PMID- 10390545
OWN - NLM
STAT- MEDLINE
DCOM- 19990817
LR  - 20181113
IS  - 1076-1551 (Print)
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Linking)
VI  - 5
IP  - 5
DP  - 1999 May
TI  - Route and method of delivery of DNA vaccine influence immune responses in mice 
      and non-human primates.
PG  - 287-300
AB  - BACKGROUND: In spite of the large number of studies that have evaluated DNA-based 
      immunization, few have directly compared the immune responses generated by 
      different routes of immunization, particularly in non-human primates. Here we 
      examine the ability of a hepatitis B surface antigen (HBsAg)-encoding plasmid to 
      induce immune responses in mice and non-human primates (rhesus monkeys: Macaca 
      mulatta) after delivery by a number of routes. MATERIALS AND METHODS: Eight 
      different injected [intraperitoneal (IP), intradermal (ID), intravenous (IV), 
      intramuscular (IM), intraperineal (IPER), subcutaneous (SC), sublingual (SL), 
      vaginal wall (VW)] and six noninjected [intranasal inhalation (INH), intranasal 
      instillation (INS), intrarectal (IR), intravaginal (IVAG), ocular (Oc), oral 
      feeding (oral)] routes and the gene gun (GG) were used to deliver 
      HBsAg-expressing plasmid DNA to BALB/c mice. Sera were assessed for 
      HBsAg-specific antibodies (anti-HBs, IgG, IgG1, IgG2a) and cytotoxic T lymphocyte 
      (CTL) activity measured. Three of the most commonly used routes (IM, ID, GG) were 
      compared in rhesus monkeys, also using HBsAg-expressing vectors. Monkeys were 
      immunized with short (0-, 4- and 8-week) or long (0-, 12- and 24-week) intervals 
      between boosts, and in the case of GG, also with different doses, and their sera 
      were assessed for anti-HBs. RESULTS: In one study, anti-HBs were detected in 
      plasma of mice treated by five of eight of the injected and none of the six 
      noninjected routes. The highest levels of anti-HBs were induced by IM and IV 
      injections, although significant titers were also obtained with SL and ID. Each 
      of these routes also induced CTL, as did IPER and VW and one noninjected route 
      (INH) that failed to induce antibodies. In a second study, GG (1.6 microg) was 
      compared to ID and IM (100 microg) delivery. Significant titers were obtained by 
      all routes after only one boost, with the highest levels detected by IM. Delivery 
      to the skin by GG induced exclusively IgG1 antibodies (Th2-like) at 4 weeks and 
      only very low IgG2a levels at later times; ID-immunized mice had predominantly 
      IgG1 at 4 weeks and this changed to mixed IgG1/IgG2a over time. Responses with IM 
      injection (in the leg or tongue) were predominantly IgG2a (Th1-like) at all 
      times. IV injection gave mixed IgG1/IgG2a responses. In monkeys, in the first 
      experiment, 1 mg DNA IM or ID at 0, 4, and 8 weeks gave equivalent anti-HB titers 
      and 0.4 microg at the same times by GG induced lower titers. In the second 
      experiment, 1 mg DNA IM or ID, or 3.2 microg by GG, at 0, 12, and 24 weeks, gave 
      anti-HB values in the hierarchy of GG > IM > ID. Furthermore, high titers were 
      retained after a single immunization in mice but fell off over time in the 
      monkeys, even after boost. CONCLUSIONS: Route of administration of plasmid DNA 
      vaccines influences the strength and nature of immune responses in mice and 
      non-human primates. However, the results in mice were not always predictive of 
      those in monkeys and this is likely true for humans as well. Optimal dose and 
      immunization schedule will most likely vary between species. It is not clear 
      whether results in non-human primates will be predictive of results in humans, 
      thus additional studies are required. 
      http://link.springer-ny.com/link/service/journals/00020/bibs /5n5p287. html
FAU - McCluskie, M J
AU  - McCluskie MJ
AD  - Loeb Health Research Institute at the Ottawa Hospital, Ottawa, Canada.
FAU - Brazolot Millan, C L
AU  - Brazolot Millan CL
FAU - Gramzinski, R A
AU  - Gramzinski RA
FAU - Robinson, H L
AU  - Robinson HL
FAU - Santoro, J C
AU  - Santoro JC
FAU - Fuller, J T
AU  - Fuller JT
FAU - Widera, G
AU  - Widera G
FAU - Haynes, J R
AU  - Haynes JR
FAU - Purcell, R H
AU  - Purcell RH
FAU - Davis, H L
AU  - Davis HL
LA  - eng
GR  - N01-AI-52705/AI/NIAID NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 0 (Hepatitis B Surface Antigens)
RN  - 0 (Hepatitis B Vaccines)
RN  - 0 (Vaccines, DNA)
SB  - IM
MH  - Administration, Cutaneous
MH  - Administration, Intranasal
MH  - Administration, Oral
MH  - Animals
MH  - Antibody Formation
MH  - Female
MH  - Hepatitis B Surface Antigens/genetics/immunology
MH  - Hepatitis B Vaccines/*administration & dosage/*immunology
MH  - Immunity, Cellular
MH  - Injections, Intramuscular
MH  - Injections, Intravenous
MH  - Macaca mulatta
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Predictive Value of Tests
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Time Factors
MH  - Vaccines, DNA/*administration & dosage
PMC - PMC2230426
EDAT- 1999/07/03 00:00
MHDA- 1999/07/03 00:01
PMCR- 1999/05/01
CRDT- 1999/07/03 00:00
PHST- 1999/07/03 00:00 [pubmed]
PHST- 1999/07/03 00:01 [medline]
PHST- 1999/07/03 00:00 [entrez]
PHST- 1999/05/01 00:00 [pmc-release]
AID - 0126 [pii]
PST - ppublish
SO  - Mol Med. 1999 May;5(5):287-300.