Broad immunogenicity of a multigene, multiclade HIV-1 DNA vaccine boosted with heterologous HIV-1 recombinant modified vaccinia virus Ankara.
BACKGROUND
A human immunodeficiency virus (HIV) vaccine that limits disease and transmission is urgently needed. This clinical trial evaluated the safety and immunogenicity of an HIV vaccine that combines a plasmid-DNA priming vaccine and a modified vaccinia virus Ankara (MVA) boosting vaccine.


METHODS
Forty healthy volunteers were injected with DNA plasmids containing gp160 of HIV-1 subtypes A, B, and C; rev B; p17/p24 gag A and B, and RTmut B by use of a needle-free injection system. The vaccine was administered intradermally or intramuscularly, with or without recombinant granulocyte macrophage colony-stimulating factor, and boosted with a heterologous MVA containing env, gag, and pol of CRF01A_E. Immune responses were monitored with HIV-specific interferon (IFN)-gamma and interleukin (IL)-2 ELISpot and lymphoproliferative assays (LPAs).


RESULTS
Vaccine-related adverse events were mild and tolerable. After receipt of the DNA priming vaccine, 11 (30%) of 37 vaccinees had HIV-specific IFN-gamma responses. After receipt of the MVA boosting vaccine, ELISpot assays showed that 34 (92%) of 37 vaccinees had HIV-specific IFN-gamma responses, 32 (86%) to Gag and 24 (65%) to Env. IFN-gamma production was detected in both the CD8(+) T cell compartment (5 of 9 selected vaccinees) and the CD4(+) T cell compartment (9 of 9). ELISpot results showed that 25 (68%) of 37 vaccinees had a positive IL-2 response and 35 (92%) of 38 had a positive LPA response. Of 38 subjects, a total of 37 (97%) were responders. One milligram of HIV-1 DNA administered intradermally was as effective as 4 mg administered intramuscularly in priming for the MVA boosting vaccine.


CONCLUSIONS
This HIV-DNA priming-MVA boosting approach is safe and highly immunogenic.


BACKGROUND
International Standard Randomised Controlled Trial number: ISRCTN32604572 .
Sandström
Eric
E
Department of Clinical Science and Education, Södersjukhuset, Sweden. Eric.sandstrom@sodersjukhuset.se
Nilsson
Charlotta
C
Hejdeman
Bo
B
Bråve
Andreas
A
Bratt
Göran
G
Robb
Merlin
M
Cox
Josephine
J
Vancott
Thomas
T
Marovich
Mary
M
Stout
Richard
R
Aboud
Said
S
Bakari
Muhammad
M
Pallangyo
Kisali
K
Ljungberg
Karl
K
Moss
Bernard
B
Earl
Patricia
P
Michael
Nelson
N
Birx
Deborah
D
Mhalu
Fred
F
Wahren
Britta
B
Biberfeld
Gunnel
G
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000592:standards*; D000328:Adult; D000917:Antibody Formation / Q000276:immunology; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000009:adverse effects / Q000235:genetics / Q000276:immunology* / Q000592:standards*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
D016915:AIDS Vaccines; D019444:Vaccines, DNA