Studies of a prophylactic HIV-1 vaccine candidate based on modified vaccinia virus Ankara (MVA) with and without DNA priming: effects of dosage and route on safety and immunogenicity.
BACKGROUND
Two parallel studies evaluated safety and immunogenicity of a prophylactic HIV-1 vaccine in 192 HIV-seronegative, low-risk volunteers. Modified vaccinia virus Ankara (MVA) and plasmid DNA (pTHr) expressed HIV-1 clade A gag p24 and p17 fused to a string of 25 overlapping CD8+ T cell epitopes (HIVA).


METHODS
These studies compared intramuscular, subcutaneous, and intradermal MVA at dosage levels ranging from 5x10(6)-2.5x10(8) pfu. In Study IAVI-010, DNA vaccine was given as a prime at months 0 and 1, followed by MVA as a boost at months 5 and 8. In Study IAVI-011, MVA alone was given at months 0 and 2. Regular safety monitoring was performed. Immunogenicity was measured by the interferon (IFN)-gamma ELISPOT assay on peripheral blood mononuclear cells (PBMC).


RESULTS
No serious adverse events were attributed to either vaccine; most adverse events were mild or moderate, although MVA resulted in some severe local reactions. Five vaccine recipients had at least one positive IFN-gamma ELISPOT response, but none were sustained.


CONCLUSIONS
This HIV-1 vaccine candidate was in general safe and well-tolerated. Local reactions were common, but tolerable. Detectable immune responses were infrequent.
Peters
Barry S
BS
Kings College London, UK. Barry.Peters@kcl.ac.uk
Jaoko
Walter
W
Vardas
Eftyhia
E
Panayotakopoulos
George
G
Fast
Patricia
P
Schmidt
Claudia
C
Gilmour
Jill
J
Bogoshi
Mampedi
M
Omosa-Manyonyi
Gloria
G
Dally
Len
L
Klavinskis
Linda
L
Farah
Bashir
B
Tarragona
Tony
T
Bart
Pierre-Alexandre
PA
Robinson
Andrew
A
Pieterse
Colleen
C
Stevens
Wendy
W
Thomas
Richard
R
Barin
Burc
B
McMichael
Andrew J
AJ
McIntyre
James A
JA
Pantaleo
Giuseppe
G
Hanke
Tomás
T
Bwayo
Job
J
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000009:adverse effects / Q000276:immunology*
D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; C505104:MVA-HIVA vaccine; D019444:Vaccines, DNA; D007371:Interferon-gamma