Abstract:
Background
Intradermal priming with DNA prior to MVA boosts gives
strong and broad immunogenicity, however that required
5 injections at each immunization. A higher concentration
of DNA might allow a simpler administration.
Methods
This double blind, placebo-controlled trial, enrolled 120
(12 placebo) HIV-uninfected volunteers, in Dar es Salaam
and Mbeya. Two pools of DNA plasmids were used (pool1
EnvABC + RevB, pool2 GagAB + RTB) boosted with
MVA CMDR EnvE, GagA, PolA. Volunteers were randomized
in three groups of 40, primed with either two injections
of 300ug, one in each arm, (total 600ug) of DNA
with combined plasmids (group IA) or two injections of
300ug with one pool in each arm (total 600ug) of DNA
(group IIA) “simplified regimens” or five injections,
2 (pool1) and 3 (pool2) injections in the right and left arm
respectively, (total 1000ug) of DNA (IIIA) “standard regimen”.
DNA/Placebo priming was administered by a needlefree
(Biojector) device intradermally at weeks 0, 4 and
12. All volunteers were boosted intramuscularly with
10 pfu of recombinant MVA/placebo at weeks 30 and 46.
The primary end point was the number of ELISpot
responders to Gag and Env, 2 weeks post the last
vaccination.
esults
There were no safety concerns. The response rate to Gag
and/or Env was 27/32 (84%) in group IA vs 31/33 (94%) in
group IIA (p=0.26). The response rate to Gag and/or Env
when comparing the ‘simplified regimens’ vs ‘standard’
regimen was 58/65 (89%) vs 32/32 (100%) p=0.09. In
responders the median magnitude (IQR) response to Gag
was 165 (100,365) SFC/million PBMC vs 210 (120,320),
p=0.46 while the magnitude for Env was 150 (92,225) vs
110 (80,160) p=0.17 for the ‘simplified’ vs ‘standard’
regimens.
Conclusion
The simplified HIV-1 DNA regimens primed as well as
the standard regimen for cellular immune responses following
boosting with with MVA.
