigen 
      complex. The author RM has several patent applications involving the MAPS 
      technology and is a scientific founder, consultant and board member of Affinivax, 
      a biotechnology company that is developing vaccines using the MAPS technology. Ms 
      Violeta Pancakova report grants from EACEA (Education, Audiovisual and Culture 
      Executive Agency) during the conduct of the study; Dr Richard Malley reports 
      personal fees from Merck Vaccines, grants from Pfizer, grants from Astellas, 
      outside the submitted work; Dr Luciana C C Leite reports grants from FAPESP, 
      non-financial support from Fundacao Butantan, a Fellowship from CNPq, during the 
      conduct of the study. The authors report no other conflicts of interest in this 
      work.
EDAT- 2021/10/30 06:00
MHDA- 2021/11/25 06:00
PMCR- 2021/10/22
CRDT- 2021/10/29 06:23
PHST- 2021/04/22 00:00 [received]
PHST- 2021/09/22 00:00 [accepted]
PHST- 2021/10/29 06:23 [entrez]
PHST- 2021/10/30 06:00 [pubmed]
PHST- 2021/11/25 06:00 [medline]
PHST- 2021/10/22 00:00 [pmc-release]
AID - 315786 [pii]
AID - 10.2147/IJN.S315786 [doi]
PST - epublish
SO  - Int J Nanomedicine. 2021 Oct 22;16:7153-7168. doi: 10.2147/IJN.S315786. 
      eCollection 2021.