Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

NK cell immune responses differ after prime and boost vaccination

ABSTRACT: A better understanding of innate responses induced by vaccination is critical for designing optimal vaccines. Here, we studied the diversity and dynamics of the NK cell compartment after prime-boost immunization with the modified vaccinia virus Ankara using cynomolgus macaques as a model. Mass cytometry was used to deeply characterize blood NK cells. The NK cell subphenotype composition was modified by the prime. Certain phenotypic changes induced by the prime were maintained over time and, as a result, the NK cell composition prior to boost differed from that before prime. The key phenotypic signature that distinguished NK cells responding to the boost from those responding to the prime included stronger expression of several cytotoxic, homing, and adhesion molecules, suggesting that NK cells at recall were functionally distinct. Our data reveal potential priming or imprinting of NK cells after the first vaccine injection. This study provides novel insights into prime-boost vaccination protocols that could be used to optimize future vaccines.

ORGANISM(S): Macaca fascicularis

SUBMITTER: Anne-Sophie Beignon

PROVIDER: E-MTAB-7697 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:Successful development of HIV-vaccination strategies will also depend on the ability to use novel approaches to analyse and integrate immunogenicity data generated in vaccine trials. The ANRS VAC 18 trial evaluated the immunogenicity of HIV-LIPO-5 vaccine (5 HIV peptides coupled to a palmytoil tail) administered at W0, 4, 12 and 24 in healthy volunteers. 62-69% of vaccinees developed HIV-specific ELISpot responses by W26. Here we present extensive immunogenicity assessments in a subset of vaccinees using ELISpot, lymphoproliferation, intracellular cytokine staining (ICS), cytokine multiplex and transcriptomic analyses. Peripheral blood mononuclear cells from volunteers collected before and following vaccinations were stimulated with HIV LIPO 5 vaccine, Gag peptides contained or not in the vaccine as controls. Different time points and stimulation conditions were compared, using false discovery rate to control for test multiplicity. 74% and 30% of vaccinees had cultured ELISpot and lymphoproliferation responses at W14, respectively. Ex-vivo ICS showed mainly single IL-2 producing cells. Secretion of IFN-Î³, TNF-Î±, IL-5, and IL-13 increased significantly in response to Gag stimulation after culture at W14 compared to W0. An induction of metallothionein genes was consistently detected after HIV-LIPO-5 stimulation at W0 and W14 related to the adjuvant effect of the lipid tail. After vaccination (W14), significant probes increased substantially (>1200 probes) including IFN-Î³, CXCL9, IL2RA, TNFAIP6, CCL3L1 and IL-6 W14 (fold change > 100%). In conclusion, HIV LIPO-5 vaccination elicited memory precursor responses with a Th1 and Th2 profile. The signature profile before vaccination provides information about the adjuvant effect of the lipid tail. Consistently with cytokine responses, vaccination is associated with a modulation in gene expression. This combined approach allowed to identify new signatures of HIV vaccine response and indicates that HIV-LIPO-5 could be further developed as a prime component of heterologous prime boost strategies. PBMC mRNA of 12 healthy volunteers, stimulate in four different conditions (HIV-LIPO-5, Gag+, Gag-, NS) during 6 and 24 hours before and after vaccination (week 0 and week 14)

Project description:Using whole-blood transcriptional profiling, we investigated differences in the host response to vaccination and challenge in a rhesus macaque AIDS vaccine trial. Samples were collected from animals prior to and after vaccination with live irradiated vaccine cells secreting the modified endoplasmic reticulum chaperone gp96-Ig loaded with SIV peptides, either alone or in combination with a SIV-gp120 protein boost. Additional samples were collected following multiple low-dose rectal challenge with SIVmac251. Animals in the boosted group had a 73% reduced risk of infection. Surprisingly, few changes in gene expression were observed during the vaccination phase. Focusing on post-challenge comparisons, in particular for protected animals, we identified a host response signature of protection comprised of strong interferon signaling after the first challenge, which then largely abated after further challenges. We also identified a host response signature, comprised of early macrophage-mediated inflammatory responses, in animals with undetectable viral load five days after the first challenge, but which had unusually high viral titers after subsequent challenges. Statistical analysis showed that prime-boost vaccination significantly lowered the probability of infection in a time-consistent manner throughout several challenges. Given that humoral responses in the prime-boost group were highly significant pre-challenge correlates of protection, the strong innate signaling after the first challenge suggests that interferon signaling enhances vaccine-induced antibody responses and is an important contributor to protection from infection during repeated low-dose exposure to SIV. 36 Indian-origin outbred, young adult, male and female rhesus macaques divided into thre vaccination groups of 12 animals each. Groups were balanced for Mamu-A*01 (three in each group), Mamu-B*08 (one in each group), and for susceptible and resistant TRIM5α alleles. There were no Mamu-B*17+ animals. The prime group (PG) received Gp96 SIV Ig vaccine 292 cells that were transfected with plasmids encoding gp96-Ig, SIVmac251 rev-tat-nef, Gag and gp160 (35). They were injected intraperitoneally with 107 irradiated gp96SIVIg vaccine cells in HBSS, which secrete 10 μg of gp96SIVIg per 24 h. For the prime-boost group (PBG), 100 g of rSIVgp120 protein was added to the vaccine cells. The control group received 292-gp96 Ig cells not transfected with SIV antigens. After a 32-week vaccination phase, which consisted of priming in weeks 0, 6, and 25 and (for the PBG only) additional boosts in weeks 6 and 25, all animals were subject to up to seven weekly low-dose intrarectal challenges starting at 33-week with SIVmac251 at a dosage of 120 TCID50. Whenever an animal had detectable viral load (>50 copies/ml of plasma) at 5 days post challenge, it was considered viremic, further challenges were suspended, and only viral load screening continued on a weekly basis. Whole blood samples (preserved in PAXgene tubes) were collected 2 weeks prior to the first prime, 1 week after the first prime, 2 weeks before and 1 week after the third prime, 1 week before the first challenge, for newly infected animals five days into the corresponding study week and from viremic animals four days into the study week (also denoted as challenge 2 and challenge 3). Total RNA was isolated from Paxgene tubes using Paxgene Blood RNeasy Mini Kits (Qiagen) following the manufacturer’s protocol. RNA quality was assessed on an Agilent 2100 Bioanalyzer using the nanochip format, and only intact RNA was used for microarray analyses.

Dataset Information

NK cell immune responses differ after prime and boost vaccination

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure