PMID- 12551699
OWN - NLM
STAT- MEDLINE
DCOM- 20030926
LR  - 20191106
IS  - 0939-6411 (Print)
IS  - 0939-6411 (Linking)
VI  - 55
IP  - 1
DP  - 2003 Jan
TI  - The effect of co-administration of adjuvants with a nanoparticle-based genetic 
      vaccine delivery system on the resulting immune responses.
PG  - 11-8
AB  - Previously, we reported on a novel cationic nanoparticle-based DNA vaccine 
      delivery system. In the present studies, the effects of co-administration of two 
      well-known adjuvants, cholera toxin (CT) and lipid A (LA), with plasmid DNA 
      (pDNA)-coated nanoparticles were investigated. Balb/C mice (n=6) were immunized 
      with either pDNA alone (cytomegalovirus-beta-galactosidase, 5 microg) or 
      pDNA-coated nanoparticles with either 0 or 50 microg of LA on days 0, 7, and 14 
      subcutaneously (s.c.), or topically on shaved skin with either pDNA (5 microg) 
      alone or pDNA-coated nanoparticles with 0, 10, or 100 microg of CT on days 0, 6, 
      21, and 35. Mice were sacrificed on day 28 or day 45. Serum IgG titer, in vitro 
      cytokine release and cell proliferation of the isolated splenocytes were 
      determined. By the topical route, immunization of mice with 'naked' pDNA together 
      with 10 and 100 microg of CT significantly enhanced the antigen-specific serum 
      IgG titer by four- and 20-fold, respectively, compared to immunization with pDNA 
      alone. Moreover, co-administration of 100 microg CT with the pDNA-nanoparticles 
      enhanced the IgG titer by more than 300-fold over immunization with 'naked' pDNA 
      alone with no CT. In vitro interferon-gamma (IFN)-gamma release from splenocytes 
      isolated from mice immunized with pDNA-coated nanoparticles with CT (100 microg) 
      was increased by three-fold over immunization with pDNA-nanoparticles without CT. 
      Similarly, in vitro IFN-gamma release from splenocytes isolated from mice 
      immunized with 'naked' pDNA with CT (100 microg) was increased by two-fold over 
      immunization with 'naked' pDNA without CT. Finally, pDNA-coated nanoparticles 
      adjuvanted with 10 microg CT resulted in the strongest splenocyte proliferation. 
      By the s.c. route, co-administration of LA (50 microg) with pDNA resulted in more 
      than 16-fold enhancement in IgG titer over immunization with 'naked' pDNA alone. 
      Immunization with pDNA-coated nanoparticles with LA (50 microg) led to 16-fold 
      enhancement in specific serum IgG titer over immunization with pDNA-coated 
      nanoparticles with no LA, and more than 250-fold enhancement over immunization 
      with 'naked' pDNA alone with no LA. Moreover, in vitro IFN-gamma release and 
      proliferation by splenocytes isolated from LA co-immunized mice was also 
      significantly enhanced. In conclusion, CT (topical) and LA (s.c.) are potential 
      adjuvants to further enhance immune responses using a novel cationic 
      nanoparticle-based DNA vaccine delivery system.
FAU - Cui, Zhengrong
AU  - Cui Z
AD  - Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 
      Lexington, KY 40536, USA.
FAU - Mumper, Russell J
AU  - Mumper RJ
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Eur J Pharm Biopharm
JT  - European journal of pharmaceutics and biopharmaceutics : official journal of 
      Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
JID - 9109778
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Lipid A)
RN  - 0 (Vaccines, DNA)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9012-63-9 (Cholera Toxin)
SB  - IM
MH  - Adjuvants, Immunologic/*administration & dosage/pharmacology
MH  - Administration, Topical
MH  - Animals
MH  - Cell Division
MH  - Cells, Cultured
MH  - Cholera Toxin/administration & dosage/immunology
MH  - Dose-Response Relationship, Drug
MH  - *Drug Delivery Systems
MH  - Drug Synergism
MH  - Female
MH  - Immunoglobulin G/blood
MH  - Injections, Subcutaneous
MH  - Interferon-gamma/blood
MH  - Lipid A/immunology/*pharmacology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Nanotechnology
MH  - Particle Size
MH  - Plasmids
MH  - Spleen/cytology/immunology
MH  - Vaccines, DNA/*immunology
EDAT- 2003/01/29 04:00
MHDA- 2003/09/27 05:00
CRDT- 2003/01/29 04:00
PHST- 2003/01/29 04:00 [pubmed]
PHST- 2003/09/27 05:00 [medline]
PHST- 2003/01/29 04:00 [entrez]
AID - S0939641102001297 [pii]
AID - 10.1016/s0939-6411(02)00129-7 [doi]
PST - ppublish
SO  - Eur J Pharm Biopharm. 2003 Jan;55(1):11-8. doi: 10.1016/s0939-6411(02)00129-7.