Characterization of human immunodeficiency virus Gag-specific gamma interferon-expressing cells following protective mucosal immunization with alphavirus replicon particles.
A safe, replication-defective viral vector that can induce mucosal and systemic immune responses and confer protection against many infectious pathogens, such as human immunodeficiency virus type 1 (HIV-1), may be an ideal vaccine platform. Accordingly, we have generated and tested alphavirus replicon particles encoding HIV-1 Gag from Sindbis virus (SIN-Gag) and Venezuelan equine encephalitis virus (VEE-Gag), as well as chimeras between the two (VEE/SIN-Gag). Following intramuscular (i.m.), intranasal (i.n.), or intravaginal (IVAG) immunization with VEE/SIN-Gag and an IVAG challenge with vaccinia virus encoding HIV Gag (VV-Gag), a larger number of Gag-specific CD8+ intracellular gamma interferon-expressing cells (iIFNEC) were detected in iliac lymph nodes (ILN), which drain the vaginal/uterine mucosa (VUM), than were observed after immunizations with SIN-Gag. Moreover, a single i.n. or IVAG immunization with VEE/SIN-Gag induced a larger number of cells expressing HIV Gag in ILN, and immunizations with VEE/SIN-Gag through any route induced better protective responses than immunizations with SIN-Gag. In VUM, a larger percentage of iIFNEC expressed alpha4beta7 or alpha(Ebeta)7 integrin than expressed CD62L integrin. However, in spleens (SP), a larger percentage of iIFNEC expressed alpha4beta7 or CD62L than expressed alpha(Ebeta)7. Moreover, a larger percentage of iIFNEC expressed the chemokine receptor CCR5 in VUM and ILN than in SP. These results demonstrate a better induction of cellular and protective responses following immunizations with VEE/SIN-Gag than that following immunizations with SIN-Gag and also indicate a differential expression of homing and chemokine receptors on iIFNEC in mucosal effector and inductive sites versus systemic lymphoid tissues.
Gupta
Soumi
S
Department of Pathology and Center for Comparative Medicine, University of California, Davis, USA.
Janani
Ramesh
R
Bin
Qian
Q
Luciw
Paul
P
Greer
Catherine
C
Perri
Silvia
S
Legg
Harold
H
Donnelly
John
J
Barnett
Susan
S
O'Hagan
Derek
D
Polo
John M
JM
Vajdy
Michael
M
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002678:Chimera / Q000235:genetics; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics; D005260:Female; D015683:Gene Products, gag / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D015750:Genes, gag; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D018928:Immunity, Mucosal; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D019713:Receptors, CCR5 / Q000096:biosynthesis; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis; D012093:Replicon; D012845:Sindbis Virus / Q000235:genetics
D015683:Gene Products, gag; D019713:Receptors, CCR5; D016201:Receptors, Lymphocyte Homing; D007371:Interferon-gamma