Safety, immunogenicity and efficacy of peptide-pulsed cellular immunotherapy in macaques.
BACKGROUND
Simple and effective delivery methods for cellular immunotherapies are needed. We recently published on the effectiveness of using ex vivo pulsing of overlapping SIV Gag 15mer peptides onto fresh peripheral blood cells in 32 SIV(mac251)-infected pigtail macaques.


METHODS
We now report on the safety of this approach, analysis of a novel assay for immunogenicity, the effect of an MHC allele, Mane-A*10, on CD8 T cell escape occurring and disease outcome.


RESULTS
The vaccine strategy was safe, with no perturbations in weight or hematological profiles in comparison to controls. The high levels of SIV-specific T cell immunogenicity of this approach was confirmed using a novel assay measuring upregulation of surface CD134 of CD4 T cells. A substantial effect of the Mane-A*10 allele in reducing SIV viral load of pigtail macaques was observed in both vaccinees and controls; the virologic efficacy of the immunotherapy in comparison to controls was greatest in Mane-A*10- animals. Escape mutations at several new CD8 T cell epitopes throughout the SIV proteome were observed, primarily in animals with poorer virologic control.


CONCLUSIONS
In summary, we provide further information that peptide-pulsed PBMC are a safe, immunogenic and effective immunotherapy. The observed influence of MHC alleles and immune escape allows us to design more insightful future immunotherapy studies.
De Rose
Robert
R
Department of Microbiology and Immunology, University of Melbourne, Australia.
Mason
Rosemarie D
RD
Loh
Liyen
L
Peut
Viv
V
Smith
Miranda Z
MZ
Fernandez
Caroline S
CS
Alcantara
Sheilajen
S
Amarasena
Thakshila
T
Reece
Jeanette
J
Seddiki
Nabila
N
Kelleher
Anthony D
AD
Zaunders
John
J
Kent
Stephen J
SJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008254:Macaca nemestrina; D010455:Peptides / Q000276:immunology; D053262:Receptors, OX40 / Q000378:metabolism; D017422:Sequence Analysis, DNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000628:therapy*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D016896:Treatment Outcome
D010455:Peptides; D053262:Receptors, OX40